H. Lee Moffitt Cancer Center & Research Institute

Find a Researcher

Said M. Sebti, PhD

Said M. Sebti, PhD

Faculty Rank:

Senior Member

Titles:

  • Program Leader, Drug Discovery Program
  • Chair, Department of Drug Discovery

Department/Program Affiliations:

  • Drug Discovery  

Primary Address:

H. Lee Moffitt Cancer Center &
Research Institute
12902 Magnolia Drive
Tampa, FL 33612

Office:

(813) 745-6734

USF Affiliations/College Department:

  • Medicine / Oncologic Sciences
  • Medicine / Molecular Medicine
  • Medicine / Molecular Pharmacology & Physiology

University Academic Rank:

Professor

For corrections, please e-mail a request

Printer friendly version
Printer friendly version (including publications)

Said M. Sebti, PhD

Education & Training:

  • B.S., Washington State University, Pullman, WA, 1980 - Biochemistry
  • Ph.D., Purdue University, Lafayette, IN, 1984 - Biochemistry
  • Postdoc, Yale University, New Haven, CT, 1987 - Pharmacology

For corrections, please e-mail a request

Printer friendly version
Printer friendly version (including publications)

Said M. Sebti, PhD

Research Interests:

To develop novel anticancer drugs based on targeting growth factor signal transduction, cell cycle, angiogenesis and apoptosis pathways; of particular interest is the role of ras protein in receptor tyrosine kinase signal transduction; key molecules that are presently targeted are farnesyltransferase, geranylgeranyltransferase, STAT3, VEGF, EGF and PDGF and their receptors, proteasome, cyclin-dependent kinases, Bcl2, Mek and Akt.

Key words: Drug discovery, signal transduction, growth factors, farnesyltransferase, geranylgeranyltransferase, myristyltransferase, Ras, Rac, Rho, Raf, MAPK, CDKs, CDIs, cyclins, Bcl2, STATs and peptidomimetics.



For corrections, please e-mail a request

Printer friendly version
Printer friendly version (including publications)

Said M. Sebti, PhD

Publications:

  1. Berndt N, Yang H, Trinczek B, Betzi S, Zhang Z, Wu B, Lawrence NJ, Pellecchia M, Sch?nbrunn E, Cheng JQ, Sebti SM. The Akt activation inhibitor TCN-P inhibits Akt phosphorylation by binding to the PH domain of Akt and blocking its recruitment to the plasma membrane. Cell Death Differ. 2010 May;. Pubmedid: 20489726.   Pubmed ID: 20489726

  2. Chen L, Pernazza D, Scott LM, Lawrence HR, Ren Y, Luo Y, Wu X, Sung SS, Guida WC, Sebti SM, Lawrence NJ, Wu J. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep;80(6):801-810. Pubmedid: 20510203. Pmcid: PMC2906681.   Pubmed ID: 20510203

  3. Garrett CR, Coppola D, Wenham RM, Cubitt CL, Neuger AM, Frost TJ, Lush RM, Sullivan DM, Cheng JQ, Sebti SM. Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT. Invest New Drugs. 2010 Jul. Pubmedid: 20644979.   Pubmed ID: 20644979

  4. Hidalgo-Carrillo J, Sebti J, Aramend?a MA, Marinas A, Marinas JM, Sebti S, Urbano FJ. A study on the potential application of natural phosphate in photocatalytic processes. J Colloid Interface Sci. 2010 Apr;344(2):475-481. Pubmedid: 20129616.   Pubmed ID: 20129616

  5. Kim D, Sun M, He L, Zhou QH, Chen J, Sun XM, Bepler G, Sebti SM, Cheng JQ. A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation. J Biol Chem. 2010 Mar;285(11):8383-8394. Pubmedid: 20068047. Pmcid: PMC2832988.   Pubmed ID: 20068047

  6. Lawrence HR, Kazi A, Luo Y, Kendig R, Ge Y, Jain S, Daniel K, Santiago D, Guida WC, Sebti SM. Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors. Bioorg Med Chem. 2010 Aug;18(15):5576-5592. Pubmedid: 20621484.   Pubmed ID: 20621484

  7. Mahajan K, Coppola D, Challa S, Fang B, Chen YA, Zhu W, Lopez AS, Koomen J, Engelman RW, Rivera C, Muraoka-Cook RS, Cheng JQ, Sch?nbrunn E, Sebti SM, Earp HS, Mahajan NP. Ack1 Mediated AKT/PKB Tyrosine 176 Phosphorylation Regulates Its Activation. PLoS One. 2010;5(3):e9646-. Pubmedid: 20333297.   Pubmed ID: 20333297

  8. Phan J, Li Z, Kasprzak A, Li B, Sebti S, Guida W, Sch?nbrunn E, Chen J. Structure-based design of high affinity peptides inhibiting the interaction of p53 with MDM2 and MDMX. J Biol Chem. 2010 Jan;285(3):2174-2183. Pubmedid: 19910468. Pmcid: PMC2804373.   Pubmed ID: 19910468

  9. Hast MA, Fletcher S, Cummings CG, Pusateri EE, Blaskovich MA, Rivas K, Gelb MH, Van Voorhis WC, Sebti SM, Hamilton AD, Beese LS. Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase. Chem Biol. 2009 Feb;16(2):181-192. Pubmedid: 19246009. Pmcid: PMC2671474.   Pubmed ID: 19246009

  10. Hong DS, Sebti SM, Newman RA, Blaskovich MA, Ye L, Gagel RF, Moulder S, Wheler JJ, Naing A, Tannir NM, Ng CS, Sherman SI, El Naggar AK, Khan R, Trent J, Wright JJ, Kurzrock R. Phase I trial of a combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in advanced malignancies. Clin Cancer Res. 2009 Nov;15(22):7061-7068. Pubmedid: 19903778.   Pubmed ID: 19903778

  11. Husain K, Francois RA, Hutchinson SZ, Neuger AM, Lush R, Coppola D, Sebti S, Malafa MP. Vitamin E delta-tocotrienol levels in tumor and pancreatic tissue of mice after oral administration. Pharmacology. 2009;83(3):157-163. Pubmedid: 19142032. Pmcid: PMC2834260.   Pubmed ID: 19142032

  12. Kayser-Bricker KJ, Glenn MP, Lee SH, Sebti SM, Cheng JQ, Hamilton AD. Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents. Bioorg Med Chem. 2009 Feb;17(4):1764-1771. Pubmedid: 19179081.   Pubmed ID: 19179081

  13. Kazi A, Carie A, Blaskovich MA, Bucher C, Thai V, Moulder S, Peng H, Carrico D, Pusateri E, Pledger WJ, Berndt N, Hamilton A, Sebti SM. Blockade of protein geranylgeranylation inhibits Cdk2-dependent p27Kip1 phosphorylation on Thr187 and Accumulates p27Kip1 in the nucleus: implications for breast cancer therapy. Mol Cell Biol. 2009 Apr;29(8):2254-2263. Pubmedid: 19204084.   Pubmed ID: 19204084

  14. Kazi A, Lawrence H, Guida WC, McLaughlin ML, Springett GM, Berndt N, Yip RM, Sebti SM. Discovery of a novel proteasome inhibitor selective for cancer cells over non-transformed cells. Cell Cycle. 2009 Jun;8(12):1940-1951. Pubmedid: 19471122. Pmcid: PMC2892826.   Pubmed ID: 19471122

  15. Lawrence HR, Li Z, Yip ML, Sung SS, Lawrence NJ, McLaughlin ML, McManus GJ, Zaworotko MJ, Sebti SM, Chen J, Guida WC. Identification of a disruptor of the MDM2-p53 protein-protein interaction facilitated by high-throughput in silico docking. Bioorg Med Chem Lett. 2009 Jul;19(14):3756-3759. Pubmedid: 19457663. Pmcid: PMC2754843.   Pubmed ID: 19457663

  16. Sparano JA, Moulder S, Kazi A, Coppola D, Negassa A, Vahdat L, Li T, Pellegrino C, Fineberg S, Munster P, Malafa M, Lee D, Hoschander S, Hopkins U, Hershman D, Wright JJ, Kleer C, Merajver S, Sebti SM. Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer. Clin Cancer Res. 2009 Apr;15(8):2942-2948. Pubmedid: 19351752. Pmcid: PMC2785076.   Pubmed ID: 19351752

