AZD1332

AZD1332 : ATP competitive inhibitor of NTRK1 and NTRK2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 ratings)

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Probe AZD1332 is in the process of SERP review.

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Information

NTRK1
NTRK2

Inhibitor, ATP competitive

50-100 nM

More...

Probe Availability:

MedChemExpress

In Vitro Validations

Uniprot ID: P04629

Target Class: Kinase

Target SubClass: TK

Potency: IC 50

Potency Value: 2 nM

Potency Assay: AlphaScreen and HTRF phosphorylation assay

PDB ID for probe-target interaction (3D structure): --

Structure-activity relationship: yes

Target aliases:

High affinity nerve growth factor receptor, TRKA, ...

DOI Reference: 10.1021/jm800343j

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 FGFR1 24 nM

Probe Selectivity in Vitro:

In vitro selectivity profiling across a broad panel of 177 kinases (Millipore's Kinase Profiler) showed that 500 nM AZ-23 significantly inhibited (>75% inhibition) only a small subset of these enzymes: 24 nM (FGFR1), 52 nM (Flt3), 55 nM (Ret), 84 nM (MuSk), 99 nM (Lck)

Potency in cells, off target : EC50 FGFR1 41 nM

Probe Selectivity in Cell:

Cell selectivity (EC50): 4077 nM (IGF1R), >1000 nM (Aurora), >3000 (CSF1R), >5000 nM (InsR, Akt, p70S6k, GSK3b)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The two cited publications provide a range of biochemical, cell-based, and in vivo assays demonstrating NTRK1/2/3 inhibition. Biochemical and cellular potency is very high for this small kinase family, and selectivity for NTRK enzymes vs other kinases appears reasonable, with FGFR kinases notable off-targets. While explicit PK parameters were not reported in mice, doses of 50 or 100 mpk QD appear effective in strongly suppressing NTRK activity in vivo. PK data for AZD1332 in rat and dog are available, but additional PK/PD data might be necessary to choose an optimal dosing regimen for studies using these species.

(last updated: 10 Apr 2021 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

AZD1332 is an excellent selective Tropomyosin-related kinase A inhibitor, with proven in vitro and in vivo efficacy.

(last updated: 19 Apr 2021 )