JAK3 INHIBITOR VI

Uses

JI6 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ～40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits JAK3 and c-Kit, with IC50s of ～250 and ～500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia[1].

General Description

A cell-permeable, potent, and reversible inhibitor of Janus kinase 3 (JAK3) (IC₅₀ = 27 nM). Reported to bind to the enzyme active site and prevent IL-2-induced phosphorylation of JAK3 and STAT5. Also reported to inhibit IL-2-induced cell proliferation (IC₅₀ = 760 nM for murine CTLL cells and 250 nM for human T-cells). Shown to alleviate oxazolone-induced ear edema in mice with an efficacy comparable to Dexamethasone (Cat. No. 265005) and displays ~16-fold greater selectivity over JAK2.

Biochem/physiol Actions

Cell permeable: yes

in vivo

IC 50

FLT3-D835H: 4 nM (IC₅₀); FLT3-D835Y: 8 nM (IC₅₀); FLT3-WT: 40 nM (IC₅₀); JAK3: ~250 nM (IC₅₀); c-Kit: ~500 nM (IC₅₀)

References

[1] Chen Y, et, al. Identification of an orally available compound with potent and broad FLT3 inhibition activity. Oncogene. 2016 Jun 9;35(23):2971-8. DOI:10.1038/onc.2015.362