CFT1946 is an orally active, CRBN-based and mutant-selective bifunctional degradation activating compound (BiDAC™) degrader of BRAFV600E with a DC50 of 14 nM in A375 cells. CFT1946 is capable of degrading BRAF V600E (Class I), G469A (Class II), G466V (Class III) mutations, and the p61-BRAFV600E splice variant. CFT1946 can be used in tumor research.
CFT1946 (100 nM; 24 h) causes BRAFV600E degradation and inhibits MAPK Signaling with pERK loss in BRAFV600E cells but not in WT-BRAF cells[2].
CFT1946 (0.3-10 mg/kg; PO; BID; 20 days) induces tumor regression in the BRAFV600E A375 xenograft mouse model with 10 mg/kg[2].
References:
[1]. Sowa M E, et al. Preclinical evaluation of CFT1946 as a selective degrader of mutant BRAF for the treatment of BRAF driven cancers[J]. Cancer Research, 2022, 82(12_Supplement): 2158-2158. [2]. Yanke Liang. The Discovery and Characterization of CFT1946: A Potent, Selective, and Orally Bioavailable Degrader of Mutant BRAF for the Treatment of BRAF-driven Cancers. ANNUAL MEETING, American Association for Cancer Research, 2023.