Obatoclax binds to members of the Bcl-2 protein family, preventing the binding of these anti-apoptotic proteins to the pro-apoptotic proteins Bax and Bak and so promoting the activation of the apoptotic pathway in Bcl-2-overexpressing cells. The Bcl-2 family of proteins (bcl-2, bcl-xl, bcl-w, and Mcl-1) are overexpressed in a wide variety of cancers, including those of the lymphatic system, breast, lung, prostate, and colon. Obatoclax prevents the interaction of these pro-survival proteins with Bax or Bak, thereby inducing apoptosis with up-regulation of Bim, induced cytochrome c release, and activation of caspase-3. Obstoclax also induces autophagy in mouse embryo fibroblasts and in HeLa cells.This compound inhibits the growth of cancer cell lines and primary cancer isolates. Obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies.
|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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||DMSO ≥80 mg/mL|
Combination of chloroquine and GX15-070 (obatoclax) results in synergistic cytotoxicity against pancreatic cancer cells.
Wang G, et al. Oncol Rep. 2014 Dec;32(6):2789-94. PMID: 25333301.
Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage.
Xie C, et al. Mol Oncol. 2014 Oct 2. PMID: 25308513.
Potential utility of the pan-Bcl-2 inhibitor GX15-070 (obatoclax) in cancer immunotherapy.
Kim PS, et al. Oncoimmunology. 2014 Jun 25;3:e29351. PMID: 25083341.
Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression.
Champa D, et al. Endocr Relat Cancer. 2014 Oct;21(5):755-67. PMID: 25012986.
Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis.
Nguyen M, et al. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19512-7. PMID: 18040043.
|Related Bcl-2 Products|
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.
A-1331852 is an orally available BCL-XL selective inhibitor with a Ki of less than 10 pM.
BTSA1 is a pharmacologically optimized BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis. It effectively promotes apoptosis in leukemia cell lines and patient samples while sparing healthy cells.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.