  17. Wei J, Kitada S, Rega MF, Emdadi A, Yuan H, Cellitti J, Stebbins JL, Zhai D, Sun J, Yang L, Dahl R, Zhang Z, Wu B, Wang S, Reed TA, Wang HG, Lawrence N, Sebti S, Reed JC, Pellecchia M. Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins. Mol Cancer Ther. 2009 Apr;8(4):904-913. Pubmedid: 19372563. Pmcid: PMC2750823.   Pubmed ID: 19372563

  18. Elahi A, Zhang L, Yeatman T, Gery S, Sebti S, Shibata D. HPP1-mediated tumor suppression requires activation of STAT1 pathways. Int J Cancer. 2008 Apr;122(7):1567-1572. Pubmedid: 18059030.   Pubmed ID: 18059030

  19. Epling-Burnette PK, Sokol L, Chen X, Bai F, Zhou J, Blaskovich MA, Zou J, Painter JS, Edwards TD, Moscinski L, Yoder JA, Djeu JY, Sebti S, Loughran TP, Wei S. Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling. Blood. 2008 Dec;112(12):4694-4698. Pubmedid: 18791165.   Pubmed ID: 18791165

  20. Gunning PT, Glenn MP, Siddiquee KA, Katt WP, Masson E, Sebti SM, Turkson J, Hamilton AD. Targeting protein-protein interactions: suppression of Stat3 dimerization with rationally designed small-molecule, nonpeptidic SH2 domain binders. Chembiochem. 2008 Nov;9(17):2800-2803. Pubmedid: 19006150. Pmcid: PMC2728599.   Pubmed ID: 19006150

  21. Gustafsdottir SM, Wennstrom S, Fredriksson S, Schallmeiner E, Hamilton AD, Sebti SM, Landegren U. Use of proximity ligation to screen for inhibitors of interactions between vascular endothelial growth factor A and its receptors. Clin Chem. 2008 Jul;54(7):1218-1225. Pubmedid: 18499900.   Pubmed ID: 18499900

  22. Kinkade R, Dasgupta P, Carie A, Pernazza D, Carless M, Pillai S, Lawrence N, Sebti S, Chellappan S. A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice. Cancer Res. 2008 May;68(10):3810-3818. Pubmedid: 18483265.   Pubmed ID: 18483265

  23. Kurzrock R, Kantarjian H, Blaskovich M, Bucher C, Verstovsek S, Wright J, Pilat S, Cortes J, Estey E, Giles F, Beran M, Sebti S. Phase I study of alternate-week administration of tipifarnib in patients withmyelodysplastic syndrome. Clin Cancer Res. 2008 Jan;14(2):509-514. Pubmedid: 18223226.   Pubmed ID: 18223226

  24. Lawrence HR, Pireddu R, Chen L, Luo Y, Sung SS, Szymanski AM, Yip ML, Guida WC, Sebti SM, Wu J, Lawrence NJ. Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem. 2008 Aug;51(16):4948-4956. Pubmedid: 18680359.   Pubmed ID: 18680359

  25. Machida S, Usuba K, Blaskovich MA, Yano A, Harada K, Sebti SM, Kato N, Ohkanda J. Module assembly for protein-surface recognition: geranylgeranyltransferase I bivalent inhibitors for simultaneous targeting of interior and exterior protein surfaces. Chemistry. 2008 Feb;14(5):1392-1401. Pubmedid: 18200641.   Pubmed ID: 18200641

  26. Carie A, Sebti S. A chemical biology approach identifies a beta-2 adrenergic receptor agonist that causes human tumor regression by blocking the Raf-1/Mek-1/Erk1/2 pathway. Oncogene. 2007 May;26(26):3777-3788. Pubmedid: 17260025.   Pubmed ID: 17260025

  27. Delarue F, Adnane J, Joshi B, Blaskovich M, Wang D, Hawker J, BizouarnF, Ohkanda J, Zhu K, Hamilton A, Chellappan S, Sebti S. Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Oncogene. 2007 Feb;26(5):633-40. Pubmedid: 16909123.   Pubmed ID: 16909123

  28. Epifano F, Curini M, Genovese S, Blaskovich M, Hamilton A, Sebti S. Prenyloxyphenylpropanoids as novel lead compounds for the selective inhibition of geranylgeranyl transferase I. Bioorg Med Chem Lett. 2007 May;17(9):2639-2642. Pubmedid: 17314046.   Pubmed ID: 17314046

  29. Falsetti SC, Wang DA, Peng H, Carrico D, Cox AD, Der CJ, Hamilton AD, Sebti SM. Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependentgrowth and induce apoptosis, and RalA to inhibit anchorage-independent growth. Mol Cell Biol. 2007 Nov;27(22):8003-8014. Pubmedid: 17875936.   Pubmed ID: 17875936

  30. Gunning P, Katt W, Glenn M, Siddique K, Kim J, Jove R, Sebti S, Turkson J, Hamilton A. Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains. Bioorg Med Chem Lett. 2007 Apr;17(7):1875-1878. Pubmedid: 17336521.   Pubmed ID: 17336521

  31. Kayser KJ, Glenn MP, Sebti SM, Cheng JQ, Hamilton AD. Modifications of the GSK3beta substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics. Bioorg Med Chem Lett. 2007 Apr;17(7):2068-2073.. Pubmedid: 17276059.   Pubmed ID: 17276059

  32. Sagatys E, Garrett CR, Boulware D, Kelley S, Malafa M, Cheng JQ, Sebti S, Coppola D. Activation of the serine/threonine protein kinase Akt during the progression of Barrett neoplasia. Hum Pathol. 2007 Oct;38(10):1526-1531. Pubmedid: 17640711.   Pubmed ID: 17640711

  33. Saglam O, Garrett CR, Boulware D, Sayegh Z, Shibata D, Malafa M, Yeatman T, Cheng JQ, Sebti S, Coppola D. Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia. Clin Colorectal Cancer. 2007 Sep;6(9):652-656. Pubmedid: 17945038.   Pubmed ID: 17945038

  34. Siddiquee K, Gunning P, Glenn M, Katt W, Zhang S, Schroeck C, Sebti S, Jove R, Hamilton A, Turkson J. An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects. Acs Chem Biol. 2007 Dec;2(12):787-798. Pubmedid: 18154266.   Pubmed ID: 18154266

  35. Siddiquee K, Zhang S, Guida WC, Blaskovich MA, Greedy B, Lawrence HR, Yip ML, Jove R, McLaughlin MM, Lawrence NJ, Sebti SM, Turkson J. Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A. 2007 May;104(18):7391-7396. Pubmedid: 17463090.   Pubmed ID: 17463090

  36. Chen L, Sung SS, Yip ML, Lawrence HR, Ren Y, Guida WC, Sebti SM, Lawrence NJ, Wu J. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol. 2006 Aug;70(2):562-570. Pubmedid: 16717135.   Pubmed ID: 16717135

  37. Donapaty S, Louis S, Horvath E, Kun J, Sebti S, Malafa M. RRR-{alpha}-Tocopherol succinate down-regulates oncogenic Ras signaling. Mol Cancer Ther. 2006 Feb;5(2):309-316. Pubmedid: 16505104.   Pubmed ID: 16505104

  38. Glenn MP, Chang SY, Horney C, Rivas K, Yokoyama K, Pusateri EE, Fletcher S, Cummings CG, Buckner FS, Pendyala PR, Chakrabarti D, Sebti SM, Gelb M, VanVoorhis WC, Hamilton AD. Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites. J Med Chem. 2006 Sep;49(19):5710-5727. Pubmedid: 16970397.   Pubmed ID: 16970397

  39. Hu B, Gilkes D, Farooqi B, Sebti S, Chen J. MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin. J Biol Chem. 2006 Nov;281(44):33030-33035. Pubmedid: 16905541.   Pubmed ID: 16905541

  40. Ohkanda J, Strickland C, Blaskovich M, Carrico D, Lockman J, Vogt A, Bucher C, Sun J, Qian Y, Knowles D, Pusateri E, Sebti S, Hamilton A. Structure-based design of imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase. Org Biomol Chem. 2006 Feb;4(3):482-492. Pubmedid: 16446806.   Pubmed ID: 16446806

  41. Peng H, Carrico D, Thai V, Blaskovich M, Bucher C, Pusateri E, Sebti S, Hamilton A. Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I. Org Biomol Chem. 2006 May;4(9):1768-1784. Pubmedid: 16633570.   Pubmed ID: 16633570

