Home JAK/STAT JAK inhibitor AZ 960

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AZ 960 JAK inhibitor

Cat.No.S2214

AZ 960 is a novel ATP competitive JAK2 inhibitor with IC50 and Ki of <3 nM and 0.45 nM, 3-fold selectivity of this compound for JAK2 over JAK3. This chemical induces apoptosis and growth arrest.
AZ 960 JAK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 354.36

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Quality Control

Batch: S221401 DMSO]71 mg/mL]false]Ethanol]3 mg/mL]false]Water]Insoluble]false Purity: 99.05%
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  • NMR
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99.05

Solubility

In vitro
Batch:

DMSO : 71 mg/mL (200.36 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 354.36 Formula

C18H16F2N6

 Storage (From the date of receipt)
CAS No. 905586-69-8 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=CC(=NN1)NC2=C(C=C(C(=N2)NC(C)C3=CC=C(C=C3)F)C#N)F

Mechanism of Action

Targets/IC50/Ki
JAK2
0.45 nM(Ki)
JAK2
<3 nM
In vitro
AZ960 also inhibits many kinases less than 50% at a concentration of 0.1 μM such as JAK3 (IC50=9 nM), TrkA, Aurora, and ARK5. In cells, this compound 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 (TEL-JAK1, -JAK3, and -TYK2). It shows potent activity in inhibiting the proliferation of the TEL-JAK2, -JAK1, -JAK3, and -Tyk2 cell lines with GI50 values of 25 nM, 230 nM, 279 nM, and 214 nM, respectively. Moreover, this chemical also potently inhibits SET-2 cell proliferation with an average GI50 of 33 nM by reducing both STAT3 and STAT5 phosphorylation levels. It causes growth arrest and apoptosis of human T-cell lymphotropic virus type 1, HTLV-1pe 1, HTLV-1LV-1osis of human T-cSET-2 cell proliferation witBcl-xL by small interfering RNA potentiates anti-proliferative effects of AZ 960 in MT-1 cells. A recent study shows that this compound leads to significant inhibition of the clonogenic growth and induction of apoptosis of freshly isolated AML cells from patients.
Kinase Assay
Enzyme Biochemical Assay and Kinase Profiling
Inhibition studies of AZ 960 are performed using a recombinant JAK2 kinase (amino acids 808–1132) at a peptide (Tyk2 peptide) concentration of 100 nM and an ATP concentration of 15 μM. Concentrations of this compound ranging from 0.003 μM to 30 μM are used. The mode of inhibition and inhibition constant (Ki) of this compound against JAK2 kinase are further evaluated by inhibition kinetics. Specifically, a series of JAK2-catalyzed reactions are set up in HEPES buffer (75 mM, pH 7.3) with a fixed concentration of peptide (FL-Ahx-IPTSPITTTYFFFKKK-COOH), and varied concentrations of ATP and this chemical. The progress of each reaction is subsequently monitored by the Caliper LC3000 system, and the initial velocity of each reaction is extracted from the corresponding reaction time course. To define the mode of inhibition, initial velocities are plotted against corresponding ATP concentrations using Lineweaver-Burk plots and the characteristic convergence of the lines on the y axis demonstrates the competitiveness of this compound to ATP. Initial inspection of Ki using the Michealis-Menten equation revealed that this compound is a tight-binding inhibitor of JAK2. This chemical is profiled against 83 kinases at three inhibitor concentrations (0.01 μM, 0.10 μM, and 1.0 μM).
References

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