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The Cheminar: Irina Dotsenko, PhD

Tuesday, December 02, 2025
11:00 a.m. - 12:00 p.m.

Add to Calendar 2025-12-02 11:00:00 2025-12-02 12:00:00 The Cheminar: Irina Dotsenko, PhD Tuesday, December 2 | 11:00 a.m. – NoonClassroom Building 170Restoring the function of the guardian of the genome: discovery and development of FMC-220 a highly potent and selective covalent activator of p53 Y220CLoss of function mutations of the TP53 gene are the most common genetic defects across all human cancers. These mutations have long been intractable to drug development. The p53 Y220C mutation is common, occurring in ∼1% of cancers, leading to destabilization, aggregation and loss of p53 protein function. Application of rational and structure-based drug design approaches along with chemo-proteomics platform enabled the discovery of FMC-220, a first-in-class covalent activator of p53 Y220C. FMC-220 works by forming an irreversible covalent bond with the mutant cysteine at amino acid 220 stabilizing the structure and persistently activating the protein. Covalent mechanism of action of FMC-220 leads to unprecedented potency across a panel of Y220C mutant cell lines irrespective of histology. This translates into potent pharmacodynamic activity and tumor regression in Y220C mutant CDX and PDX models in vivo. Importantly, the action of FMC-220 is specific for the Y220C mutant form of the p53 protein, sparing any effect on wild-type p53 function. In addition, FMC-220 is very well tolerated in vivo. These data demonstrate the promise of FMC-220, a first-in-class covalent activator of p53 Y220C, with the potential to deliver improved outcomes for patients with Y220C mutation positive tumors.About the Speaker Over 11 years of progressive experience in medicinal chemistry and small molecule drug discovery serving, with success, as a project team leader, chemistry team leader and key contributor on three programs delivering development candidates:• p53 Y220C activator FMC-220: Inventor, IND submission 2H 2025.• NHE antiport inhibitor RDX011: Co-inventor; progressed into IND-enabling studies.• ITK covalent inhibitor CPI-818: Co-inventor; currently in Phase III clinical trials.EDUCATION Ph.D. in Pharmaceutical and Chemical Sciences, University of the Pacific, Stockton, CA, 2010-2014; Combined B.S. and M.S. in Chemistry, Moscow State University, Russia 2005-2010 3601 Pacific Ave, Stockton, CA 95211, USA America/Los_Angeles public

Tuesday, December 2 | 11:00 a.m. – Noon
Classroom Building 170

Restoring the function of the guardian of the genome: discovery and development of FMC-220 a highly potent and selective covalent activator of p53 Y220C

Loss of function mutations of the TP53 gene are the most common genetic defects across all human cancers. These mutations have long been intractable to drug development. The p53 Y220C mutation is common, occurring in ∼1% of cancers, leading to destabilization, aggregation and loss of p53 protein function. Application of rational and structure-based drug design approaches along with chemo-proteomics platform enabled the discovery of FMC-220, a first-in-class covalent activator of p53 Y220C. FMC-220 works by forming an irreversible covalent bond with the mutant cysteine at amino acid 220 stabilizing the structure and persistently activating the protein. Covalent mechanism of action of FMC-220 leads to unprecedented potency across a panel of Y220C mutant cell lines irrespective of histology. This translates into potent pharmacodynamic activity and tumor regression in Y220C mutant CDX and PDX models in vivo. Importantly, the action of FMC-220 is specific for the Y220C mutant form of the p53 protein, sparing any effect on wild-type p53 function. In addition, FMC-220 is very well tolerated in vivo. These data demonstrate the promise of FMC-220, a first-in-class covalent activator of p53 Y220C, with the potential to deliver improved outcomes for patients with Y220C mutation positive tumors.

About the Speaker

Over 11 years of progressive experience in medicinal chemistry and small molecule drug discovery serving, with success, as a project team leader, chemistry team leader and key contributor on three programs delivering development candidates:
• p53 Y220C activator FMC-220: Inventor, IND submission 2H 2025.
• NHE antiport inhibitor RDX011: Co-inventor; progressed into IND-enabling studies.
• ITK covalent inhibitor CPI-818: Co-inventor; currently in Phase III clinical trials.

EDUCATION

Ph.D. in Pharmaceutical and Chemical Sciences, University of the Pacific, Stockton, CA, 2010-2014; Combined B.S. and M.S. in Chemistry, Moscow State University, Russia 2005-2010