With the popular success of diabetes and weight-loss peptide drugs from Novo (e.g. semaglutide/Ozempic), this month features a pair of ultra-hot non-peptide oral GLP-1R modulators in clinical development. Other notable Molecules of the Month include vorasidenib, which demonstrated headline-generating efficacy in brain cancers, as well as controversial billion-dollar molecule atrasentan, the subject of a short-seller report by Muddy Waters. We’ll have more detailed case studies on these molecules coming soon, but in the meantime you can check out some recent articles about the following here:
orforglipron - A non-peptide GLP-1R agonist in Phase III clinical trials for obesity and type 2 diabetes, identified through high-throughput screening, with origins from Chugai and developed now by Lilly.
danuglipron - An oral GLP-1-RA full agonist in Phase IIb clinical trials for obesity and Phase II trials for type 2 diabetes mellitus, identified through sensitized cell high-throughput screening and optimization, originated from Pfizer.
vorasidenib - An oral first-in-class dual IDH1/IDH2 inhibitor with efficacy in Phase III trials for IDH-mutant grade 2 gliomas, discovered through structure-based drug design (SBDD) of a prior mIDH inhibitor, developed by Agios and Servier.
atrasentan - An oral ETA receptor antagonist in Phase III clinical trials for IgA nephropathy and Phase II trials for Alport Syndrome, designed based on prior non-peptide ETA receptor antagonists, originated from Abbott Labs (AbbVie) and developed by Chinook Therapeutics (and now acquired by Novartis).
lirafugratinib (RLY4008) - An oral covalent FGFR2 inhibitor in Phase II trials for cholangiocarcinoma, designed through rational design and molecular dynamic simulations by Relay Therapeutics.
FLX475 - An oral CCR4 antagonist in Phase II trials for immunooncology, discovered through optimization of prior CCR4 ligands, from RAPT Therapeutics.
PCO371 - An oral PTH1R agonist in preclinical development for parathyroid hormone disorders, identified through a functional screen against cells expressing hPTHR1, with origins from Chugai.
GNE-7883 - A preclinical pan-TEAD inhibitor showing efficacy in xenograft models, discovered through TEAD3-YAP TR-FRET high-throughput screening of more than 2 million compounds by Genentech.
"compound 13" - A DCAF1 binder applied to targeted protein degradation, identified through high-throughput screening and optimization by Novartis.
CT3 - An irreversible trypanosomal topoisomerase II inhibitor, showing preclinical efficacy in mouse Chagas disease and sleeping sickness models, discovered through a phenotypic screen against trypanosomes by Novartis (NITD).
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