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.
|Related Bcl-2 Products|
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.
BH3I-1 is a Bcl-XL-BH3 domain interaction inhibitor with Ki of 2.4 μM (by fluorescence polarization ).It is a selective inhibitor of Bcl-2 family proteins.
HA14-1 is a Bcl-2 inhibitor that is widely used for studies of apoptosis with IC50 of ~9 μM.
Sabutoclax(BI-97C1) is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.
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