420099

JAK Inhibitor I

JAK Inhibitor I, CAS 457081-03-7, is a potent, reversible, cell-permeable, and ATP-competitive inhibitor of JAK 1 (IC₅₀ = 15 nM), JAK2 (IC₅₀ = 1 nM), JAK3 (K_i = 5 nM) and Tyk2 (IC₅₀ = 1 nM).

• Synonym(s): JAK Inhibitor I, 2-(1,1-Dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinolin-7-one, Pyridone 6, P6, DBI, JAK1 Inhibitor I, JAK2 Inhibitor I, JAK3 Inhibitor X
• Empirical Formula (Hill Notation): C₁₈H₁₆FN₃O
• CAS Number: 457081-03-7
• Molecular Weight: 309.34
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 5 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• InChI: 1S/C18H16FN3O/c1-18(2,3)17-21-14-10-5-4-9(19)8-12(10)13-11(15(14)22-17)6-7-20-16(13)23/h4-8H,1-3H3,(H,20,23)(H,21,22)
• InChI key: VNDWQCSOSCCWIP-UHFFFAOYSA-N

Description

General description

A potent, cell-permeable, reversible, and ATP-competitive inhibitor of Janus protein tyrosine kinases (JAKs). Displays potent inhibitory activity against JAK1 (IC₅₀ = 15 nM for murine JAK1), JAK2 (IC₅₀ = 1 nM), JAK3 (K_i = 5 nM), and Tyk2 (IC₅₀ = 1 nM). Inhibits other kinases at much higher concentrations. Shown to inhibit IL2- and IL4-dependent proliferation of CTLL cells and block the phosphorylation of STAT5, and further induce growth inhibition of multiple myeloma cells expressing activated JAKs and STAT3, unlike AG 490 (Cat. No. 658401).

A potent, reversible, cell-permeable, and ATP-competitive inhibitor of Janus protein tyrosine kinases (JAKs). Displays potent inhibitory activity against JAK1 (IC₅₀ = 15 nM for murine JAK1), JAK2 (IC₅₀ = 1 nM), JAK3 (K_i = 5 nM), and Tyk2 (IC₅₀ = 1 nM). Inhibits other kinases at much higher concentrations. Shown to inhibit IL2- and IL4-dependent proliferation of CTLL cells and block the phosphorylation of STAT5; and further induce growth inhibition of multiple myeloma cells expressing activated JAKs and STAT3, unlike AG 490 (Cat. No. 658401). A 10 mM (500 µg/162 µl) solution of JAK Inhibitor I (Cat. No. 420097) in DMSO is also available.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
murine JAK1

Product competes with ATP.

Reversible: yes

Target IC₅₀: 15 nM against murine JAK1; 1 nM against JAK2; 1 nM against Tyk2

Target K_i: 5 nM against JAK3

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Pedranzini, L., et al. 2006. Cancer Res.66, 9714.
Lucet, I.S., et al. 2005. Blood107, 176.
Thompson, J.E., et al. 2002. Bioorg. Med. Chem. Lett.12, 1219.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable