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 lines||HDMEC, OSCC3, UM-SCC-17B, UM-SCC-74A cells line|
|Preparation method||SRB assay
Sulforhodamine B (SRB) cytotoxicity assays were done as described (25). 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 (Sigma-Aldrich, St. Louis, MO) in 1% acetic acid, and plates were read in a microplate reader at 560 nm (GENios; Tecan, Graz, Austria). 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.
|Incubation time||72-96 h|
|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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Related Bcl-2 Products|
AZD-5991 Racemate is a Mcl-1 inhibitor with an IC50 of <3 nM in FRET assay.
|Bax inhibitor peptide V5
Bax inhibitor peptide V5 is a Bax-mediated apoptosis inhibitor.
Marinopyrrole A (Maritoclax) is a novel and specific Mcl-1 inhibitor with an IC50 value of 10.1 μM.
MIK665 is an inhibitor of induced myeloid leukemia cell differentiation protein (Mcl-1; Bcl2-L-3).
BDA-366 is a small molecule antagonist that specifically binds the BCL2 BH4 domain, and has the ability to convert anti-apoptotic BCL2 into a pro-apoptotic death molecule.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.