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AZD9496

AZD9496 : ESR1 antagonist

Structure

Information

  • ESR1
  • Antagonist
  • < 10 nM

In Vitro Validations

Uniprot ID: P03372
Target Class: Other
Target SubClass: NR3 Subfamily
Potency: pIC50
Potency Value: 9.17 (0.8 nm)
Potency Assay: ERα LanthaScreen Assay to Measure ERα Binding
PDB ID for probe-target interaction (3D structure): 5ACC
Structure-activity relationship: yes
Target aliases:
Estrogen receptor, NR3A1, ESR, ESR1, ESR1_HUMAN, E ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

High selectivity of AZD9496 over other tested nuclear hormone receptors: androgen receptor (AR), IC50 = 30 μM; glucocorticoid receptor (GR), IC50 = 9.2 μM; progesterone receptor (PR), IC50 = 0.54 μM (cf. estrogen receptor (ERα), IC50 = 0.0008 μM).

Probe Selectivity in Cell:

No significant growth inhibition was seen in any ER− cell lines (EC50 > 10 μmol/L) in contrast to the low nanomolar activity seen in a range of ER+ cell lines.

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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 7 Jul 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

The compound AZD9496 was the lead candidate for orally bioavailable selective estrogen receptor downregulator (SERD) with equivalent potency and preclinical pharmacology to the intramuscular SERD fulvestrant.  Most recently, the compound was put on clinical hold and replaced by AZD9833, a backup compound with a superior profile for safety and efficacy.  In addition, there is excellent cellular data using two cell lines (MCF-7 and CAMA-1) for AZD9833.  AZD9496 should be replaced by AZD9833 as the chemical probe; it still possesses very good properties can be used as a secondary probe.

(last updated: 27 Jul 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 6 Sept 2021 )