A-385358

• CAT Number: I020440
• CAS Number: 406228-55-5
• Molecular Formula: C₃₂H₄₁N₅O₅S₂
• Molecular Weight: 639.83
• Purity: ≥95%
• Target: Bcl-2 Family
• IUPAC Name: N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-(4,4-dimethylpiperidin-1-yl)benzamide
• InChI: 1S/C32H41N5O5S2/c1-32(2)17-20-36(21-18-32)26-12-10-24(11-13-26)31(38)34-44(41,42)28-14-15-29(30(22-28)37(39)40)33-25(16-19-35(3)4)23-43-27-8-6-5-7-9-27/h5-15,22,25,33H,16-21,23H2,1-4H3,(H,34,38)/t25-/m1/s1
• InChIKey: DWEHITNKTMMZBR-RUZDIDTESA-N
• SMILES: CC1(CCN(CC1)C2=CC=C(C=C2)C(=O)NS(=O)(=O)C3=CC(=C(C=C3)N[C@H](CCN(C)C)CSC4=CC=CC=C4)[N+](=O)[O-])C

A-385358 (CAT: I020440) is a selective inhibitor of Bcl-XL, a member of the Bcl-2 family of proteins that regulate apoptosis. It exhibits a strong affinity for Bcl-XL with a Ki of 0.80 nM and moderate affinity for Bcl-2 with a Ki of 67 nM in fluorescence polarization assays. Treatment of IL-3-deprived FL5.12/Bcl-XL cells with A-385358 results in cell killing accompanied by increased caspase-3 activity, indicating its pro-apoptotic effect. A-385358 shows a higher potency in inducing cytochrome c release from mitochondria in FL5.12/Bcl-XL cells compared to FL5.12/Bcl-2 cells, further supporting its selective action on Bcl-XL.

Reference

[1]. Shoemaker AR, et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res. 2006 Sep 1;66(17):8731-9.