  42. Sparano J, Moulder S, Kazi A, Vahdat L, Li T, Pellegrino C, Munster P, Malafa M, Lee D, Hoschander S, Hopkins U, Hershman D, Wright J, Sebti S. Targeted inhibition of farnesyltransferase in locally advanced breast cancer: a phase I and II trial of tipifarnib plus dose-dense doxorubicin and cyclophosphamide. J Clin Oncol. 2006 Jul;24(19):3013-3018. Pubmedid: 16769985.   Pubmed ID: 16769985

  43. Tang D, Park H, Georgescu S, Sebti S, Hamilton A, Galper J. Simvastatin potentiates tumor necrosis factor alpha-mediated apoptosis of humanvascular endothelial cells via the inhibition of the geranylgeranylation ofRhoA. Life Sci. 2006 Aug;79(15):1484-1492. Pubmedid: 16740276.   Pubmed ID: 16740276

  44. Zhou H, Wang DA, Baldini L, Ennis E, Jain R, Carie A, Sebti SM, Hamilton AD. Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation. Org Biomol Chem. 2006 Jun;4(12):2376-2386. Pubmedid: 16763682.   Pubmed ID: 16763682

  45. Carrico D, Blaskovich M, Bucher C, Sebti S, Hamilton A. Design, synthesis, and evaluation of potent and selective benzoyleneurea-based inhibitors of protein geranylgeranyltransferase-I. Bioorg Med Chem. 2005 Feb;13(3):677-688. Pubmedid: 15653335.   Pubmed ID: 15653335

  46. Chen L, Yin H, Farooqi B, Sebti S, Hamilton A, Chen J. p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53. Mol Cancer Ther. 2005 Jun;4(6):1019-1025. Pubmedid: 15956260.   Pubmed ID: 15956260

  47. Cloughesy T, Kuhn J, Robins H, Abrey L, Wen P, Fink K, Lieberman F, Mehta M, Chang S, Yung A, DeAngelis L, Schiff D, Junck L, Groves M, Paquette S, Wright J, Lamborn K, Sebti S, Prados M. Phase I trial of tipifarnib in patients with recurrent malignant glioma takingenzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium. J Clin Oncol. 2005 Aug;23(27):6647-6656. Pubmedid: 16170172.   Pubmed ID: 16170172

  48. Glenn M, Chang S, Hucke O, Verlinde C, Rivas K, Horney C, Yokoyama K, Buckner F, Pendyala P, Chakrabarti D, Gelb M, Van Voorhis W, Sebti S, Hamilton A. Structurally simple farnesyltransferase inhibitors arrest the growth of malaria parasites. Angew Chem Int Ed Engl. 2005 Aug;44(31):4903-4906. Pubmedid: 16007716.   Pubmed ID: 16007716

  49. Guida W, Hamilton A, Crotty J, Sebti S. Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling. J Comput Aided Mol Des. 2005 Dec;19(12):871-85. Pubmedid: 16607571.   Pubmed ID: 16607571

  50. Mazieres J, Tillement V, Allal C, Clanet C, Bobin L, Chen Z, Sebti SM, Favre G, Pradines A. Geranylgeranylated, but not farnesylated, RhoB suppresses Ras transformation of NIH-3T3 cells. Exp Cell Res. 2005 Apr;304(2):354-364. Pubmedid: 15748883.   Pubmed ID: 15748883

  51. Nallan L, Bauer K, Bendale P, Rivas K, Yokoyama K, Horney C, Pendyala P, Floyd D, Lombardo L, Williams D, Hamilton A, Sebti S, Windsor W, Weber P, Buckner F, Chakrabarti D, Gelb M, Van Voorhis W. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J Med Chem. 2005 Jun;48(11):3704-3713. Pubmedid: 15916422.   Pubmed ID: 15916422

  52. Nefedova Y, Cheng P, Gilkes D, Blaskovich M, Beg AA, Sebti SM, Gabrilovich DI. Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J Immunol. 2005 Oct;175(7):4338-4346. Pubmedid: 16177074.   Pubmed ID: 16177074

  53. Nefedova Y, Nagaraj S, Rosenbauer A, Muro-Cacho C, Sebti SM, Gabrilovich DI. Regulation of dendritic cell differentiation and antitumor immune response in cancer by pharmacologic-selective inhibition of the janus-activated kinase 2/signal transducers and activators of transcription 3 pathway. Cancer Res. 2005 Oct;65(20):9525-9535. Pubmedid: 16230418.   Pubmed ID: 16230418

  54. Sebti S. Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy. Cancer Cell. 2005 Apr;7(4):297-300. Pubmedid: 15837619.   Pubmed ID: 15837619

  55. Sun J, Blaskovich MA, Jove R, Livingston SK, Coppola D, Sebti SM. Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene. 2005 May;24(20):3236-3245. Pubmedid: 15735720.   Pubmed ID: 15735720

  56. Sun J, Wang DA, Jain RK, Carie A, Paquette S, Ennis E, Blaskovich MA, Baldini L, Coppola D, Hamilton AD, Sebti SM. Inhibiting angiogenesis and tumorigenesis by a synthetic molecule that blocks binding of both VEGF and PDGF to their receptors. Oncogene. 2005 Jul;24(29):4701-4709. Pubmedid: 15897913.   Pubmed ID: 15897913

  57. Takahashi Y, Karbowski M, Yamaguchi H, Kazi A, Wu J, Sebti SM, Youle RJ, Wang HG. Loss of bif-1 suppresses bax/bak conformational change and mitochondrial apoptosis. Mol Cell Biol. 2005 Nov;25(21):9369-9382. Pubmedid: 16227588.   Pubmed ID: 16227588

  58. Turkson J, Zhang S, Mora LB, Burns A, Sebti S, Jove R. A novel platinum compound that inhibits constitutive Stat3 signaling and induces cell cycle arrest and apoptosis of malignant cells. J Biol Chem. 2005 Sep;280(38):32979-32988. Pubmedid: 16046414.   Pubmed ID: 16046414

  59. Wang D, Sebti S. Palmitoylated cysteine 192 is required for RhoB tumor-suppressive and apoptotic activities. J Biol Chem. 2005 May;280(19):19243-19249. Pubmedid: 15713677.   Pubmed ID: 15713677

  60. Woo J, Nakagawa H, Krecic A, Nagai K, Hamilton A, Sebti S, Stern P. Inhibitory effects of mevastatin and a geranylgeranyl transferase I inhibitor (GGTI-2166) on mononuclear osteoclast formation induced by receptor activator of NF kappa B ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha). Biochem Pharmacol. 2005 Jan;69(1):87-95. Pubmedid: 15588717.   Pubmed ID: 15588717

  61. Yin H, Lee G, Park H, Payne G, Rodriguez J, Sebti S, Hamilton A. Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. Angew Chem Int Ed Engl. 2005 Apr;44(18):2704-2707. Pubmedid: 15765497.   Pubmed ID: 15765497

  62. Yin H, Lee G, Sedey K, Kutzki O, Park H, Orner B, Ernst J, Wang H, Sebti S, Hamilton A. Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL. J Am Chem Soc. 2005 Jul;127(29):10191-10196. Pubmedid: 16028929.   Pubmed ID: 16028929

  63. Yin H, Lee G, Sedey K, Rodriguez J, Wang H, Sebti S, Hamilton A. Terephthalamide derivatives as mimetics of helical peptides: disruption of the Bcl-x(L)/Bak interaction. J Am Chem Soc. 2005 Apr;127(15):5463-5468. Pubmedid: 15826183.   Pubmed ID: 15826183

  64. Zhu K, Gerbino E, Beaupre DM, Mackley PA, Muro-Cacho C, Beam C, Hamilton AD, Lichtenheld MG, Kerr WG, Dalton W, Alsina M, Sebti SM. Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells. Blood. 2005 Jun;105(12):4759-4766. Pubmedid: 15728126.   Pubmed ID: 15728126

  65. Zuckerbraun B, Barbato J, Hamilton A, Sebti S, Tzeng E. Inhibition of geranylgeranyltransferase I decreases generation of vascular reactive oxygen species and increases vascular nitric oxide production. J Surg Res. 2005 Apr;124(2):256-263. Pubmedid: 15820256.   Pubmed ID: 15820256

