product name OTX015
Description: OTX015, also known as MK-8628, is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. OTX015 is the first BRD2/3/4 inhibitor to enter clinical trials. OTX015 showed antiproliferative activity in a large panel of cell lines derived from mature B-cell lymphoid tumors with median IC50 of 240 nmol/L, without significant differences among the different histotypes.
References: Oncotarget. 2015 Mar 20;6(8):5501-16; Mol Cancer Ther. 2013, 12, C244; Mol Cancer Ther. 2013, 12, A219.
491.99
Formula
C25H22ClN5O2S
CAS No.
202590-98-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 98 mg/mL (199.2 mM)
Water: <1 mg/mL
Ethanol: 98 mg/mL (199.2 mM)
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19419870
| In Vitro |
In vitro activity: OTX015 inhibits the binding of BRD2, BRD3, and BRD4 to AcH4 with IC50 ranging from 92 to 112 nM, and inhibits the growth of a variety of human cancer cell lines with GI50 ranging from 60 to 200 nM. OTX015 results in rapid down-regulation of c-MYC expression, and show the synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines. Kinase Assay: To assess binding of OTX015 to BRD2, BRD3, and BRD4, BRD-expressing CHO cell lysate (from CHO cells transfected with expression plasmids for Flag-tagged BRD2, BRD3, or BRD4 or vector alone), europium-conjugated anti-Flag antibody, XL-665-conjugated streptavidin, and biotinylated OTX015 were incubated at room temperature for 0.2 to 2h. Fluorescence was measured by TR-FRET using an EnVision 2103 Multilabel Reader and EC50 for binding was calculated by nonlinear regression using PRISM version 5.02. Using a similar system, the effect of OTX015 on binding of BRD2, BRD3, and BRD4 to acetylated histone H4 (AcH4) was evaluated by incubating biotin-conjugated -AcH4, BRD-expressing CHO cell lysate, europium-conjugated anti-Flag antibody, and XL-665-conjugated streptavidin. Fluorescence was measured by TR-FRET using an EnVision 2103 Multilabel Reader and percent binding was calculated by defining the value of the sample without biotin conjugate dAcH4 as 0% and the sample without OTX015 as 100%. The IC50 value was calculated by nonlinear regression using PRISM version 5.02. Cell Assay: Effects of OTX015 on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of OTX015 and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay. |
|---|---|
| In Vivo | OTX015 (p.o.) significantly inhibits the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79% at 100 mg/kg qd and 61% at 10 mg/kg bid, respectively. |
| Animal model | BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts. |
| Formulation & Dosage | 0, 10, 30 or 100 mg/kg qd or 10 mg/kg bid; oral gavage |
| References | Oncotarget. 2015 Mar 20;6(8):5501-16; Mol Cancer Ther. 2013, 12, C244; Mol Cancer Ther. 2013, 12, A219. |
