molecules of the year


potent, selective NaV1.7 ion channel inhibitor

completed Ph. I in HV, discontinued in Ph. II

from optimization of known starting point

J. Med. Chem., May 26, 2020

Daiichi Sankyo, Tokyo, JP

1 min read

May’s molecule, the Daiichi Sankyo NaV1.7 inhibitor DS-1971a, is a potent, isoform-selective agent that was intended to treat neuropathic pain. NaV1.7 has been a hot target for pain due to significant human genetic evidence for its role in pain, and non-opioid analgesics are badly needed. The compound has a surprisingly long residence time on NaV1.7, which the authors suggest contributes to better than predicted in vivo activity. It’s a good example of a compound which was successfully advanced to clinical trials despite a PK disconnect between rodents and higher species. There’s also an enormously high bar for safety in pain indications, and in preclinical safety studies, this compound was very well-tolerated in both rodents and cynos (NOAEL = 1000 mg/kg!).…

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