  66. Alsina M, Fonseca R, Wilson EF, Belle AN, Gerbino E, Price-Troska T, Overton RM, Ahmann G, Bruzek LM, Adjei AA, Kaufmann SH, Wright JJ, Sullivan D, Djulbegovic B, Cantor AB, Greipp PR, Dalton WS, Sebti SM. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Blood. 2004 May;103(9):3271-3277. Pubmedid: 14726402.   Pubmed ID: 14726402

  67. Carrico D, Ohkanda J, Kendrick H, Yokoyama K, Blaskovich M, Bucher C, Buckner F, Van Voorhis W, Chakrabarti D, Croft S, Gelb M, Sebti S, HamiltonAD. In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability. Bioorg Med Chem. 2004;12(24):6517-6526. Pubmedid: 15556768.   Pubmed ID: 15556768

  68. Dan H, Jiang K, Coppola D, Hamilton A, Nicosia S, Sebti S, Cheng J. Phosphatidylinositol-3-OH kinase/AKT and survivin pathways as critical targets for geranylgeranyltransferase I inhibitor-induced apoptosis. Oncogene. 2004;23(3):706-715. Pubmedid: 14737105.   Pubmed ID: 14737105

  69. Dasgupta P, Sun J, Wang S, Fusaro G, Betts V, Padmanabhan J, Sebti SM, Chellappan SP. Disruption of the Rb--Raf-1 interaction inhibits tumor growth and angiogenesis. Mol Cell Biol. 2004 Nov;24(21):9527-9541. Pubmedid: 15485920.   Pubmed ID: 15485920

  70. Epling-Burnette PK, Bai F, Wei S, Painter JS, Olashaw N, Hamilton A, Sebti S, Djeu JY, Loughran TP. ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL). Oncogene. 2004 Dec;23(57):9220-9229. Pubmedid: 15516985.   Pubmed ID: 15516985

  71. Gasparetto M, Gentry T, Sebti S, O'Bryan E, Nimmanapalli R, Blaskovich M, Bhalla K, Rizzieri D, Haaland P, Dunne J, Smith C. Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening. J Immunol Methods. 2004;292(1-2):59-71. Pubmedid: 15350512.   Pubmed ID: 15350512

  72. Jiang K, Delarue FL, Sebti SM. EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation. Oncogene. 2004 Feb;23(5):1136-1145. Pubmedid: 14647415.   Pubmed ID: 14647415

  73. Jiang K, Sun J, Cheng J, Djeu J, Wei S, Sebti S. Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol. 2004;24(12):5565-5576. Pubmedid: 15169915.   Pubmed ID: 15169915

  74. Mazieres J, Antonia T, Daste G, Muro-Cacho C, Berchery D, Tillement V, Pradines A, Sebti S, Favre G. Loss of RhoB expression in human lung cancer progression. Clin Cancer Res. 2004;10(8):2742-2750. Pubmedid: 15102679.   Pubmed ID: 15102679

  75. Ohkanda J, Buckner F, Lockman J, Yokoyama K, Carrico D, Eastman R, deLuca-Fradley K, Davies W, Croft S, Van Voorhis W, Gelb M, Sebti S, HamiltonAD. Design and synthesis of peptidomimetic protein farnesyltransferase inhibitors as anti-Trypanosoma brucei agents. J Med Chem. 2004;47(2):432-445. Pubmedid: 14711313.   Pubmed ID: 14711313

  76. Paris D, Townsend K, Quadros A, Humphrey J, Sun J, Brem S, Wotoczek-Obadia M, DelleDonne A, Patel N, Obregon D, Crescentini R, Abdullah L, Coppola D, Rojiani A, Crawford F, Sebti S, Mullan M. Inhibition of angiogenesis by Abeta peptides. Angiogenesis. 2004;7(1):75-85. Pubmedid: 15302999.   Pubmed ID: 15302999

  77. Sebti S, Adjei A. Farnesyltransferase inhibitors. Semin Oncol. 2004;31(1):28-39. Pubmedid: 14981578.   Pubmed ID: 14981578

  78. Sun J, Blaskovich MA, Jain RK, Delarue F, Paris D, Brem S, Wotoczek-Obadia M, Lin Q, Coppola D, Choi K, Mullan M, Hamilton AD, Sebti SM. Blocking angiogenesis and tumorigenesis with GFA-116, a synthetic molecule that inhibits binding of vascular endothelial growth factor to its receptor. Cancer Res. 2004 May;64(10):3586-3592. Pubmedid: 15150116.   Pubmed ID: 15150116

  79. Turkson J, Kim J, Zhang S, Yuan J, Huang M, Glenn M, Haura E, Sebti S, Hamilton A, Jove R. Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity. Mol Cancer Ther. 2004;3(3):261-269. Pubmedid: 15026546.   Pubmed ID: 15026546

  80. Turkson J, Zhang S, Palmer J, Kay H, Stanko J, Mora L, Sebti S, Yu H, Jove R. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther. 2004;3(12):1533-1542. Pubmedid: 15634646.   Pubmed ID: 15634646

  81. Yang L, Dan H, Sun M, Liu Q, Sun XM, Feldman RI, Hamilton AD, Polokoff M, Nicosia SV, Herlyn M, Sebti SM, Cheng JQ. Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res. 2004 Jul;64(13):4394-4399. Pubmedid: 15231645.   Pubmed ID: 15231645

  82. Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R, Sebti SM. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res. 2003 Mar;63(6):1270-1279. Pubmedid: 12649187.   Pubmed ID: 12649187

  83. Bolick S, Landowski T, Boulware D, Oshiro M, Ohkanda J, Hamilton A, Sebti S, Dalton W. The farnesyl transferase inhibitor, FTI-277, inhibits growth and induces apoptosis in drug-resistant myeloma tumor cells. Leukemia. 2003;17(2):451-457. Pubmedid: 12592346.   Pubmed ID: 12592346

  84. Bordier BB, Ohkanda J, Liu P, Lee SY, Salazar FH, Marion PL, Ohashi K, Meuse L, Kay MA, Casey JL, Sebti SM, Hamilton AD, Glenn JS. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. J Clin Invest. 2003;112(3):407-414. Pubmedid: 12897208.   Pubmed ID: 12897208

  85. Buckner F, Yokoyama K, Lockman J, Aikenhead K, Ohkanda J, Sadilek M, Sebti S, Van Voorhis W, Hamilton A, Gelb MH. A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents. Proc Natl Acad Sci U S A. 2003 Dec;100(25):15149-15153. Pubmedid: 14657358. Pmcid: PMC299928.   Pubmed ID: 14657358

  86. Doisneau-Sixou S, Cestac P, Chouini S, Carroll J, Hamilton A, Sebti S, Poirot M, Balaguer P, Faye J, Sutherland R, Favre G. Contrasting effects of prenyltransferase inhibitors on estrogen-dependent cell cycle progression and estrogen receptor-mediated transcriptional activity in MCF-7 cells. Endocrinology. 2003;144(3):989-998. Pubmedid: 12586776.   Pubmed ID: 12586776

  87. Forsberg M, Blomgran R, Lerm M, Sarndahl E, Sebti SM, Hamilton A, StendahlO, Zheng L. Differential effects of invasion by and phagocytosis of Salmonella typhimuriumon apoptosis in human macrophages: potential role of Rho-GTPases and Akt. J Leukoc Biol. 2003 Oct;74(4):620-629. Pubmedid: 12960245.   Pubmed ID: 12960245

  88. Mazzocca A, Giusti S, Hamilton AD, Sebti SM, Pantaleo P, Carloni V. Growth inhibition by the farnesyltransferase inhibitor FTI-277 involves Bcl-2 expression and defective association with Raf-1 in liver cancer cell lines. Mol Pharmacol. 2003 Jan;63(1):159-166. Pubmedid: 12488548.   Pubmed ID: 12488548

  89. Ohkanda J, Blaskovich M, Sebti S, Hamilton A. The development of protein farnesyltransferase inhibitors as signaling-based anticancer agents. Prog Cell Cycle Res. 2003;5:211-217. Pubmedid: 14593715.   Pubmed ID: 14593715

  90. Peng Y, Li C, Chen L, Sebti S, Chen J. Rescue of mutant p53 transcription function by ellipticine. Oncogene. 2003;22(29):4478-4487. Pubmedid: 12881704.   Pubmed ID: 12881704

