An oral, potentially CNS-penetrant BTK inhibitor for multiple sclerosis, a reversible pan-KRAS inhibitor, and a squaramide-containing clinical candidate are just some of the examples for this month's MOTM.
Stay tuned for the full case studies which will cover why the molecules matter, how they were discovered, the key steps behind optimization, how they work, why the targets were chosen, any interesting toxicology and clinical data, and more.
In the meantime, you can find recent news and articles that inspired us to write up these stories below:
- fenebrutinib - An oral BTK inhibitor that recently demonstrated efficacy in multiple sclerosis from Genentech, and is now entering Ph. III
- BI-2493 - An oral, reversible pan-KRAS inhibitor with oral activity in xenograft models identified from a prior covalent KRAS(G12C) inhibitor by Boehringer Ingelheim, Vienna, Austria
- PF-07054894 - An oral, insurmountable, selective CCR6 antagonist in Phase I clinical trials for ulcerative colitis identified from directed screening for novel negative allosteric modulators by Pfizer, Cambridge, MA.
- ziritaxestat - An oral ATX inhibitor with negative outcomes in Phase III in IPF (200-600 mg QD) identified from HTS and optimization by Galapagos SASU, Romainville, FR.
- OBI-3424 - An IV AKR1C3-activated cytotoxin prodrug in Phase I/II clinical trials in advanced solid tumors identified as a prodrug of DNA cross-linking agent, originally from Threshold Pharma, South San Francisco, CA and developed by OBI Pharma, Taipei, TW
- TAK-994 - An oral, brain-penetrant OX2R agonist that was discontinued for a liver safety signal after Phase II for narcolepsy, from Takeda, Fujisawa, JP.
- ritlecitinib - An oral, dual JAK3/TEC kinase inhibitor in Phase III for alopecia areata identified through structure-based design from tofacitinib by Pfizer, Groton, CT.
- LY03005 - An oral serotonin-norepinephrine-dopamine reuptake inhibitor approved in China for major depressive disorder identified from a serotonin-norepinephrine reuptake inhibitor, desvenlafaxine by Shandong Luye Pharmaceutical Co., Yantai, CN.
- TP0472993 - An oral 20-hydroxyeicosatetraenoic acid synthesis inhibitor with preclinical efficacy in a mouse kidney fibrosis model identified from an in-house screen and optimization by Taisho Pharmaceutical Co., JP.
- VK2809 - An oral THR agonist prodrug with positive Phase II data in NASH and thyroid hormone mimetic prodrug identified by Metabasis, La Jolla, CA and developed by Viking Therapeutics, San Diego, CA.