AZD-5153 6-hydroxy-2-naphthoic acid

Catalog No.S8344 Synonyms: AZD-5153 HNT salt

For research use only.

AZD-5153 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. AZD-5153 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.

AZD-5153 6-hydroxy-2-naphthoic acid Chemical Structure

CAS No. 1869912-40-2

Selleck's AZD-5153 6-hydroxy-2-naphthoic acid has been cited by 8 Publications

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

Biological Activity

Description AZD-5153 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. AZD-5153 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.
Targets
FL-BRD4 [1]
(Cell-based assay)
5 nM
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].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 Mlv6SpVv[3Srb36gZZN{[Xl? MYixPEBpenN? NYnZOHJGTGm|cHzhZ4Vu\W62IH;mJGhidG9vdHHn[4VlKGirc4TvcoUhUDNwMzDmdo9uKE6jbn;MeYMufGGpZ3XkJIZ2dGxibHXu[5RpKEKURESgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hUEOWMUG2JINmdGy|IHHmeIVzKDF6IHjyd{BjgSCQYX7vRnJGXCCjc4PhfeKhNCCLQ{WwJF0hOC5yMEWg{txONg>? MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDF7NUeyN{c,OjhzOUW3NlM9N2F-
HCT116 NYnBTolHTnWwY4Tpc44h[XO|YYm= M2LXR|E5KGi{cx?= MV7EbZNxdGGlZX3lcpQhd2ZiSHHsc{11[WepZXSgbIl{fG:wZTDIN{4{KG[{b32gUk11\XKvaX7hcEBP[W6xTIXjMZRi\2enZDDCVmQ1KGK{b33v[I9u[WmwIEGgLFQ1KHSxIEG2PEBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iSFPUNVE3KGOnbHzzJIFnfGW{IEG4JIhzeyCkeTDOZY5wSlKHVDDhd5NigcLiLDDJR|UxKD1iMT62JO69VS5? MlnmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjhzOUW3NlMoRjJ6MUm1O|I{RC:jPh?=
Assay
Methods Test Index PMID
Western blot NRG1 / BRD4 / GAPDH ; NRG1 / BRD4 / GAPDH ; NRG1 / BRD4 / GAPDH ; BRD4 / C-MYC / GAPDH ; cle-PARP / cle-caspase3 / GAPDH ; Wee1 / CDK1 / p-CDK1 / GAPDH 30036377 31523195
Growth inhibition assay Tumor Volume / Body Weight 29636547
IHC cle-caspase3 / cle-PARP / Ki-67 31523195
Immunofluorescence CDC6 p-S54 29636547
ELISA IL-10 / IL-12 32184777
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].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: MV-4-11, MM.1S, and K562 cells
  • Concentrations: --
  • Incubation Time: 48 h
  • Method:

    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)
Animal Research:

[1]

  • Animal Models: Female CB17 SCID and SCID beige mice
  • Dosages: --
  • Administration: by oral gavage mini-pump infusion or s.c
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(149.75 mM)
Water Insoluble
Ethanol ''''''27 mg/mL warmed

* 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.

Chemical Information

Molecular Weight 667.75
Formula

C25H33N7O3.C11H8O3

CAS No. 1869912-40-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1C(=O)N(CCN1CCOC2=CC=C(C=C2)C3CCN(CC3)C4=NN5C(=NN=C5OC)C=C4)C.C1=CC2=C(C=CC(=C2)O)C=C1C(=O)O

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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03205176 Completed Drug: AZD5153|Drug: Olaparib Malignant Solid Tumors|Lymphoma|Ovarian Cancer|Breast Cancer|Pancreatic Cancer|Prostate Cancer AstraZeneca June 30 2017 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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