  91. Santucci R, Mackley P, Sebti S, Alsina M. Farnesyltransferase inhibitors and their role in the treatment of multiple myeloma. Cancer Control. 2003;10(5):384-387. Pubmedid: 14581893.   Pubmed ID: 14581893

  92. Sebti S, Der C. Opinion: Searching for the elusive targets of farnesyltransferase inhibitors. Nat Rev Cancer. 2003;3(12):945-951. Pubmedid: 14737124.   Pubmed ID: 14737124

  93. Sebti S. Blocked pathways: FTIs shut down oncogene signals. Oncologist. 2003;8(Suppl):30-38. Pubmedid: 14671226.   Pubmed ID: 14671226

  94. Sun J, Ohkanda J, Coppola D, Yin H, Kothare M, Busciglio B, Hamilton A, Sebti S. Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice. Cancer Res. 2003;63(24):8922-8929. Pubmedid: 14695209.   Pubmed ID: 14695209

  95. Zhang Z, Wang Y, Lantry L, Kastens E, Liu G, Hamilton A, Sebti S, LubetRA, You M. Farnesyltransferase inhibitors are potent lung cancer chemopreventive agents inA/J mice with a dominant-negative p53 and/or heterozygous deletion of Ink4a/Arf. Oncogene. 2003;22:6257-6265. Pubmedid: 13679864.   Pubmed ID: 13679864

  96. Zhu K, Hamilton A, Sebti S. Farnesyltransferase inhibitors as anticancer agents: current status. Curr Opin Investig Drugs. 2003;4(12):1428-1435. Pubmedid: 14763128.   Pubmed ID: 14763128

  97. Adnane J, Muro-Cacho C, Mathews L, Sebti S, Munoz-Antonia T. Suppression of RhoB expression in invasive carcinoma from head and neck cancer patients. Clin Cancer Res. 2002;8(7):2225-2232. Pubmedid: 12114424.   Pubmed ID: 12114424

  98. Adnane J, Seijo E, Chen Z, Bizouarn F, Leal M, Sebti S, Munoz-Antonia T. RhoB, not RhoA, represses the transcription of the transforming growth factor beta type II receptor by a mechanism involving activator protein 1. J Biol Chem. 2002;277(10):8500-8507. Pubmedid: 11741970.   Pubmed ID: 11741970

  99. Arteaga CL, Khuri F, Krystal G, Sebti S. Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer. Semin Oncol. 2002 Feb;29(1 Supp 4):15-26. Pubmedid: 11894010.   Pubmed ID: 11894010

  100. Burdelya L, Catlett-Falcone R, Levitzki A, Cheng F, Mora L, Sotomayor E, Coppola D, Sun J, Sebti S, Dalton W, Jove R, Yu H. Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone. Mol Cancer Ther. 2002;1(11):893-899. Pubmedid: 12481410.   Pubmed ID: 12481410

  101. Crespo N, Delarue F, Ohkanda J, Carrico D, Hamilton A, Sebti S. The farensyltransferase inhibitor, FTI-2153, inhibits bipolar spindle formation during mitosis independently of transformation and Ras and p53 mutation status. Cell Death Differ. 2002;9(7):702-709. Pubmedid: 12058275.   Pubmed ID: 12058275

  102. Jackson R, Adnane J, Coppola D, Cantor A, Sebti S, Pledger W. Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models. Oncogene. 2002;21(55):8486-8497. Pubmedid: 12466968.   Pubmed ID: 12466968

  103. Li X, Liu L, Tupper J, Bannerman D, Winn R, Sebti S, Hamilton A, Harlan J. Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem. 2002;277(18):15309-15316. Pubmedid: 11839765.   Pubmed ID: 11839765

  104. Ohkanda J, Knowles D, Blaskovich M, Sebti S, Hamilton A. Inhibitors of protein farnesyltransferase as novel anticancer agents. Curr Top Med Chem. 2002;2(3):303-323. Pubmedid: 11944822.   Pubmed ID: 11944822

  105. Ohkanda J, Lockman J, Kothare M, Qian Y, Blaskovich M, Sebti S, Hamilton AD. Design and synthesis of potent nonpeptidic farnesyltransferase inhibitors based on a terphenyl scaffold. J Med Chem. 2002;45(1):177-188. Pubmedid: 11754590.   Pubmed ID: 11754590

  106. Walters C, Pryce G, Hankey D, Sebti S, Hamilton A, Baker D, Greenwood J, Adamson P. Inhibition of Rho GTPases with protein prenyltransferase inhibitors prevents leukocyte recruitment to the central nervous system and attenuates clinical signs of disease in an animal model of multiple sclerosis. J Immunol. 2002;168(8):4087-4094. Pubmedid: 11937568.   Pubmed ID: 11937568

  107. Crespo N, Ohkanda J, Yen T, Hamilton A, Sebti S. The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells. J Biol Chem. 2001;276(19):16161-16167. Pubmedid: 11154688.   Pubmed ID: 11154688

  108. Delarue F, Taylor B, Sebti S. Ras and RhoA suppress whereas RhoB enhances cytokine-induced transcription of nitric oxide synthase-2 in human normal liver AKN-1 cells and lung cancer A-549 cells. Oncogene. 2001;20(45):6531-6537. Pubmedid: 11641777.   Pubmed ID: 11641777

  109. Finder J, Petrus J, Hamilton A, Villavicencio R, Pitt B, Sebti S. Signal transduction pathways of IL-1beta-mediated iNOS in pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2001;281(4):L816-L823. Pubmedid: 11557585.   Pubmed ID: 11557585

  110. Kucich U, Rosenbloom J, Herrick D, Abrams W, Hamilton A, Sebti S, Rosenbloom J. Signaling events required for transforming growth factor-beta stimulation of connective tissue growth factor expression by cultured human lung fibroblasts. Arch Biochem Biophys. 2001;395(1):103-112. Pubmedid: 11673871.   Pubmed ID: 11673871

  111. Ohkanda J, Lockman J, Yokoyama K, Gelb M, Croft S, Kendrick H, Harrell M, Feagin J, Blaskovich M, Sebti S, Hamilton A. Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity. Bioorg Med Chem Lett. 2001;11(6):761-764. Pubmedid: 11277514.   Pubmed ID: 11277514

  112. Teng S, Sun J, Irby R, Hamilton A, Sebti S, Yeatman T. V-Src transformation is mediated through farnesylated protein. J Surg Res. 2001;99(2):343-346. Pubmedid: 11469908.   Pubmed ID: 11469908

  113. Turkson J, Ryan D, Kim J, Zhang Y, Chen Z, Haura E, Laudano A, Sebti S, Hamilton A, Jove R. Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation. J Biol Chem. 2001;276(48):45443-45455. Pubmedid: 11579100.   Pubmed ID: 11579100

  114. Adnane J, Bizouarn F, Chen Z, Ohkanda J, Hamilton A, Munoz-Antonia T, Sebti S. Inhibition of farnesyltransferase increases TGFbeta type II receptor expression and enhances the responsiveness of human cancer cells to TGFbeta. Oncogene. 2000;19(48):5525-5533. Pubmedid: 11114730.   Pubmed ID: 11114730

  115. Adnane J, Jackson R, Nicosia S, Cantor A, Pledger W, Sebti S. Loss of p21WAF1/CIP1 accelerates Ras oncogenesis in a transgenic/knockout mammary cancer model. Oncogene. 2000;19(47):5338-5347. Pubmedid: 11103935.   Pubmed ID: 11103935

  116. Allal C, Favre G, Couderc B, Sandrine S, Sizou S, Hamilton A, Sebti S, LajoieMazenc I, Pradines A. RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription. J Biol Chem. 2000;275(40):31001-31008. Pubmedid: 11027361.   Pubmed ID: 11027361

  117. Blaskovich M, Lin Q, Delarue F, Sun J, Park H, Coppola D, Hamilton A, Sebti S. Design of GFB-111, a platelet-derived growth factor binding molecule with antiangiogenic and anticancer activity against human tumors in mice. Nat Biotechnol. 2000;18(10):1065-1070. Pubmedid: 11017044.   Pubmed ID: 11017044

  118. Boota A, Johnson B, Lee K, Blaskovich M, Liu S, Kagan V, Hamilton A, Pitt B, Sebti S, Davies P. Prenyltransferase inhibitors block superoxide production by pulmonary vascular smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2000;278(2):L329-L334. Pubmedid: 10666117.   Pubmed ID: 10666117

