BAY-6672
oral prostaglandin F receptor GCPR antagonist to treat IPF, in vivo efficacy in fibrosis model from ~3M cmpd cell-based HTS and opt. J. Med. Chem., Oct. 22, 2020 issue Bayer AG, Wuppertal, DE
Other molecules you may be interested in
elunonavir
Despite the remarkable emergence of HAART in the 1990s, the fight against HIV infection is by no means finished. At the ACS Fall 2024 meeting in Denver, CO, Gilead Sciences presented the structure and discovery story of elunonavir (GS-1156), a novel HIV protease inhibitor with remarkable metabolic stability and a human half-life exceeding two weeks. Based on BMS’ atazanavir, the compound incorporates structural elements inspired by Gilead’s HCV NS5A inhibitor program which led to ledipasvir, as “stabilizer” motifs to avoid the extensive CYP metabolism seen in current inhibitors.
HC-7366
HiberCell recently disclosed the discovery of HC-7366, a potential first-in-class, intentionally discovered, orally bioavailable, potent, selective, small-molecule kinase activator of GCN2. HC-7366 has now progressed to Ph. I trials to treat ccRCC and AML. This case study is a fantastic example of how to mitigate CYP3A4 inhibition and improve oral bioavailability via judicious choice of salt formulation.
sovleplenib (HMPL-523)
Sovleplenib (HMPL-523) is an orally bioavailable Syk inhibitor being developed by HUTCHMED and is currently in Ph. II and Ph. III clinical trials for several autoimmune diseases. Derived from an HTS hit and SAR optimization, the discovery story of sovleplenib serves as an excellent case study on how to design a next-generation Syk inhibitor devoid of off-target kinase activity, mitigated hERG activity, and more.
AZD4144
Recently, a surge of (pre)clinical compounds inhibiting the NLRP3 inflammasome, often featuring a hexahydroindacene ring system, has emerged, including Nodthera’s ND-0796. In a push for new chemotypes, AZ and Mitsubishi Tanabe have disclosed their clinical compound, AZD4144, which is currently in Ph. I trials in healthy volunteers. The discovery story detailed their efforts to overcome PLD (phospholipidosis), genotoxicity, and hERG inhibition in a non-classical pharmacophore series. The discovery was presented by Anders Johansson at the EFMC-ISMC 2024 Meeting in Rome.
BMS-986408
BMS-986408 is an oral, dual DGK ⍺ and ζ inhibitor currently in a Ph. I/II trial in patients with solid tumors. The compound was identified stemming from a phenotypic screening approach, and subsequent target deconvolution revealed DGK to be the target. If approved, it would be a first-in-class intracellular checkpoint inhibitor of DGK. This is an excellent case study on how to overcome a DILI risk associated with BSEP inhibition, as well as how to improve solubility and PK properties of your compounds through the introduction of polarity, reduction of aromatic rings, and increase in f(sp3).