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The Cheminar

Tuesday, March 21, 2023
11:00 a.m. - 12:00 p.m.

Add to Calendar 2023-03-21 11:00:00 2023-03-21 12:00:00 The Cheminar The Cheminar Herman Nikolayevskiy, Ph.D. Department of Chemistry University of San Francisco Tuesday Mar. 21st Seminar 11 AM – 12 PM Classroom Building CR 170 A Programmable Off-Switch for Chemotherapeutics Molecules that covalently modify DNA represent an important tool in the fight against cancer, but are often characterized by small therapeutic windows due to their high toxicity and poor selectivity. Efforts to decrease the toxicity of DNA-alkylators, such as through antibody-targeting and the selective uncaging (“turning on”) of inert prodrugs, have largely relied on the overproduction of specific proteins or metabolites within cancer cells to elicit their effect. While such efforts have successfully increased the maximum tolerated dose of potent cytotoxins in clinical settings, the exploitable differences between normal cells and cancer cells are often small and insufficient to completely prevent off-target toxicity. Thus, the development of complementary approaches that further increase the therapeutic window of DNA-alkylators remains incredibly valuable. One such orthogonal strategy attempts to take advantage of cancer-specific downregulation to selectively “turn off” activity within normal cells. In this seminar, I will detail our efforts to develop self-immolative small molecules that remain active within cancer cells but respond to stimuli within normal cells to enter an unreactive state via intramolecular cyclization. This novel approach has the potential to further reduce off-target effects and expand the repertoire of clinically tolerated cytotoxic chemotherapies. About the Speaker Herman Nikolayevskiy received his BE in Chemical Engineering from Cooper Union, a primarilyundergraduate institution in the heart of NYC. After a transformative undergraduate research experience, Dr. Nikolayevskiy was inspired to pursue a PhD in Organic Chemistry at Yale University, where he focused on the total synthesis and computational analysis of bioactive natural products under Professor Seth B. Herzon. After leaving New Haven, Dr. Nikolayevskiy did his postdoctoral work at the National Institutes of Health (NIH) with Dr. Daniel H. Appella, where he employed NMR spectroscopy to study the mechanism of action of thioester-based HIV inhibitors. At USF, the Nikolayevskiy group uses its expertise in synthetic chemistry and mechanistic analysis to explore the therapeutic potential of molecular “off-switches” as a strategy for increasing the tolerability of anticancer chemotherapies. Zoom link to join the seminar online. https://pacific.zoom.us/j/93581261718 Zoom Meeting ID: 935 8126 1718 One tap mobile +16699009128,,93581261718# US (San Jose) +12532158782,,93581261718# US (Tacoma) Dial by your location +1 669 900 9128 US (San Jose) +1 253 215 8782 US (Tacoma) +1 346 248 7799 US (Houston) +1 301 715 8592 US (Germantown) +1 312 626 6799 US (Chicago) +1 646 558 8656 US (New York) Meeting ID: 935 8126 1718 Find your local number: https://pacific.zoom.us/u/axmW6NT09 3601 Pacific Ave, Stockton, CA 95211, USA America/Los_Angeles public

The Cheminar

Herman Nikolayevskiy, Ph.D.
Department of Chemistry
University of San Francisco
Tuesday Mar. 21st
Seminar 11 AM – 12 PM
Classroom Building CR 170

A Programmable Off-Switch for Chemotherapeutics Molecules that covalently modify DNA represent an important tool in the fight against cancer, but are often characterized by small therapeutic windows due to their high toxicity and poor selectivity. Efforts to decrease the toxicity of DNA-alkylators, such as through antibody-targeting and the selective uncaging (“turning on”) of inert prodrugs, have largely relied on the overproduction of specific proteins or metabolites within cancer cells to elicit their effect. While such efforts have successfully increased the maximum tolerated dose of potent cytotoxins in clinical settings, the exploitable differences between normal cells and cancer cells are often small and insufficient to completely prevent off-target toxicity. Thus, the development of complementary approaches that further increase the therapeutic window of DNA-alkylators remains incredibly valuable. One such orthogonal strategy attempts to take advantage of cancer-specific downregulation to selectively “turn off” activity within normal cells. In this seminar, I will detail our efforts to develop self-immolative small molecules that remain active within cancer cells but respond to stimuli within normal cells to enter an unreactive state via intramolecular cyclization. This novel approach has the potential to further reduce off-target effects and expand the repertoire of clinically tolerated cytotoxic chemotherapies.

About the Speaker
Herman Nikolayevskiy received his BE in Chemical Engineering from Cooper Union, a primarilyundergraduate institution in the heart of NYC. After a transformative undergraduate research experience, Dr. Nikolayevskiy was inspired to pursue a PhD in Organic Chemistry at Yale University, where he focused on the total synthesis and computational analysis of bioactive natural products under Professor Seth B. Herzon. After leaving New Haven, Dr. Nikolayevskiy did his postdoctoral work at the National Institutes of Health (NIH) with Dr. Daniel H. Appella, where he employed NMR spectroscopy to study the mechanism of action of thioester-based HIV inhibitors. At USF, the Nikolayevskiy group uses its expertise in synthetic chemistry and mechanistic analysis to explore the therapeutic potential of molecular “off-switches” as a strategy for increasing the tolerability of anticancer chemotherapies.

Zoom link to join the seminar online.

https://pacific.zoom.us/j/93581261718

Zoom Meeting ID: 935 8126 1718

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