Andrii Monastyrskyi, PhD
Andrii Monastyrskyi, PhD
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Overview
The Monastyrskyi lab harnesses the power of organic chemistry and chemical biology to develop new tools for studying the function and therapeutic potential of cancer targets.
Associations
- Drug Discovery
- Breast Oncology
- Neuro-Oncology
- Molecular Medicine Program
Education & Training
Graduate:
- University of South Florida, PhD - Organic Chemistry
Fellowship:
- The Scripps Research Institute - Chemistry
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Research Interest
In the Monastyrskyi laboratory, we harness the synergies between synthetic organic chemistry, medicinal chemistry, and chemical biology to innovate small molecules that both elucidate and modulate therapeutically relevant targets in cancer. Our approach is deeply rooted in a hypothesis- driven, mechanistic framework that emphasizes the pivotal role of molecular markers for precise patient selection and the development of pharmacodynamic biomarkers, interconnecting the drug's mechanism of action and its therapeutic efficacy. Our current research is particularly focused on drugging kinases such as CDK11, CDK12/13, and ULK1, chemoproteomics-enabled fragment-based drug discovery, and advancing targeted protein degradation strategies.
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Publications
- Karolak A, Urbaniak K, Monastyrskyi A, Duckett DR, Branciamore S, Stewart PA. Structure-independent machine-learning predictions of the CDK12 interactome. Biophys J. 2024 Sep.123(17):2910-2920. Pubmedid: 38762754. Pmcid: PMC11393676.
- Schmitz M, Kaltheuner IH, Anand K, Düster R, Moecking J, Monastyrskyi A, Duckett DR, Roush WR, Geyer M. The reversible inhibitor SR-4835 binds Cdk12/cyclin K in a noncanonical G-loop conformation. J Biol Chem. 2024 Jan.300(1):105501. Pubmedid: 38016516. Pmcid: PMC10767194.
- Morozova A, Chan SC, Bayle S, Sun L, Grassie D, Iermolaieva A, Kalaga MN, Frydman S, Sansil S, Schönbrunn E, Duckett D, Monastyrskyi A. Development of potent and selective ULK1/2 inhibitors based on 7-azaindole scaffold with favorable in vivo properties. Eur J Med Chem. 2024 Feb.266:116101. Pubmedid: 38232465.
- Liao Y, Remsing Rix LL, Li X, Fang B, Izumi V, Welsh EA, Monastyrskyi A, Haura EB, Koomen JM, Doebele RC, Rix U. Differential network analysis of ROS1 inhibitors reveals lorlatinib polypharmacology through co-targeting PYK2. Cell Chem Biol. 2024 Feb.31(2):284-297.e10. Pubmedid: 37848034. Pmcid: PMC10922442.
- Liao Y, Chin Chan S, Welsh EA, Fang B, Sun L, Schönbrunn E, Koomen JM, Duckett DR, Haura EB, Monastyrskyi A, Rix U. Chemical Proteomics with Novel Fully Functionalized Fragments and Stringent Target Prioritization Identifies the Glutathione-Dependent Isomerase GSTZ1 as a Lung Cancer Target. Acs Chem Biol. 2023 Feb.18(2):251-264. Pubmedid: 36630201.
- Burger KL, Fernandez MR, Meads MB, Sudalagunta PR, Oliveira PS, Renatino Canevarolo R, Alugubelli RR, Tungsevik A, De Avila G, Silva M, Graeter AI, Dai H, Vincelette ND, Prabhu A, Magaletti D, Yang C, Li W, Kulkarni A, Hampton OA, Koomen JM, Roush WR, Monastyrskyi A, Berglund AE, Silva AS, Cleveland JL, Shain KH. CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma. Cancer Res. 2023 Dec.83(23):3901-3919. Pubmedid: 37702657. Pmcid: PMC10690099.
- Nacheva K, Kulkarni SS, Kassu M, Flanigan D, Monastyrskyi A, Iyamu ID, Doi K, Barber M, Namelikonda N, Tipton JD, Parvatkar P, Wang HG, Manetsch R. Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach. J Med Chem. 2023 Apr.66(7):5196-5207. Pubmedid: 37000900.
- Monastyrskyi A, Brockmeyer F, LaCrue AN, Zhao Y, Maher SP, Maignan JR, Padin-Irizarry V, Sakhno YI, Parvatkar PT, Asakawa AH, Huang L, Casandra D, Mashkouri S, Kyle DE, Manetsch R. Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1H)-Quinolones with Single Dose Cures. J Med Chem. 2021 May.64(10):6581-6595. Pubmedid: 33979164. Pmcid: PMC8904075.
- Tadesse S, Duckett DR, Monastyrskyi A. The promise and current status of CDK12/13 inhibition for the treatment of cancer. Future Med Chem. 2021 Jan.13(2):117-141. Pubmedid: 33295810.
- Maharaj K, Powers JJ, Achille A, Mediavilla-Varela M, Gamal W, Burger KL, Fonseca R, Jiang K, Miskin HP, Maryanski D, Monastyrskyi A, Duckett DR, Roush WR, Cleveland JL, Sahakian E, Pinilla-Ibarz J. The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells. Blood Adv. 2020 Jul.4(13):3072-3084. Pubmedid: 32634240. Pmcid: PMC7362385.
- Vena F, Bayle S, Nieto A, Quereda V, Aceti M, Frydman SM, Sansil SS, Grant W, Monastyrskyi A, McDonald P, Roush WR, Teng M, Duckett D. Targeting Casein Kinase 1 Delta Sensitizes Pancreatic and Bladder Cancer Cells to Gemcitabine Treatment by Upregulating Deoxycytidine Kinase. Mol Cancer Ther. 2020 Aug.19(8):1623-1635. Pubmedid: 32430484. Pmcid: PMC7415672.
- Quereda V, Bayle S, Vena F, Frydman SM, Monastyrskyi A, Roush WR, Duckett DR. Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer. Cancer Cell. 2019 Nov.36(5):545-558.e7. Pubmedid: 31668947.
- Monastyrskyi A, Bayle S, Quereda V, Grant W, Cameron M, Duckett D, Roush W. Discovery of 2-arylquinazoline derivatives as a new class of ASK1 inhibitors. Bioorg Med Chem Lett. 2018 Feb.28(3):400-404. Pubmedid: 29277458. Pmcid: PMC5999544.
- Monastyrskyi A, Nilchan N, Quereda V, Noguchi Y, Ruiz C, Grant W, Cameron M, Duckett D, Roush W. Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer. Bioorg Med Chem. 2018 Feb.26(3):590-602. Pubmedid: 29289448. Pmcid: PMC5803353.
- Neelarapu R, Maignan JR, Lichorowic CL, Monastyrskyi A, Mutka TS, LaCrue AN, Blake LD, Casandra D, Mashkouri S, Burrows JN, Willis PA, Kyle DE, Manetsch R. Design and Synthesis of Orally Bioavailable Piperazine Substituted 4(1H)-Quinolones with Potent Antimalarial Activity: Structure-Activity and Structure-Property Relationship Studies. J Med Chem. 2018 Feb.61(4):1450-1473. Pubmedid: 29215279. Pmcid: PMC6610884.
- Monastyrskyi A, Namelikonda NK, Manetsch R. Metal-free arylation of ethyl acetoacetate with hypervalent diaryliodonium salts: an immediate access to diverse 3-aryl-4(1H)-quinolones. J Org Chem. 2015 Mar.80(5):2513-2520. Pubmedid: 25558982. Pmcid: PMC4479256.
- Monastyrskyi A, Kyle DE, Manetsch R. 4(1H)-pyridone and 4(1H)-quinolone derivatives as antimalarials with erythrocytic, exoerythrocytic, and transmission blocking activities. Curr Top Med Chem. 2014 Sep.14(14):1693-1705. Pubmedid: 25116582. Pmcid: PMC4479281.
- Cross RM, Flanigan DL, Monastyrskyi A, LaCrue AN, Sáenz FE, Maignan JR, Mutka TS, White KL, Shackleford DM, Bathurst I, Fronczek FR, Wojtas L, Guida WC, Charman SA, Burrows JN, Kyle DE, Manetsch R. Orally bioavailable 6-chloro-7-methoxy-4(1H)-quinolones efficacious against multiple stages of Plasmodium. J Med Chem. 2014 Nov.57(21):8860-8879. Pubmedid: 25148516. Pmcid: PMC4234439.
- Lacrue AN, Sáenz FE, Cross RM, Udenze KO, Monastyrskyi A, Stein S, Mutka TS, Manetsch R, Kyle DE. 4(1H)-Quinolones with liver stage activity against Plasmodium berghei. Antimicrob Agents Chemother. 2013 Jan.57(1):417-424. Pubmedid: 23129047. Pmcid: PMC3535941.
- Cross RM, Monastyrskyi A, Mutka TS, Burrows JN, Kyle DE, Manetsch R. Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity. J Med Chem. 2010 Oct.53(19):7076-7094. Pubmedid: 20828199.
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Grants
- Title: Development of EWS/FLI targeted therapies for Ewing sarcoma
Sponsor: Florida Biomedical Research Program (FBRP)
PI: Monastyrskyi, A. - Title: Integrated Fragment-Based Phenotypic Screening and Chemoproteomics for Identification of Novel Small Cell Lung Cancer-Specific Targets
Sponsor: Nat Institutes of Health
PI (Contact): Rix, U., PI (MPI): Monastyrskyi, A. - Title: Harnessing CDK12 inhibition for the treatment of HER2+ brain metastatic breast cancers
Sponsor: US Army
PI: Monastyrskyi, A. - Title: Developing CDK12 inhibitors to overcome therapy resistance in HER2+ and KRAS driven breast and lung cancers
Sponsor: Nat Institutes of Health
PI (Contact): Duckett, D., PI (MPI): Monastyrskyi, A., PI (MPI): Haura, E.
- Title: Development of EWS/FLI targeted therapies for Ewing sarcoma