953-956 days to go – 31 months
Not surprised APTX doesn’t work. The depression stuff doesn’t work either.
Papers I’ve Read
Discovery and characterization of AZD6738, a potent inhibitor of ataxia telangiectasia mutated and rad3 related (ATR) kinase with application as an anti-cancer agent. Foote et al. J Med Chem 2018.
AstraZeneca’s ATR project has yielded a clinical candidate. 6738 is a suloximine (S=N), replacing the sulfonamide moiety of the hit AZ20. Apparently, this SNOH- moiety hanging off the cyclopropyl did the trick to improve solubility and eliminate CYP3A4 liability (that and one atom on the heterocycle). Anyway, ATR is part of DNA damage repair. You’ve probably heard of it from Vertex, who sold their VX-970 to Merck KgaA (now M-6620 or berzosertib) for a pretty penny. I don’t trust anything from Vertex Cambridge drug discovery (including and especially Derek Lowe). So far I don’t think anyone is bowled over by the data for ATRs–no monotherapy efficacy. There’s a Bayer compound out there, too. It seems like the AZ predecessor compound was around for a while.
6-Benzhydryl-4-amino-quinolin-2-ones as Potent Cannabinoid Type 1 (CB1) Receptor Inverse Agonists and Chemical Modifications for Peripheral Selectivity. Zhang et al. J Med Chem 2018.
J&J researchers produce a peripherally-restricted CB1 agonist to avoid the AE profile of the storied Accomplia. I didn’t know GC1 was the MOST abundant GPCR in the brain–kind of amazing, huh?
Cytokine-Induced Expression of HIV-1 in a Chronically Infected Promonocyte Cell Line. Folks, Fauci, et al. Science 1987.
Human Immunodeficiency Virus-Infected Individuals Contain Provirus in Small Numbers of Perpiheral Mononuclear Cells and at Low Copy Numbers. Simmonds, et al. J Virol 1990.
Still in the way-back-machine for HIV.
Lauren Duca divorced her husband and is gay now. Just 2 and a half years ago she thought it was wise to marry a man. Now all she tweets about is how terrible and useless men are. Play to your audience, I guess. Perhaps she will even become an author, selling her book to a like-minded left-wing gnat (or nut?) at a publishing company that doesn’t realize they’ve been appropriated by ideology. Maybe I should rollup that industry and instill some libertarianism. People should be able to read whatever is appealing, not what some self-anointed anti-business SJW gatekeeper decides.
I wrote more on this and recent revelations that Duca is a body-shamer (the body-shaming posts are awful) and even an ablist/classist as she panned community colleges in a recent Facebook post if you’d like to read it. Evidently even further revelations are forthcoming. Guess her book deal may be off-the-table.