PROTAC BRAF-V600E degrader-1

• CAT Number: I042931
• CAS Number: 2417296-84-3
• Molecular Formula: C48H54F2N10O10S
• Molecular Weight: 1001.07
• Purity: ≥95%
• Synonyms: N-[3-[5-[[1-[3-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]propanoyl]piperidin-4-yl]-methylamino]-3-pyrimidin-5-ylpyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]propane-1-sulfonamide
• InChI: InChI=1S/C48H54F2N10O10S/c1-3-25-71(66,67)56-36-8-7-34(49)45(43(36)50)59-28-33(30-26-51-29-52-27-30)44-37(59)9-11-39(54-44)57(2)31-13-17-58(18-14-31)41(62)15-19-68-21-23-70-24-22-69-20-16-53-35-6-4-5-32-42(35)48(65)60(47(32)64)38-10-12-40(61)55-46(38)63/h4-9,11,26-29,31,38,53,56H,3,10,12-25H2,1-2H3,(H,55,61,63)
• InChIKey: FMUGAZVOOIUFAT-UHFFFAOYSA-N
• SMILES: CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)N2C=C(C3=C2C=CC(=N3)N(C)C4CCN(CC4)C(=O)CCOCCOCCOCCNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C8=CN=CN=C8)F

PROTAC BRAF-V600E degrader-1 is a potent PROTAC BRAF-V600E degrader with Kd value of 2.4 nM and 2 nM for BRAF and BRAF-V600E, respectively. PROTAC BRAF-V600E degrader-1 degrades BRAF-V600E via the ubiquitin-proteasome system (UPS). PROTAC BRAF-V600E degrader-1 can inhibit melanoma cell growth[1].
PROTAC BRAF-V600E degrader-1 (compound 23) (1 nM-10 μM; 72 h) inhibits the cell viability of A375 and HT-29[1].
PROTAC BRAF-V600E degrader-1 (1-1000 nM; 16 h or 0-24 h) inhibits p-ERK and BRAF-V600E protein in A375 cells[1].

Reference

[1]. Han XR, et al. Discovery of Selective Small Molecule Degraders of BRAF-V600E. J Med Chem. 2020 Apr 23;63(8):4069-4080.
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