Farnaby, William published the artcileBAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design, Safety of 2-Hydroxy-4-(4-methylthiazol-5-yl)benzonitrile, the publication is Nature Chemical Biology (2019), 15(7), 672-680, database is CAplus and MEDLINE.
Targeting subunits of BAF/PBAF chromatin remodeling complexes has been proposed as an approach to exploit cancer vulnerabilities. Here, we develop proteolysis targeting chimera (PROTAC) degraders of the BAF ATPase subunits SMARCA2 and SMARCA4 using a bromodomain ligand and recruitment of the E3 ubiquitin ligase VHL. High-resolution ternary complex crystal structures and biophys. investigation guided rational and efficient optimization toward ACBI1(I), a potent and cooperative degrader of SMARCA2, SMARCA4 and PBRM1. I induced anti-proliferative effects and cell death caused by SMARCA2 depletion in SMARCA4 mutant cancer cells, and in acute myeloid leukemia cells dependent on SMARCA4 ATPase activity. These findings exemplify a successful biophysics- and structure-based PROTAC design approach to degrade high profile drug targets, and pave the way toward new therapeutics for the treatment of tumors sensitive to the loss of BAF complex ATPases.
Nature Chemical Biology published new progress about 1448190-10-0. 1448190-10-0 belongs to thiazole, auxiliary class Thiazoles, name is 2-Hydroxy-4-(4-methylthiazol-5-yl)benzonitrile, and the molecular formula is C11H8N2OS, Safety of 2-Hydroxy-4-(4-methylthiazol-5-yl)benzonitrile.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica