AT-101

• CAT Number: I005398
• CAS Number: 90141-22-3
• Molecular Formula: C30H30O8
• Molecular Weight: 518.562
• Purity: ≥95%
• Target: Bcl-2 Family
• Solubility: DMSO >80 mg/ml Ethanol >80 mg/ml
• Storage: Store at -20°C
• IC50: 0.32/0.48/0.18 uM for Bcl-2/Bcl-xL/Mcl-1
• IUPAC Name: 7-(8-formyl-1,6,7-trihydroxy-3-methyl-5-propan-2-ylnaphthalen-2-yl)-2,3,8-trihydroxy-6-methyl-4-propan-2-ylnaphthalene-1-carbaldehyde
• InChI: InChI=1S/C30H30O8/c1-11(2)19-15-7-13(5)21(27(35)23(15)17(9-31)25(33)29(19)37)22-14(6)8-16-20(12(3)4)30(38)26(34)18(10-32)24(16)28(22)36/h7-12,33-38H,1-6H3
• InChIKey: QBKSWRVVCFFDOT-UHFFFAOYSA-N
• SMILES: CC1=C(C(=C2C(=C1)C(=C(C(=C2C=O)O)O)C(C)C)O)C3=C(C=C4C(=C3O)C(=C(C(=C4C(C)C)O)O)C=O)C

AT101, the R-(-) enantiomer of Gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.32 μM, 0.48 μM and 0.18 μM.IC50 Value: 0.32/0.48/0.18 uM for Bcl-2/Bcl-xL/Mcl-1Target: Bcl-2; Bcl-xl; Mcl-1AT-101 is orally bioavailable solvate of R-(-)-enantiomer of gossypol with potential antineoplastic activity. As a BH3 mimetic, AT-101 binds to the hydrophobic surface binding groove BH3 of the anti-apoptotic proteins Bcl-2 and Bcl-xL, blocking their heterodimerization with pro-apoptotic members of the Bcl-2 family of proteins such as Bad, Bid, and Bim; this may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. AT-101 induces apoptosis in vitro through activation of caspase-9; cytotoxic to multiple myeloma and drug-resistant cell lines. AT-101 delays onset of androgen-independent growth of VCaP prostate cancer xenografts in vivo.

Reference

[1]. Loberg RD, McGregor N, Ying C et al. In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia. 2007 Dec;9(12):1030-7.
[2]. Kline MP, Rajkumar SV, Timm MM et al. R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells. Exp Hematol. 2008 May;36(5):568-76.
[3]. Balakrishnan K, Burger JA, Wierda WG, Gandhi V. AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance. Blood. 2009 Jan 1;113(1):149-53.
[4]. Moretti L, Li B, Kim KW et al. AT-101, a pan-Bcl-2 inhibitor, leads to radiosensitization of non-small cell lung cancer. J Thorac Oncol. 2010 May;5(5):680-7.
[5]. R-(-)-gossypol acetic acid
[6]. McGregor N, Patel L, Craig M et al. AT-101 (R-(-)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model. J Cell Biochem. 2010 Aug 1;110(5):1187-94.