Recent Highlights in Covalent Drug Discovery

This talk presents notable case studies in covalent drug discovery that small molecule scientists throughout the industry would find interesting.
00:00 Introduction
00:26 Sponsor Introduction
05:39 Presentation
42:03 Q&A
Presented by: Dennis Hu, CEO & Editor-in-Chief, Drug Hunter
Thank you to Pierre Morieux and Revvity Signals for their support of this webinar.
Presented on September 27, 2023, as a Drug Hunter Flash Talk.
Sign up for future sessions here: lu.ma/w1q906iz

[@Mohakal777]

Thank you drug for sharing your talent of clear understanding in organized way.

[@user-pe3nq2kz3v]

Hi Dennis. I think there may be a misunderstanding. The EPSA means "exposed PSA" not experimental PSA. Please refer to the literature ACS Med. Chem. Lett. 2014, 5, 1167−1172; ACS Med. Chem. Lett. 2022, 13, 6, 964-971. As you mentioned, the intramolecular hydrogen bond of RMC-6291 may sheild the polarity of morpholine and amide, which results in a similar EPSA with compound 5

[@drughunter]

Thank you for your comment! In the original Pfizer paper(s), EPSA (an experimentally determined value from chromatography) was named EPSA in analogy to their previous experimental measure, ELogD (see AMCL 2014). While the "E" wasn't defined in the paper, many started to refer to this as experimental PSA and others exposed PSA, though people are all generally referring to this method.

[@user-xs7nn5ip2p]

could you list the reference for covalent binding to the backbone amine, it's really interesting! thank you!