Parrish, Karen E. published the artcilePharmacodynamics-based approach for efficacious human dose projection of BMS-986260, a small molecule transforming growth factor beta receptor 1 inhibitor, HPLC of Formula: 2001559-19-7, the publication is Biopharmaceutics & Drug Disposition (2021), 42(4), 137-149, database is CAplus and MEDLINE.
For decades, tumor biol. implicated TGF-β as an attractive therapeutic target due to its immunosuppressive effects. Toward this end, multiple pharmaceutical companies developed a number of drug modalities that specifically target the TGF-β pathway. BMS-986260 is a small mol., selective TGF-βR1 kinase inhibitor that was under preclin. development for oncol. In vivo studies across mouse, rat, dog, and monkey and cryopreserved hepatocytes predicted human pharmacokinetics (PK) and distribution of BMS-986260. Efficacy studies of BMS-986260 were undertaken in the MC38 murine colon cancer model, and target engagement, as measured by phosphorylation of SMAD2/3, was assessed in whole blood to predict the clin. efficacious dose. The human clearance is predicted to be low, 4.25 mL/min/kg. BMS-986260 provided a durable and robust antitumor response at 3.75 mg/kg daily and 1.88 mg/kg twice-daily dosing regimens. Phosphorylation of SMAD2/3 was 3.5-fold less potent in human monocytes than other preclin. species. Taken together, the projected clin. efficacious dose was 600 mg QD or 210 mg BID for 3 days followed by a 4-day drug holiday. Mechanism-based cardiovascular findings in the rat ultimately led to the termination of BMS-986260. This study describes the preclin. PK characterization and pharmacodynamics-based efficacious dose projection of a novel small mol. TGF-βR1 inhibitor.
Biopharmaceutics & Drug Disposition published new progress about 2001559-19-7. 2001559-19-7 belongs to pyridazine, auxiliary class TGF-beta/Smad,TGF-beta Receptor, name is 6-(4-(3-Chloro-4-fluorophenyl)-1-(2-hydroxyethyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazine-3-carbonitrile, and the molecular formula is C18H12ClFN6O, HPLC of Formula: 2001559-19-7.
Referemce:
https://en.wikipedia.org/wiki/Pyridazine,
Pyridazine | C4H4N2 – PubChem