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AZD5153
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。
AZD5153图片
CAS NO:1869912-39-9
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 479.59
Formula C25H33N7O3
CAS No.1869912-39-9 (free base)
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL (149.75 mM)
Water: <1 mg/mL
Ethanol: 27 mg/mL warmed (40.43 mM)
SMILESO=C1N(C)CCN(CCOC2=CC=C(C3CCN(C4=NN5C(C=C4)=NN=C5OC)CC3)C=C2)[C@@H]1C
SynonymsAZD-5153; AZD5153; AZD 5153.
实验参考方法
In Vitro

In vitro activity: Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously. AZD5153 treatment markedly affects transcriptional programs of MYC, E2F, and mTOR. Of note, mTOR pathway modulation is associated with cell line sensitivity to AZD5153. AZD5153 potently disrupts BRD4 foci in U2OS cells with an IC50 value of 1.7 nmol/L. AZD5153 efficiently downregulates MYC protein levels across the cell line panel irrespective of their sensitivity to AZD5153. AML, MM, and DLBCL cell lines are highly sensitive to AZD5153.


Kinase Assay: AZD-5153 HNT salt, the 6-Hydroxy-2-naphthoic acid salt form of AZD5153, is a potent, selective, and orally available BET/BRD4 (bromodomain and extraterminal) bromodomain inhibitor with pKi of 8.3 for BRD4 and possesses a bivalent binding mode. Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously. AZD5153 treatment markedly affects transcriptional programs of MYC, E2F, and mTOR. Of note, mTOR pathway modulation is associated with cell line sensitivity to AZD5153.


Cell Assay: Apoptosis was analyzed by flow cytometry using CellEvent Caspase 3/7 Green detection reagent. MV-4-11, MM.1S, and K562 cells were pretreated with AZD5153 or I-BET762 for 48 hours in culture media. Cells were collected and stained with 5 μmol/L final concentration of CellEvent for 30 minutes at 37°C. Flow cytometry was done on a BD Fortessa using the Blue laser and FITC filter set.

In Vivo In vivo administration of AZD5153 leads to tumor stasis or regression in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B-cell lymphoma. AZD5153 modulates MYC and HEXIM1 in AML xenograft tumors and human whole blood. AZD5153 is administered orally to mice bearing MV-4-11 xenografts, and pharmacodynamic activity (intratumoral levels of c-Myc) is measured at 2, 4, and 8 h postdose. A considerable decrease in c-Myc expression is observed out to 8 h post dose at free plasma levels of compound<0.2 μM. This decrease in c-Myc expression after treatment with AZD5153 is consistent with other published BET inhibitors
Animal model Female CB17 SCID and SCID beige mice
Formulation & Dosage 0.5% hydroxymethylcellulose, 0.1% Tween80 (oral); 20% v/v DMSO/60% v/v HP-B-CD in water (s.c);by oral gavage mini-pump infusion or s.c
References Mol Cancer Ther. 2016 Nov;15(11):2563-2574. Epub 2016 Aug 29; J Med Chem. 2016 Sep 8;59(17):7801-17.