Rapid Hit and Hit-to-Lead Generation in Early Drug Discovery


Thu, 22 Sep 2022, 16:00 CEST (Berlin)

Dr. Debanu Das, XPose Therapeutics, San Francisco, United States of America

Rapid Hit and Hit-to-Lead Generation in Early Drug Discovery

Join us for this webinar! XPose Therapeutics discovers and develops first-in-class target-specific therapeutics, including small molecule inhibitors and targeted protein degraders based on fragment- and structure-based drug discovery. Their approach, “SAR by X-ray Poses Quickly” (“SaXPy”), is founded on a novel technology with two parts: High-throughput X-ray screening of fragment libraries as a primary screen for hit generation, combined with the elucidation of fragment-bound crystal structures. This speeds up fast hit-to-lead development by analog scoping, scaffold hopping, and fragment growth, thus leading to several-fold reduction in early drug discovery efforts.
Debanu will discuss the discovery and complex structure elucidation of novel agents against DNA Damage Response (DDR) targets. These include APE1 and POL η — the first crystal structures of two DDR proteins bound to small molecule ligands. Further, he will present work on FEN1 inhibitors with a KD of 170 nM and discuss how new therapeutics development is facilitated by applying their approach to numerous proteins. Special focus shall be given on novel targets that have rich biology and scientific validation but lack clinical inhibitors (“undruggables”). Debanu will also present how the group’s APE1 inhibitors can be translated for related DDR endonucleases, APE2 and LINE1. Exciting challenges to listen to!

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