AZ-960

AZ-960 : ATP competitive inhibitor of JAK2

Structure

Information

  • JAK2
  • Inhibitor, ATP Competitive
  • 100-500 nM

In Vitro Validations

Uniprot ID: O60674
Target Class: Kinase
Target SubClass: TK
Potency: Ki, IC50
Potency Value: 0.45 nM (Ki); 3 nM (IC50) @ Km ATP
Potency Assay: Enzymatic Biochemical Competitive Assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Tyrosine-protein kinase JAK2, JAK2, JAK2_HUMAN, JA ...

DOI Reference: 10.1074/jbc.M803813200

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : IC50 3 fold over JAK3
Probe Selectivity in Vitro:

AZ960 inhibited 11 kinases by greater than 50% at a concentration of 0.1 μm and 31 of 83 kinases less than 50% at a concentration 0.1 µM.

Potency in cells, off target : GI50 TEL-JAK1 230±74 nM, TEL-JAK3 279±29 nM, TEL-Tyk2 214±151 nM
Potency assay, off target (cells): Anti-Proliferation assay using BIOSOURCE AlamarBlue Assay
Probe Selectivity in Cell:

15–30-fold selectivity for TEL-JAK2-driven STAT5 phosphorylation compared with cell lines driven by other JAK kinase family members (TEL-JAK1, -JAK3, and -TYK2)

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SERP ratings and comments


SERP Ratings

In Cell Rating

(last updated: 12 Sept 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

AZ 960 is a moderately selective, ATP competitive JAK2 inhibitor with IC50 of <3 nM and a 3-fold selectivity over JAK3. It has been tested in a panel of 83 protein kinases at three inhibitor concentrations (0.01, 0.10, and 1.0 uM). AZ960 inhibited 11 kinases greater than 50% at a concentration of 0.1 uM. No reports of any additional off target profiling has been found. AZ960 is extensively profiled in various cellular assays at various levels with temporal control: o In a “close to target assay”, AZ 960 inhibits the phosphorylation of STAT5 in TEL-JAK2 cells with an average IC50 of 15 nM and exhibits 15-30 -fold sensitivity for TEL-JAK2-driven STAT5 phosphorylation compared with cell lines driven by other JAK kinase family members. o In a “proximal response assay” (after gene regulation), AZ960 inhibits BCL-XL gene expression as well as Pim1 and Pim2 expression (known to be regulated by BCL-XL) in SET-2 Cells. o In a “phenotypic assay”, AZ960 dose dependently inhibited SET-2 cell proliferation (after inhibition of STAT3/5 phosphorylation). AZ960 has not been reported to be used in any model organisms. However, several other JAK2 inhibitors are available with various selectivity profiles of which several have reported in vivo data (even clinical data). Many JAK2 inhibitors with various potency and selectivity profiles exists of which many have been used as pharmacological in vivo tools. There is to my knowledge no public information about the use of AZ-960 in any model organisms. Several of JAK2 inhibitors are in the chemical probes portal.

(last updated: 12 Oct 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

The compound shows only 3-fold selectivity over JAK3. Potentially pan-selective inhibitor. Not screened against all kinases. No target engagement data is available

(last updated: 22 Mar 2023 )