JAK2-IN-7

• CAT Number: I045439
• CAS Number: 2593402-36-7
• Molecular Formula: C26H33N7O
• Molecular Weight: 459.59
• Purity: ≥95%
• Synonyms: (E)-4-(dimethylamino)-1-[6-[[5-methyl-4-(1-propan-2-ylpyrazol-4-yl)pyrimidin-2-yl]amino]-3,4-dihydro-1H-isoquinolin-2-yl]but-2-en-1-one
• InChI: InChI=1S/C26H33N7O/c1-18(2)33-17-22(15-28-33)25-19(3)14-27-26(30-25)29-23-9-8-21-16-32(12-10-20(21)13-23)24(34)7-6-11-31(4)5/h6-9,13-15,17-18H,10-12,16H2,1-5H3,(H,27,29,30)/b7-6+
• InChIKey: SURRDPSGERGIIM-VOTSOKGWSA-N
• SMILES: CC1=CN=C(N=C1C2=CN(N=C2)C(C)C)NC3=CC4=C(CN(CC4)C(=O)C=CCN(C)C)C=C3

JAK2-IN-7 is a selective JAK2 inhibitor with IC50s of 3, 11.7, and 41 nM for JAK2, SET-2, and Ba/F3V617F cells, respectively. JAK2-IN-7 possesses >14-fold selectivity over JAK1, JAK3, FLT3. JAK2-IN-7 stimulates cell cycle arrest in the G0/G1 phase and induces tumor cellapoptosis. Antitumor activities[1].
JAK2-IN-7 (compound 13ac) (0-1000 nM; 2 hours) inhibits JAK2 and STAT5 phosphorylation in a dose-dependent manner in SET-2 and Ba/F3-JAK2V617F cells[1].
JAK2-IN-7 (10-160 nM; 24 hours) induces cell arrest in the G0/G1 phase[1].
JAK2-IN-7 (0.05-1.6 μM; 2 hours) induces apoptosis in SET-2 cells[1].
JAK2-IN-7 (15-60 mg/kg; p.o.; daily for 16 days) shows potent in vivo antitumor efficacy with 82.3% tumor growth inhibition in the SET-2 xenograft model[1].
JAK2-IN-7 (30-60 mg/kg; p.o.; q.d. for 16 day) significantly ameliorates the disease symptoms in a Ba/F3-JAK2V617F allograft model, with 77.1% normalization of spleen weight, which was more potent than Ruxolitinib[1].

Reference

[1]. Yang T, et al. N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms [published online ahead of print, 2020 Nov 30]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01488.
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