  119. Carloni V, Pinzani M, Giusti S, Romanelli R, Parola M, Belloma G, Failli P, Hamilton A, Sebti S, Laffi G, Gentilini P. Tyrosine phosphorylation of focal adhesion kinase by PDGF is dependent on ras in human hepatic stellate cells. Hepatology. 2000;31(1):131-140. Pubmedid: 10613738.   Pubmed ID: 10613738

  120. Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti S. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J Biol Chem. 2000;275(4):17974-17978. Pubmedid: 10770919.   Pubmed ID: 10770919

  121. Cohen E, Muschel R, McKenna W, Evans S, Cerniglia G, Mick R, Kusewitt D, Sebti S, Hamilton A, Oliff A, Kohl N, Gibbs J, Bernhard E. Farnesyltransferase inhibitors potentiate the antitumor effect of radiation on a human tumor xenograft expressing activated HRAS. Radiat Res. 2000;152(2):125-132. Pubmedid: 10931682.   Pubmed ID: 10931682

  122. Cohen-Jonathan E, Muschel R, Gillies McKenna W, Evans S, Cerniglia G, MickR, Kusewitt D, Sebti S, Hamilton A, Oliff A, Kohl N, Gibbs J, Bernhard E. Farnesyltransferase inhibitors potentiate the antitumor effect of radiation on a human tumor xenograft expressing activated HRAS. Radiat Res. 2000;154(2):125-132. Pubmedid: 10931682.   Pubmed ID: 10931682

  123. Coxon F, Helfrich M, Van't Hof R, Ralston S, Hamilton A, Sebti S, Ralston S, Rogers M. Protein geranylgeranylation is required for osteoclast formation, function, and survival: inhibition by bisphosphonates and GGTI-298. J Bone Miner Res. 2000;15(8):1467-1476. Pubmedid: 10934645.   Pubmed ID: 10934645

  124. Dey A, She H, Kim L, Buroch A, Guris D, Carlberg K, Sebti S, Woodley D, Imamoto A, Li W. Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression. Mol Biol Cell. 2000;11(11):3835-3848. Pubmedid: 11071910.   Pubmed ID: 11071910

  125. Jiang K, Coppola D, Crespo N, Hamilton A, Nicosia S, Sebti S, Cheng J. The phosphoinositide 3-OH kinase/AKT2 pathway as a critical target for farnesyltransferase inhibitor-induced apoptosis. Mol Cell Biol. 2000;20(1):139-148. Pubmedid: 10594016.   Pubmed ID: 10594016

  126. Kothare M, Ohkanda J, Lockman J, Qian Y, Blaskovich M, Sebti S, Hamilton A. Development of a tripeptide mimetic strategy for the inhibition of protein farnesyltransferase. Tetrahedron Lett. 2000;56:9833-9841. Pubmedid: noPMID.  

  127. Kucich U, Rosenberg J, Shen G, Abrams W, Hamilton A, Sebti S, Rosenberg J. TGF-beta1 stimulation of fibronectin transcription in cultured human lung fibroblasts requires active geranylgeranyl transferase I, phosphatidylcholine-specific phospholipase C, protein kinase C-delta, and p38, but not erk1/erk2. Arch Biochem Biophys. 2000;374(2):313-324. Pubmedid: 10666313.   Pubmed ID: 10666313

  128. Lantry L, Zhang Z, Yao R, Crist K, Wang Y, Ohkanda J, Hamilton A, Sebti S, Lubet R, You M. Effect of farnesyltransferase inhibitor FTI-276 on established lung adenomas from A/J mice induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Carcinogenesis. 2000;21(1):113-116. Pubmedid: 10607742.   Pubmed ID: 10607742

  129. Qian Y, Marugan J, Fossum R, Vogt A, Sebti S, Hamilton A. Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors. Biorg Med Chem Lett. 2000;7(12):3011-3024. Pubmedid: 10658608.   Pubmed ID: 10658608

  130. Rosenbloom J, Saitta B, Gaidarova S, Sandorfi N, Rosenbloom JC, Abrams W, Hamilton A, Sebti S, Kucich U, Jimenez S. Inhibition of type I collagen gene expression in normal and systemic sclerosis fibroblasts by a specific inhibitor of geranylgeranyl transferase I. Arthritis Rheum. 2000;43(7):1624-1632. Pubmedid: 10902768.   Pubmed ID: 10902768

  131. Sebti S, Hamilton A. Design of growth factor antagonists with antiangiogenic and antitumor properties. Oncogene. 2000;19(56):6566-6573. Pubmedid: 11426641.   Pubmed ID: 11426641

  132. Sebti S, Hamilton A. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lesssons from mechanisms and bench-to-bedside translational studies. Oncogene. 2000;19(56):6584-6593. Pubmedid: 11426643.   Pubmed ID: 11426643

  133. Sebti S, Hamilton A. Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: important mechanistic and bench to bedside issues. Expert Opin Investig Drugs. 2000;9(12):2767-2782. Pubmedid: 11093352.   Pubmed ID: 11093352

  134. Sebti S, Hamilton A. Inhibition of Rho GTPases using protein geranylgeranyltransferase I inhibitors. Methods Enzymol. 2000;325:381-388. Pubmedid: 11036620.   Pubmed ID: 11036620

  135. Sun J, Nam S, Lee C, Li B, Coppola D, Hamilton A, Dou Q, Sebti S. CEP1612, a dipeptidyl proteasome inhibitor, induces p21WAF1 and p27KIP1 expression and apoptosis and inhibits the growth of the human lung adenocarcinoma A-549 in nude mice. Cancer Res. 2000;61(4):1280-1284. Pubmedid: 11245420.   Pubmed ID: 11245420

  136. Wei S, Gilvary D, Corliss B, Sebti S, Sun J, Straus D, Leibson P, Trapain J, Hamilton A, Weber M, Djeu J. Direct tumor lysis by NK cells uses a Ras-independent mitogen-activated protein kinase signal pathway. J Immunol. 2000;165(7):3811-3819. Pubmedid: 11034387.   Pubmed ID: 11034387

  137. Zhang H, Wei S, Sun J, Coppola D, Zhong B, Wu G, Goodwin B, Sebti S, Djeu JY, Blanck G. Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice. Cell Growth Differ. 2000;11(12):635-639. Pubmedid: 11149598.   Pubmed ID: 11149598

  138. Bowman T, Yu H, Sebti S, Dalton W, Jove R. Signal transducers and activators of transcription: novel targets for anticancer therapeutics. Cancer Control. 1999;6(5):427-435. Pubmedid: 10758575.   Pubmed ID: 10758575

  139. Cohen E, Toulas C, Ader I, Monteil A, Allal C, Bonnet J, Hamilton A, Sebti S, Daly-Schveitzer N, Favre G. The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS. Radiat Res. 1999;152(4):404-411. Pubmedid: 10477917.   Pubmed ID: 10477917

  140. Liu L, Moesner P, Kovach N, Hamilton A, Sebti S, Harlan J. Integrin-dependent leukocyte adhesion involves geranylgeranylated protein(s). J Biol Chem. 1999;274(47):33334-33340. Pubmedid: 10559211.   Pubmed ID: 10559211

  141. Mazet J, Padieu M, Osman H, Maume G, Mailliet P, Dereu N, Hamilton A, Lavelle F, Sebti S, Maume B. Combination of the novel farnesyltransferase inhibitor RPR130401 and the geranylgeranyltransferase-1 inhibitor GGTI-298 disrupts MAP kinase activation and G(1)-S transition in Ki-Ras-overexpressing transformed adrenocortical cells. Febs Lett. 1999;460(2):235-240. Pubmedid: 10544242.   Pubmed ID: 10544242

  142. O'Conner S, Barr K, Wang L, Sorensen B, Tasker A, Sham H, Ng S, Cohen J, Devine E, Cherian S, Saeed B, Zhang H, Lee J, Warner R, Tahir S, Kovar P, Ewing P, Alder J, Mitten M, Leal J, Marsh K, Bauch J, Hoffman D, Sebti S, Rosenberg S. Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy. J Med Chem. 1999;42(18):3701-3710. Pubmedid: 10479301.   Pubmed ID: 10479301

