LY3202626
low-dose CNS-penetrant BACE inhibitor 90% red. of CSF Aβ in Ph. II at 9.2 mg / discont. from opt. vs. CatD and dose red. of prior leads Journal of Medicinal Chemistry Eli Lilly, Indianapolis, US
Other molecules you may be interested in
RMC-9805
RMC-9805 is a first-in-class, covalent KRAS(G12D)(ON) molecular glue inhibitor from Revolution Medicines that uses a cyclophilin A (CypA)-recruiting tricomplex mechanism combined with a finely tuned aziridine covalent handle to inhibit the previously “undruggable” KRAS(G12D) mutant. Read our coverage of the discovery story, disclosed at the AACR 2024 meeting in San Diego, to discover how structural and modeling insights were key to engaging a poorly nucleophilic mutant Asp, how RMC-9805 synergizes with PD-1 inhibitors, and the progress this remarkable compound is making in the clinic.
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).
GB0139
What is it? GB0139 is a selective, inhaled inhibitor of galectin-3 and galectin-1 in Ph. II for IPF and COVID-19 pneumonitis, and is Galecto’s ($GLTO) lead asset. Galecto was founded in 2011 with Lund University academic galectin research leaders Ulf Nilsson and Hakon Leffler, and has had a research focus on galectin-3 modulators to treat [...]
Xanamem®
Xanamem® is Actinogen Medical's cortisol-blocking drug targeting the 11β-HSD1 (11β-hydroxysteroid dehydrogenase) enzyme.
VVD-130037
KEAP1 inhibition/NRF2 activation has been hotly pursued in recent years for immunology indications; however, in oncology, NRF2 degradation has been posited as a novel therapeutic mechanism for specific cancers. Vividion has already disclosed work on covalent KEAP1 inhibitors, but at the recent ACS Fall 2024 meeting, the structure and discovery story of their clinical oral covalent activator of KEAP1 were disclosed, identified through careful analysis of the data from their inhibitor screen.
