AZD5153 6-Hydroxy-2-naphthoic acid

SKU: orb1304138

Description

AZD5153 is a potent, triazolopyridazine-based dual BRD4 and BET bromodomain inhibitor. It is utilized in cancer research to probe BET protein function and has demonstrated antitumor activity in both cellular assays and in vivo models.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1869912-40-2
• MW: 667.75
• Purity: 98.36%
• Formula: C₂₅H₃₃N₇O₃·C₁₁H₈O₃
• SMILES: OC(=O)c1ccc2cc(O)ccc2c1.COc1nnc2ccc(nn12)N1CCC(CC1)c1ccc(OCCN2CCN(C)C(=O)[C@H]2C)cc1
• Target: Epigenetic Reader Domain
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (4.94 mM);DMSO:250 mg/mL (374.39 mM);Ethanol:26 mg/mL (38.94 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  FL-BRD4:5 nM
• In Vivo:
  AZD5153 modulates MYC and HEXIM1 in AML xenograft tumors and human whole blood. 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 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.
• In Vitro:
  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.
• Cell Research:
  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. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BD1-BRD4, AZD 5153, AZD-5153 6-Hydroxy-2-naphthoic acid, AZD5153 6-Hydroxy-2-naphthoic acid, AZD-5153 HNT, AZD-5153 HNT salt, AZD5153, AZD-5153, AZD5153 6 Hydroxy 2 naphthoic acid, AZD5153 6Hydroxy2naphthoic acid, FL-BRD4, Epigenetic Reader Domain, EpigeneticReaderDomain

Compound Identifiers

PubChem CID

118693658