ABT-737 is a potent and selective inhibitor of B-cell lymphoma-2 (BCL-2) family proteins. The ABT-737 single-agent LC90 values ranged from 100 nM for COG-LL-319 and RS4; 11 cells to low micromolar concentrations for the other five ALL cell lines. ABT-737 efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib. Moreover, we observed that the enhancement of ABT-737-mediated apoptosis by NCTD was associated with activation of mitochondrial apoptosis signaling pathway, which involved cytosolic release of cytochrome c, cleavage of caspase-9 and caspase-3. Finally, knockdown of Mcl-1 substantially potentiated ABT-737-mediated apoptotic cell death, confirming the potency of Mcl-1 repression by NCTD in enhancing ABT-737-induced apoptosis. These results therefore suggest that combination treatment with NCTD can overcome ABT-737 resistance and enhance ABT-737 therapeutic efficacy in treating human HCC.
|Source||Cancer Res (2014). Figure 4. ABT-737|
|Cell Lines||SCLC cell lines|
|Incubation Time||24 or 72 h|
|Results||We did observe that the proapoptotic proteins BAX and BAK were increased in both PDXs treated with rapamycin alone or in combination with ABT-737.|
|Source||Cancer Res (2014). Figure 3. ABT-737|
|Cell Lines||SCLC PDX models|
|Incubation Time||14 d|
|Results||Correlating these findings with transcriptional profiling data, we observed decreased levels of six HIF-1α–regulated genes in LX47 after treatment with ABT-737, this effect was less pronounced in LX33, but nonetheless, observed for most genes.|
|Cell lines||CLL cells and platelets|
|Preparation method||Apoptosis analysis Peripheral blood mononuclear cells were purified using Histopaque and cultured in RPMI 1640 medium supplemented with 10% fetal calf serum and 2 mmol/l L-glutamine at2*106 cells/ml. Cells were exposed to different concentrations of ABT-737, ABT-263, or ABT-199 for 4 h before analysis of apoptosis by externalisation of phosphatidylserine (PS) and binding of AnnexinV/fluorescein isothiocyanate (FITC). Platelets isolated from healthy volunteers were cultured in Hepes-buffered saline and exposed to different concentrations of ABT-737, ABT-263, or ABT-199 for 4 h before analysis of apoptosis in the CD41-positive population by externalisation of PS and binding of AnnexinV/FITC.|
|Incubation time||4 h|
|Animal models||C57BL/6 mice were injected (i.v.) with 3x106 T1 lymphoma cells|
|Formulation||formulated in 60% phosal 50PG (standardized phosphatidylcholine concentrate with at least 50% PC and propylene glycol|
|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 ≥150 mg/mL|
Norcantharidin enhances ABT-737-induced apoptosis in hepatocellular carcinoma cells by transcriptional repression of Mcl-1.
Zhang et al. Cell Signal. 2012 Sep;24(9):1803-9. PMID: 22609455.
MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex.
Konopleva et al. Leukemia. 2012 Apr;26(4):778-87. PMID: 22064351.
The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib.
Hikita et al. Hepatology. 2010 Oct;52(4):1310-21. PMID: 20799354.
|Related Bcl-2 Products|
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.
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.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.