JAK3-IN-2

Research use only, not for human use.

A potent and highly selective JAK3 inhibitor with IC50 of 0.15 nM.

A potent and highly selective JAK3 inhibitor with IC50 of 0.15 nM; dispalys >4,300-fold selectivity over JAK1, JAK2 and TYK2, and other kinases BMX, EGFR, ITK and BTK; blocks cytokine signaling through JAK3, but not through other JAK family enzymes; inhibits IL-7 induced pSTAT5 in CD3+, CD8+ T cells with IC50 of 280 nM; sufficiently blocks the development of inflammation in a rat model of rheumatoid arthritis, while sparing hematopoiesis.

JAK3-IN-6 (compound 2), a potent inhibitor of JAK3 (0.15 nM) is 4300-fold selective for JAK3 over JAK1 in enzyme assays, 67-fold (IL-2 vs. IL-6) or 140-fold (IL-2 vs. EPO or GMCSF) selective in cellular reporter assays and >35-fold selective in human PBMC assays (IL-7 vs. IL-6 or GMCSF). Irreversible JAK3-IN-6 with a JAK1 selective inhibitor 3 (JAK1: 0.96 nM, JAK2: 14 nM, JAK3: >1500 nM, TYK2: 10 nM) are cross titrated to determine if there is an additive or synergistic effect of co-inhibiting JAK1 and JAK3 enzymes on IL-7 signaling in CD3+, CD4+ PBMCs. As shown, the predicted levels of pSTAT5 inhibition based on addition of JAK1 and JAK3 inhibition are very close to the measured effects of cross titrating each compound, demonstrating that there is an additive effect but no synergistic effect of inhibiting JAK1 and JAK3 on blocking STAT5 phosphorylation. Furthermore inhibition of either JAK1 or JAK3 alone is sufficient to fully inhibit pSTAT5.

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JAK3 inhibitor 2

Angiogenesis

JAK

JAK

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1443235-95-7

350.378

C19H18N4O3

>98% (HPLC)

In Vitro:?DMSO : 260 mg/mL (742.07 mM)

O=C(C1=CNC2=NC=NC(C3=CC=CC(NC(C(C)=C)=O)=C3)=C21)OCC

ethyl 4-(3-methacrylamidophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

(-20℃)

With Ice Pack

≥ 2 years