Jiang, Liang published the artcileDesign, synthesis, and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation, Related Products of bromides-buliding-blocks, the main research area is Bcr Abl proteolysis targeting chimeric degrader gatekeeper mutation; ALL, acute lymphoblastic leukemia; CML; CML, chronic myeloid leukemia; CRBN, cereblon; Clinical resistance; Co-IP, co-immunoprecipitation; DR, degradation rate; Degradation; IC50, cellular inhibition; LSCs, leukemic stem cells; NMPA, National Medical Products Administration; PROTAC; PROTAC, proteolysis-targeting chimeric; Ph+, Philadelphia chromosome; T315I mutation; T315I, threonine 315 to isoleucine 315; TGI, tumor growth inhibition; VHL, von Hippel-Lindau; cIAP1, cellular inhibitor of apoptosis protein 1.
Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clin. challenge for the treatment of chronic myeloid leukemia (CML). Chem. degradation of Bcr-AblT315I protein has become a potential strategy to overcome drug resistance. Herein, we first described the design, synthesis, and evaluation of a new class of selective Bcr-AblT315I proteolysis-targeting chimeric (PROTAC) degraders based on GZD824 (reported as Bcr-AblT315I inhibitor by our group). One of the degrader 7o with 6-member carbon chain linkage with pomalidomide exhibits the most potent degradation efficacy with DR of 69.89% and 94.23% at 100 and 300 nmol/L, resp., and has an IC50 value of 26.8 ± 9.7 nmol/L against Ba/F3T315I cells. Further, 7o also displays substantial tumor regression against Ba/F3-Bcr-AblT315I xenograft model in vivo.
Acta Pharmaceutica Sinica B published new progress about Antiproliferative agents. 56523-59-2 belongs to class bromides-buliding-blocks, name is 15-Bromopentadecanoic acid, and the molecular formula is C15H29BrO2, Related Products of bromides-buliding-blocks.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary