Targeted Protein Degradation in Inflammation and Cancer Therapy

Proteolysis targeting chimera or PROTAC is a novel drug discovery strategy that has brought a paradigm shift and significant opportunity to transform the way medicinal chemistry and drug discovery programs are currently planned and executed. With sub-stoichiometric catalytic mode of action, PROTACs reduce the need for target occupancy as necessitated with traditional small molecule inhibitors. PROTACs hold great promise to target highly mutable kinases and signalling proteins, which promote cancer and drug resistance (e.g., KRAS, BRAF and EGFR).

This webinar will focus on our efforts with PROTACs in the areas of inflammation and cancer. Specifically, we will discuss challenges and opportunities for developing PROTACs in the areas of autoimmune and inflammatory diseases driven by IL-1R/TLR1 signaling and inflammasome activation and in potentially undruggable epigenetic pathways that involve bromodomain proteins, histone acetyltransferases and deacetylases.

Since targeted proteolysis relies on the cellular ubiquitination machinery, expanding the portfolio of E3 ligases will be crucial to broaden the capabilities of targeted protein degradation. This will be particularly impactful from the point of view of tissue specific expression of E3 ligases and those selectively expressed in diseased cells.

This webinar will also address some of the DMPK challenges of PROTACs. Properties of PROTACs fall mostly outside the “Lipinski rule of 5” of small molecule druggability and lead to complex DMPK optimization challenges. There is little IVIV correlation and unique strategies and optimizations are required for orally targeted protein degrader candidates. Panelists will share how the staff at GVK BIO have helped overcome some of these challenges to accelerate the development of PROTACs.

Speakers

Amar Thyagarajan, Ph.D., Global Strategy Head and Head of North America BD (Biology Solutions), GVK Biosciences and Aragen Biosciences

Amar Thyagarajan heads the global strategy and North American business development for the Biology Solutions vertical at GVK BIO and Aragen Biosciences. He is a cell biologist and biochemist by training and holds a PhD in Neuroscience from the State University of New York and completed his post-doctoral fellowship at the Massachusetts Institute of Technology, Cambridge MA. Prior to joining GVK BIO/Aragen, Dr. Thyagarajan held leadership positions at Crown Biosciences and Taconic Biosciences.

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Venkatesh Babu Jayaraman, Principal Scientific Manager, GVK Biosciences

Venkatesh Babu is a Principal Scientific Manager and leads in vitro biology assay development and screening for several PROTAC drug discovery projects at GVK BIO. He has been instrumental in establishing targeted protein degradation assays to support PROTAC research and his team has made significant contributions in screening PROTAC candidates using several assays in medium and high throughput formats. Babu has a Masters degree in Biochemistry from Madurai Kamaraj University and has 2 decades of experience in drug discovery. He has worked on various technology platforms including nanotechnology and high throughput automation.

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