AZD5153 6-hydroxy-2-naphthoic acid

製品コードS8344 バッチS834401

印刷

化学情報

Chemical Structure Synonyms AZD5153 HNT salt Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H33N7O3.C11H8O3
分子量 667.75 CAS No. 1869912-40-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (149.75 mM)
Ethanol 27 mg/mL warmed with 50ºC water bath (40.43 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AZD5153 6-hydroxy-2-naphthoic acid (HNT salt) is a potent, selective, and orally available BET/BRD4 bromodomain inhibitor with pKi of 8.3 for BRD4. AZD5153 inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes. NSD3, via H3K36me2, acts as an epigenetic deregulator to facilitate the expression of oncogenesis-promoting genes.
in vitro

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[1].
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[1]. 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[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MV-4-11, MM.1S, and K562 cells
濃度 --
反応時間 48 h
実験の流れ

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.
動物実験 動物モデル Female CB17 SCID and SCID beige mice
投薬量 --
投与方法 by oral gavage mini-pump infusion or s.c

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

BRD4 inhibition impairs DNA mismatch repair, induces mismatch repair mutation signatures and creates therapeutic vulnerability to immune checkpoint blockade in MMR-proficient tumors [ J Immunother Cancer, 2023, 11(4)e006070] PubMed: 37072347
Dual blockade of BRD4 and ATR/WEE1 pathways exploits ARID1A loss in clear cell ovarian cancer [ Res Sq, 2023, 10.21203/rs.3.rs-3314138/v1] PubMed: 37841875
AZD5153 reverses palbociclib resistance in ovarian cancer by inhibiting cell cycle-related proteins and the MAPK/PI3K-AKT pathway [ Cancer Lett, 2022, 528:31-44] PubMed: 34942306
Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumor [ Mol Cancer Ther, 2022, molcanther.MCT-21-0646-A.2021] PubMed: 35247919
Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection [ Microbiol Spectr, 2022, 10(4):e0241921] PubMed: 35758684
Single-cell resolved imaging reveals intra-tumor heterogeneity in glycolysis, transitions between metabolic states, and their regulatory mechanisms [ Cell Rep, 2021, 34(7):108750] PubMed: 33596424
Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor [ Pediatr Blood Cancer, 2021, e29401] PubMed: 34693628
BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor. [ Int J Biol Sci, 2019, 15(9):1942-1954] PubMed: 31523195
Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study [ Oncologist, 2019, 24(8):e740-e748] PubMed: 30696721
The DNA Endonuclease Mus81 Regulates ZEB1 Expression and Serves as a Target of BET4 Inhibitors in Gastric Cancer. [ Mol Cancer Ther, 2019, 18(8):1439-1450] PubMed: 31142662

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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