  143. Pollack I, Bredel M, Erff M, Hamilton A, Sebti S. Inhibition of Ras and related guanosine triphosphate-dependent proteins as a therapeutic strategy for blocking malignant glioma growth: II--preclinical studies in a nude mouse model. Neurosurgery. 1999;45(5):1208-1214. Pubmedid: 10549939.   Pubmed ID: 10549939

  144. Sun J, Blaskovich M, Knowles D, Qian Y, Ohkanda J, Bailey R, Hamilton A, Sebti S. Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase I: combination therapy with the cytotoxic agents cisplatin, taxol and gemcitabine. Cancer Res. 1999;59(19):4919-4926. Pubmedid: 10519405.   Pubmed ID: 10519405

  145. Sun Z, Qian Y, Chen Z, Marfurt J, Hamilton A, Sebti S. The geranylgeranyltransferase I inhibitor GGTI-298 induces hypophosphorylation of Rb and partner switching of cyclin-dependent kinase inhibitors: a potential mechanism for GGTI-298 antitumor activity. J Biol Chem. 1999;274:6930-6934. Pubmedid: 10066746.   Pubmed ID: 10066746

  146. Turkson J, Bowman T, Adnane J, Zhang Y, Djeu J, Sekharam M, Frank D, Holzman L, Wu J, Sebti S, Jove R. Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the src oncoprotein. Mol Cell Biol. 1999;19(11):7519-7528. Pubmedid: 10523640.   Pubmed ID: 10523640

  147. Vasudevan A, Qian Y, Vogt A, Blaskovich M, Sebti S, Hamilton A. Potent, highly selective and non-thiol inhibitors of geranylgeranyltransferase I. J Med Chem. 1999;42(8):1333-1340. Pubmedid: 10212118.   Pubmed ID: 10212118

  148. Adnane J, Bizouarn F, Qian Y, Hamilton A, Sebti S. p21(WAF1/CIP1) is upregulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor beta- and Sp1-responsive element: involvement of the small GTPase rhoA. Mol Cell Biol. 1998;18(12):6962-6970. Pubmedid: 09819384.   Pubmed ID: 09819384

  149. Bernhard E, McKenna W, Hamilton A, Sebti S, Qian Y, Muschel R. Inhibiting Ras prenylation increases the radiosensitivity of human tumor cell lines with activating mutations of ras oncogenes. Cancer Res. 1998;58(8):1754-1761. Pubmedid: 09563495.   Pubmed ID: 09563495

  150. Bredel M, Pollack I, Freund J, Hamilton A, Sebti S. Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking malignant glioma growth. Neurosurgery. 1998;43(1):124-132. Pubmedid: 09657198.   Pubmed ID: 09657198

  151. Hamilton A, Sebti S. New approaches to anticancer drug design based on the inhibition of farnesyltransferase. Ddt. 1998;3(1):26-33. Pubmedid: noPMID.  

  152. Kucich U, Rosenberg J, Shen G, Abrams W, Blaskovich M, Ohkanda J, Hamilton A, Sebti S, Rosenberg J. Requirement for geranylgeranyl transferase I and acyl transferase in the TGF-beta-stimulated pathway leading to elastin mRNA stabilization. Biochem Biophys Res Commun. 1998;252(1):111-116. Pubmedid: 09813154.   Pubmed ID: 09813154

  153. Qian Y, Vogt A, Vasudevan A, Sebti S, Hamilton A. Selective inhibition of type-I geranylgeranyltransferase in vitro and in whole cells by CAAL peptidomimetics. Biorg Med Chem Lett. 1998;6(3):293-299. Pubmedid: 09568283.   Pubmed ID: 09568283

  154. Sebti S, Hamilton A. New approaches to anti-cancer drug design based on the inhibition of farnesyltransferase. Drug Discovery. 1998;3:26-33. Pubmedid: noPMID.  

  155. Stark W, Blaskovich M, Johnson B, Vasudevan A, Hamilton A, Sebti S, Davies P. Inhibiting geranylgeranylation blocks growth and promotes apoptosis in pulmonary vascular smooth muscle cells. Am J Physiol. 1998;275(1):L55-L63. Pubmedid: 09688935.   Pubmed ID: 09688935

  156. Sun J, Qian Y, Hamilton A, Sebti S. Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts. Oncogene. 1998;16(11):1467-1473. Pubmedid: 09525745.   Pubmed ID: 09525745

  157. Clark G, Kinch M, Rogers-Graham K, Sebti S, Hamilton A, Der C. The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation. J Biol Chem. 1997;272:10609-10615. Pubmedid: 09099708.   Pubmed ID: 09099708

  158. Finder J, Litz J, Blaskovich M, McGuire T, Qian Y, Hamilton A, Davies P, Sebti S. Inhibition of protein geranylgeranylation causes a superinduction of nitric oxide synthase-2 by interleukin-1(beta) in vascular smooth muscle cells. J Biol Chem. 1997;272:13484-13488. Pubmedid: 09153192.   Pubmed ID: 09153192

  159. Lerner E, Hamilton A, Sebti S. Inhibition of Ras prenylation: a signaling target for novel anticancer drug design. Anticancer Drug Design. 1997;12:229-238. Pubmedid: 09199657.   Pubmed ID: 09199657

  160. Lerner E, Zhang T, Knowles D, Qian Y, Hamilton A, Sebti S. Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines. Oncogene. 1997;15(11):1283-1288. Pubmedid: 09315095.   Pubmed ID: 09315095

  161. Miquel K, Pradines A, Sun J, Hamilton A, Sebti S, Favre G, Qian Y. GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res. 1997;57(10):1846-1850. Pubmedid: 09157972.   Pubmed ID: 09157972

  162. Qian Y, Sebti S, Hamilton A. Farnesyltransferase as as target for anti-cancer drug design. Biopolymers. 1997;43:25-41. Pubmedid: 09174410.   Pubmed ID: 09174410

  163. Qian Y, Sebti S, Hamilton A. Peptidomimetic inhibitors of farnesyltransferase: an approach to new antitumor agents. Adv Amino Acid Mem And Pep. 1997;1:165-192. Pubmedid: noPMID.  

  164. Sebti S, Hamilton A. Anticancer activity of farnesyltransferase and geranylgeranyltransferase I inhibitors: prospects for drug development. Expert Opinion On Inv Drugs. 1997;6:1711-1714. Pubmedid: 15989575.   Pubmed ID: 15989575

  165. Sebti S, Hamilton A. Inhibition of Ras prenylation: a novel approach to cancer chemotherapy. Pharmacol Ther. 1997;74(1):103-114. Pubmedid: 09336018.   Pubmed ID: 09336018

  166. Sebti S, Hamilton A. Inhibitors of prenyltransferases. Curr Opin Oncol. 1997;9:557-561. Pubmedid: 09370077.   Pubmed ID: 09370077

  167. Sebti S, McGuire T. Geranylgeraniol potentiates lovastatin inhibition of oncogenic H-Ras processing and signaling while preventing cytotoxicity. Oncogene. 1997;14:305-312. Pubmedid: 09018116.   Pubmed ID: 09018116

  168. Vogt A, Sun J, Qian Y, Hamilton A, Sebti S. The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21 (WAF1/CIP1/SDI1) in a p53-independent manner. J Biol Chem. 1997;272(43):27224-27229. Pubmedid: 09341167.   Pubmed ID: 09341167

  169. Bernhard E, Kao G, Cox A, Sebti S, Hamilton A, Muschel R, McKenna W. The farnesyltransferase inhibitor FTI-277 radiosensitizes Ras (H)-transformed rat embryo fibroblasts. Cancer Res. 1996;56:1727-1730. Pubmedid: 08620483.   Pubmed ID: 08620483

  170. Der C, Cox A, Sebti S, Hamilton A. Farnesyltransferase inhibitors: anti-Ras drugs for cancer treatment?. Anticancer Drugs. 1996;7:165-172.  

