This month features many molecules in Phase III clinical trials including Calcilytix’s CaSR antagonist for hypocalcemia and DalCor Pharma’s repurposed CETP inhibitor to treat cardiovascular disease. 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:
NVL-520 - an oral brain-penetrant ROS1-selective TKI in Phase I/II clinical trials for NSCLC and other solid tumors, designed through rational drug design (SBDD) from a known chemotype.
GDC-1971 (RLY-1971) - an oral allosteric SHP2 inhibitor in Phase I clinical trials for advanced or metastatic solid tumors, discovered through virtual screening with MD simulation based on known matter.
encaleret - oral CaSR antagonist (calcilytic) in Phase III clinical trials for ADH1, optimized from a known starting point derived from high throughput screening (HTS).
mezigdomide - oral cereblon-based IKZF1/3 degrader in Phase III clinical trials for relapsed and refractory multiple myeloma, identified through phenotypic screening and protein degradation assays against IKZF1 and 3.
BMS-986172 - oral MGAT2 inhibitor in Phase I clinical trials for obesity, optimized from a previous clinical candidate identified from high throughput screening (HTS) on human MGAT2.
dalcetrapib - CETP inhibitor thioester prodrug in Phase III clinical trials for cardiovascular diseases, repurposed as an HDL cholesterol modulator.
mavorixafor - oral allosteric CXCR4 inhibitor in Phase III NDA for WHIM syndrome, optimized from plerixafor.
tovorafenib - oral CNS-penetrant selective type II pan-RAF inhibitor in Phase III clinical trials for pediatric low-grade glioma, derived from a starting point from cell-based screening of small molecule RAF inhibitors. The drug was discovered by the medicinal chemistry group at Biogen and moved around a few times before becoming part of the Takeda/Day One collaboration.
AZD4604 - inhalable JAK-1 selective inhibitor in Phase II clinical trials for asthma, optimized from an oral JAK1 program starting from an HTS of the AstraZeneca collection against JAK1.
ABX-002 - TR-β selective CNS-penetrant TR-β agonist prodrug in Phase II clinical trials for major depressive disorder (MDD), starting from a known TR-beta agonist chemotype.
10/31/23 CORRECTION: Many thanks to Chris Helal and Claudio Chuaqui for pointing out that tovorafenib was originally discovered by the team at Biogen. The poster and text have been updated accordingly.
