BBT594

BBT594 (also known as NVP-BBT594) is a small molecule, type II kinase inhibitor originally developed by Novartis. It was initially designed to target the T315I-mutant BCR-ABL fusion protein for the treatment of drug-resistant chronic myeloid leukemia (CML). However, BBT594 was subsequently discovered to be a potent inhibitor of Janus kinase 2 (JAK2) and receptor tyrosine kinase RET. As a type II inhibitor, BBT594 binds to the inactive (DFG-out) conformation of the JAK2 kinase domain, occupying both the ATP-binding site and an adjacent hydrophobic pocket. This stabilizes the inactive state and prevents activation loop phosphorylation. Due to its poor pharmacokinetic properties and lack of selectivity, BBT594 is primarily utilized as a preclinical research tool to study JAK2-driven malignancies, such as myeloproliferative neoplasms (MPNs) and CRLF2-rearranged B-cell acute lymphoblastic leukemia (B-ALL), as well as RET-driven cancers.

Other names

5-((6-acetamidopyrimidin-4-yl)oxy)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)indoline-1-carboxamide5-[[6-(acetylamino)-4-pyrimidinyl]oxy]-2,3-dihydro-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-1H-indole-1-carboxamide