GSK1324726A (I-BET726) is a highly selective inhibitor of BET family proteins with IC50 of 41 nM, 31 nM, and 22 nM for BRD2, BRD3, and BRD4, respectively. GSK1324726A inhibits cell growth and induces cytotoxicity in neuroblastoma cell lines. GSK1324726A also modulates expression of genes involved in apoptosis, signaling, and MYC-family pathways, including the direct suppression of BCL2 and MYCN.
In vivo, in the mouse SK–N-AS and CHP-212 models, GSK1324726A (15 mg/kg p.o.) results in tumor growth inhibition and down-regulation MYCN and BCL2 expression.  In a mouse septic shock model, GSK1324726A (10 mg/kg i.v.) shows potent anti-inflammatory effects, and prevents death of diseased animals.
|Animal models||Xenograft models of non-MYCN-amplified and MYCN-amplified neuroblastoma in immunocompromised mice using the SK–N-AS and CHP-212 cell lines|
|Formulation||Suspended in 1% methylcellulose|
|Dosages||15 mg/kg once daily|
|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: ≥ 43 mg/mL|
The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor.
Gosmini R, et al. J Med Chem. 2014 Oct 9;57(19):8111-31. PMID: 25249180.
BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models.
Wyce A, et al. PLoS One. 2013 Aug 23;8(8):e72967. PMID: 24009722.
|Related Epigenetic Reader Domain Products|
AZD5153 is a potent bivalent triazolopyridazine based Bromodomain and Extraterminal (BET) Inhibitor, with IC50 value of 5 nM.
MS417 (also known as GTPL7512) is a potent and selective BRD4 inhibitor, which binds to BRD4-BD1 and BRD4-BD2 with IC50s of 30 and 46 nM, respectively.
FL-411 is a selective BRD4 inhibitor.
dBET6 is a highly potent, selective and cell-permeable degrader of BET with an IC50 of 14 nM.
dBET1 is a potent BRD4 protein degrader with an EC50 of 430 nM.
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