AZD1152

Inhibitor of AURKB

Structure

Information

Protein target names: AURKB

Mechanism of action: Inhibitor

Recommended in-cell concentration:
Up to 100 nM
Primary References:

In Vitro Validations

Uniprot ID: Q96GD4
Target Class: Kinase
Target SubClass: cell cycle-regulated kinase
Potency: Ki
Potency Value: <1 nM
Potency Assay: AZD1152 (Compound 5), the prodrug for Compound 34 (AZD1152-HQPA), inhibits AURKB in vitro with an IC50 < 0.001 uM.
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes
Target aliases:
Aurora kinase B, STK5, STK12, STK1, ARK2, AIRK2, A ...

DOI Reference: 10.1021/jm061335f

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

AZD1152 is a phosphate pro-drug that is rapidly cleaved to the active alcohol. The active alcohol is a potent inhibitor of AURB and AURC. We have dosed AZD1152 in tumor xenograft models in mice using IP administration (100 mg/kg, dosed once daily for 3 consecutive days) and seen robust efficacy in sensitive models (e.g., Lymphoma DOOH2 cell line). The AZD1152 alcohol is significantly less active in P-gp- and BCRP-expressing cell lines, most likely due to drug efflux.

(last updated: 31 May 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

I would like to see a more comprehensive screen of this probe against more than 50 kinases to confirm its broad selectivity. IC50 is listed at 0.37 nM. It is ~3700-fold more selective for Aurora B over Aurora A. AZD1152-HQPA is the active metabolite of AZ1152.

(last updated: 7 Jun 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

AZD1152 is a phosphate prodrug designed for in vivo studies only. The active form is compound 34 in the corresponding J Med Chem paper, with Aurora B inhibition IC50 <1 nM and the corresponding functional effect in SW620 cells of IC50 17 nM. For in vitro, cell-based studies, Compound 34 should be used since cleavage of the phosphate in AZD1152 might not occur in a cellular system. The compound is very selective based on profiling in the Ambit kinome panel where less than 10 kinases (example EPHB6, FLT3 (more potent than Aurora B)), have a KD within 10X of that for Aurora B. Any kinase reported as an off target within 100X could have functional effect in cellular environment if the Km for ATP is large.

(last updated: 18 Aug 2016 )