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Birabresib(OTX015 MK8628)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Birabresib(OTX015 MK8628)图片
CAS NO:202590-98-5
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)491.99
FormulaC25H22ClN5O2S
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

MK-8628; MK 8628; Birabresib; OTX015; OTX-015; MK8628; OTX 015

Chemical Name: (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide.

SMILES Code: O=C(NC1=CC=C(O)C=C1)C[C@H]2C3=NN=C(C)N3C4=C(C(C)=C(C)S4)C(C5=CC=C(Cl)C=C5)=N2

实验参考方法
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 VivoOTX015 (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 modelBLAB/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.