  171. McGuire T, Qian Y, Hamilton A, Sebti S. Platelet derived growth factor receptor tyrosine phosphorylation reqiures protein geranylgeranylation and not farnesylation. J Biol Chem. 1996;271:27402-27407. Pubmedid: 08910319.   Pubmed ID: 08910319

  172. Pei Z, Sebti S. Cys (102) and His (398) are required for bleomycin-inactivating activity but not for hexamer formation of yeast bleomycin hydrolase. Biochemistry. 1996;35:10751-10756. Pubmedid: 08718865.   Pubmed ID: 08718865

  173. Qian Y, Vogt A, Sebti S, Hamilton A. Design and synthesis of non-peptide Ras CAAX mimetics as potent farnesyltransferase inhibitors. J Med Chem. 1996;39:217-233. Pubmedid: 08568811.   Pubmed ID: 08568811

  174. Sebti S, Hamilton A. Rational design of Ras prenyltransferase inhibitors as potential anticancer drugs. Biochem Soc Trans. 1996;24:692-699. Pubmedid: 08878828.   Pubmed ID: 08878828

  175. Vogt A, Qian Y, McGuire T, Hamilton A, Sebti S. Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. Oncogene. 1996;13:1991-1999. Pubmedid: 08934546.   Pubmed ID: 08934546

  176. Xu X, McGuire T, Blaskovitch M, Sebti S, Romero G. Effects of lovastatin on the stimulation of mitogen-activated protein (MAP) kinase by insulin in HIRcB fibroblasts. Arch Biochem Biophys. 1996;326:233-237. Pubmedid: 08611028.   Pubmed ID: 08611028

  177. Kauffman R, Qian Y, Vogt A, Sebti S, Hamilton A, Carthew R. Activated drosophila Ras 1 is selectively suppressed by isoprenylthransferase inhibitors. Proc Natl Acad Sci U S A. 1995;92:10919-10923. Pubmedid: 07479910.   Pubmed ID: 07479910

  178. Lerner E, Qian Y, Blaskovitch S, FOssum R, Vogt A, Cox A, Der C, Hamilton A, Sebti S. Ras CAAX peptidomimetic FTI 277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras/Raf complexes. J Biol Chem. 1995;270:26802-26806. Pubmedid: 07592920.   Pubmed ID: 07592920

  179. Lerner E, Qian Y, Hamilton A, Sebti S. Disruption of oncogenic K-Ras 4B processing and signaling by a potent Geranylgcranyltransferase I inhibitor. J Biol Chem. 1995;270:26770-26773. Pubmedid: 07592913.   Pubmed ID: 07592913

  180. McGuire T, Qian Y, Blaskovich M, Fossum R, Sun J, Marlowe T, Corey S, Wathen S, Vogt A, Hamilton A, Sebti S. CAAX peptidomimetic FTI-244 decreases platelet-dervied growth factor receptor tyrosine phosphorylation levels and inhibits stimulation of phosphatidylinositol 3-kinase but not mitogen-activated protein kinase. Biochem Biophys Res Commun. 1995;214:295-303. Pubmedid: 07669049.   Pubmed ID: 07669049

  181. Pei Z, Calmels T, Creutz C, Sebti S. Yeast cysteine proteinase YCP1 gene induces bleomycin resistance in mammalian cells. Mol Pharmacol. 1995;48:676-681. Pubmedid: 07476893.   Pubmed ID: 07476893

  182. Sun J, Qian Y, Hamilton A, Sebti S. Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion. Cancer Res. 1995;55:4243-4247. Pubmedid: 07671229.   Pubmed ID: 07671229

  183. Vogt A, Qian Y, Blaskovich M, Fossum R, Hamilton A, Sebti S. A non-peptide mimetic of Ras CAAX: selective inhibition of farnesyltransferase and Ras processing. J Biol Chem. 1995;270:660-664. Pubmedid: 07822292.   Pubmed ID: 07822292

  184. Vogt A, Sun J, Qian Y, Hamilton A, Sebti S. Burkitt lymphoma Daudi cells contain two district farnesyltransferases with different divalent cation requirements. Biochemistry. 1995;34:12398-12403. Pubmedid: 07547984.   Pubmed ID: 07547984

  185. McGuire T, Xu X, Corey S, Romero G, Sebti S. Lovastatin disrupts early events in insulin signaling: A potential mechanism of lovastatin's anti-mitogenic activity. Biochem Biophys Res Commun. 1994;204:399-406.  

  186. Qian Y, Blaskovich M, Saleem M, Wathen S, Hamilton A, Sebti S. Design and structural requirements of potent peptidomimetic inhibitors of p21ras Farnesyl transferase. J Biol Chem. 1994;269:12410-12413.  

  187. McGuire T, Corey S, Sebti S. Lovastatin inhibits PDGF stimulation of phosphatidyl inositol 3-kinase activity as well as the association of p85 subunit to tyrosine-phosphorylated PDGF receptor. J Biol Chem. 1993;268:22227-22230.  

  188. Nigam M, Seong C, Qian Y, Hamilton A, Sebti S. Potent inhibition of human tumor p21 ras farnesyl transferase by A(1)A(2)-lacking CA(1)A(2)X peptidominetics. J Biol Chem. 1993;268:20695-20698.  

  189. Jani J, Mistry J, Morris G, Lazo J, Sebti S. In vivo circumvention of human colon carcinoma resistance to bleomycin. Cancer Res. 1992;52:2931-2937.  

  190. Mistry J, Jani J, Morris G, Mujumdar R, Reynolds J, Sebti S, Lazo J. Synthesis and evaluation of a novel fluorescence-labelled derivative of talismycin S (10b) as a probe for identifying bleomycin-resistant cells. Cancer Res. 1992;52:709-718.  

  191. Morris G, Mistry J, Jani J, Mignano J, Sebti S, Lazo J. Neutralization of bleomycin hydrolase by an epitope-specific antibody. Mol Pharmacol. 1992;42:57-62.  

  192. Lazo J, Hoyt D, Sebti S, Pitt B. The use of bleomycin in model systems to study the pathogenesis of interstitial pulmonary fibrosis. In: Gram T, ed. International encyclopedia of pharmacology and therapeutics. Oxford. Pregmon Press, Ltd; 1992;271-287.  

  193. Lazo J, Sebti S. Bleomycin. In: Pindeo H, Longo D, Chabner B, et al, eds. Cancer chemotherapy and Biological Response Modifiers. 17 ed. Amsterdam. Elsevier Science Publishers B.V. (Biochemical Division); 1997;40-45.  

  194. Sebti S, Lazo J. Bleomycin hydrolase and tumor resistance to bleomycin. In: Sartorelli A, Powis P, eds. International Encyclopedia of Pharmacology and Therapeutics. Oxford. Pergamon Press Ltd; 1994;387-396.  

Said M. Sebti, PhD

Below is a list of active grants where the faculty member is the Principal Investigator. Grants are sorted by sponsor and then sorted by start date, with the more recent grant shown first.

STAT1 Activation and Hpp 1 Tumor Supression

5 R01 CA131398-02
Sponsor: Nat Institutes of Health / NCI
Project Dates: July 1, 2009 to May 31, 2014
Annual Direct Cost: $207,500
Annual Total Cost: $346,525
Project Total: $1,732,625

Targeting STAT3 as a Novel Approach to Cancer Therapy

5 R01 CA140681-02
Sponsor: Nat Institutes of Health / NCI
Project Dates: July 1, 2009 to May 31, 2014
Annual Direct Cost: $213,077
Annual Total Cost: $355,838
Project Total: $1,824,967

Validating and targeting Lysophosphatidic Acid Acyltransferase-Beta in Cancer

5 R01 CA131400-02
Sponsor: Nat Institutes of Health / NCI
Project Dates: July 1, 2009 to May 31, 2014
Annual Direct Cost: $207,500
Annual Total Cost: $346,525
Project Total: $1,732,625

Targeting Signal transduction Pathways for Cancer Drug Discovery

3 P01 CA118210-04S1
Sponsor: Nat Institutes of Health / NCI
Project Dates: February 5, 2007 to January 31, 2011
Annual Direct Cost: $1,345,772
Annual Total Cost: $2,081,048
Project Total: $8,955,251

Targeted Intervention of Breast Oncogenic Pathways

2 R01 CA098473-06A2
Sponsor: Nat Institutes of Health / NCI
Project Dates: June 1, 2003 to March 31, 2015
Annual Direct Cost: $195,569
Annual Total Cost: $319,306
Project Total: $1,511,848

Molecular Signatures for Colon Cancer

08BR-02
Sponsor: State of Florida / Dept of Health
Project Dates: July 1, 2008 to June 30, 2011
Annual Direct Cost: $270,455
Annual Total Cost: $297,500
Project Total: $970,000

Researcher  Contact Form

© Copyright 1996 - 2010 H. Lee Moffitt Cancer Center & Research Institute