PROTAC B-Raf degrader 1

• CAT Number: I019393
• CAS Number: 2364367-27-9
• Molecular Formula: C36H37N5O12S
• Molecular Weight: 763.77
• Purity: ≥95%
• Synonyms: N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethyl]-2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetamide
• InChI: InChI=1S/C36H37N5O12S/c1-50-21-15-28(52-3)22(29(16-21)53-4)12-13-54(48,49)19-20-8-10-27(51-2)25(14-20)37-17-31(43)38-18-32(44)39-24-7-5-6-23-33(24)36(47)41(35(23)46)26-9-11-30(42)40-34(26)45/h5-8,10,12-16,26,37H,9,11,17-19H2,1-4H3,(H,38,43)(H,39,44)(H,40,42,45)/b13-12+
• InChIKey: AMOFJSISJOOLNX-OUKQBFOZSA-N
• SMILES: COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)NCC(=O)NC3=CC=CC4=C3C(=O)N(C4=O)C5CCC(=O)NC5=O

PROTAC B-Raf degrader 1 (compound 2) is a proteolysis targeting chimera (PROTAC) for the degradation of B-Raf based on Cereblon ligand with anti-cancer activity[1].
The IC50 values of PROTAC B-Raf degrader 1 (compound 2) towards MCF-7, MDA-MB-231, HepG2, LO2 and B16 cells are 2.7 μM, 21.21 μM, 18.70 μM, 41.11μM and 22.68 μM, respectively[1].?
PROTAC B-Raf degrader 1 (5 or 10 μM) can accelerate the degradation of B-Raf by recruiting ubiquitin-proteasome system, and further affects the expression of Mcl-1, a downstream protein of B-Raf[1].?
MCF-7 cells achieve an apoptosis rate of 76.70% (64.00% early apoptosis, 12.70% late apoptosis) after 24 h incubation of PROTAC B-Raf degrader 1 with the concentration of 20 μM[1].?
PROTAC B-Raf degrader 1 arrests cell cycle at the G2/M phase[1].

Reference

[1]. Chen H, et al. Pomalidomide hybrids act as proteolysis targeting chimeras: Synthesis, anticancer activity and B-Raf degradation. Bioorg Chem. 2019 Mar 19;87:191-199.
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