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AT-101 (R-(-)-gossypol acetic acid) is a polyphenolic compound isolated from cottonseeds. AT-101 induces Apoptosis through activation of caspase-9, -3, and -7 in VCaP cells. It inhibits Bcl-2 by acting as a BH3 mimetic and disrupts the heterodimerization of Bcl-2 with proapoptotic family members. AT-101 was found to mimic the proapoptosis proteins and is able to bind to the BH3 domains of Bcl-2, Mcl-1, and Bcl-xL. AT-101 has been shown to be therapeutically active as a single agent in several mouse models including breast, prostate, colon, and non-small cell lung cancer. We demonstrate that AT-101 administration delays the onset of androgen-independent prostate cancer in vivo. The use of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer.
| Cell Experiment | |
|---|---|
| Cell lines | HDMEC, OSCC3, UM-SCC-17B, UM-SCC-74A cells line |
| Preparation method | SRB assay Sulforhodamine B (SRB) cytotoxicity assays were done as described. Briefly, cells were seeded at 2×103 cells per well of 96-well plates, allowed to attach overnight, and treated with AT101 and/or taxotere for 72–96 hours. Cells were fixed with 10% trichloroacetic acid, stained with 0.4% SRB (M11518) in 1% acetic acid, and plates were read in a microplate reader at 560 nm. Test results were normalized against initial plating density and drug-free controls. Data were obtained from triplicate wells per condition and is representative of three independent experiments. |
| Concentrations | 0~100µM |
| Incubation time | 72-96 h |
| Animal Experiment | |
|---|---|
| Animal models | SCID Mouse Model of Human Tumor Angiogenesis |
| Formulation | resuspended in carboxymethyl cellulose and sonicated for 30 minutes |
| Dosages | 10mg/kg daily or 70mg/kg weekly |
| Administration | orally |
| Molecular Weight | 518.56 |
| Formula | C30H30O8 |
| CAS Number | 90141-22-3 |
| Solubility (25°C) | DMSO Ethanol |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Bcl-2 Products |
|---|
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ABT-263 (Navitoclax) is a potent, orally bioavailable inhibitor of the antiapoptotic Bcl-2 family members Bcl-2, Bcl-x (L), and Bcl-w. |
| ABT-737
ABT-737 is a potent and selective inhibitor of B-cell lymphoma-2 (BCL-2) family proteins, in small cell lung cancer. |
| ABT-199
ABT-199 (Venetoclax) is a highly potent, orally bioavailable and BCL-2 inhibitor. ABT-199 is the first inhibitor targeting Bcl-2 and PPI. |
| TW-37
TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. |
| Apogossypolone
Apogossypolone (ApoG2) is a pan Bcl-2 inhibitor for Bcl-2, Bcl-XL and Mcl-1 with Ki of 35 nM, 660 nM and 25 nM, respectively. |
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