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) (IC
50 = 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 (IC
50 = 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
JI6 (15 mg/kg; i.p. daily for 3 weeks) inhibits the proliferation of FLT3-D835Y-transformed HCD-57 in immunodeficient mice and prolongs the mice survival[1].
JI6 (25 mg/kg; p.o. daily for 3 weeks) suppresses myeloproliferative phenotypes in FLT3-ITD knock-in mice[1].
JI6 (100 mg/kg; a single i.p.) significantly inhibits phosphorylation of FLT3 and downstream signal transductionin mice expressing FLT3-D835Y[1].
| Animal Model: | NSG mice (10-12 weeks old, male) were implanted with FLT3-D835Y-transformed HCD-57 cells[1] |
| Dosage: | 15 mg/kg |
| Administration: | I.p. daily for 3 weeks |
| Result: | Reduced the spleen size and prolonged the survival of these mice.
|
IC 50
FLT3-D835H: 4 nM (IC
50); FLT3-D835Y: 8 nM (IC
50); FLT3-WT: 40 nM (IC
50); JAK3: ~250 nM (IC
50); c-Kit: ~500 nM (IC
50)
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
