| Identification | Back Directory | [Name]
Tube2156 | [CAS]
2882165-79-7 | [Synonyms]
CFT1946
Tube2156
N′-[2-Cyano-4-fluoro-3-[[3-[(3R)-8-[2-[1-[5-fluoro-1-methyl-3-(tetrahydro-2,4-dioxo-1(2H)-pyrimidinyl)-1H-indazol-6-yl]-4-hydroxy-4-piperidinyl]acetyl]-1-oxa-8-azaspiro[4.5]dec-3-yl]-3,4-dihydro-4-oxo-6-quinazolinyl]oxy]phenyl]-N-ethyl-N-methylsulfamide | [Molecular Formula]
C45H49F2N11O9S | [MOL File]
2882165-79-7.mol | [Molecular Weight]
958.01 |
| Chemical Properties | Back Directory | [density ]
1.56±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
6.21±0.50(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
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[1][2]. | [in vivo]
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].
| Animal Model: | BRAFV600E A375 xenograft mouse model[2] | | Dosage: | 0.3, 3, 10 mg/kg | | Administration: | PO; BID; 20 days | | Result: | Shows dose-dependent tumor regression.
10 mg/kg BID dose resulted in sustained tumor regression and is the minimum efficacious dose.
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| [IC 50]
Cereblon; BRafV600E | [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. |
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