JAK3 INHIBITOR VI

Product NameJAK3 INHIBITOR VI
CAS856436-16-3
MFC18H13N3O.CH4O3S
MW383.42
EINECS
MOL File856436-16-3.mol

Chemical Properties

storage temp.	+2C to +8C
solubility	water: 1 mg/mL \|\| DMSO: 5 mg/mL
form	Yellow solid
color	yellow
Water Solubility	water: 1mg/mL DMSO: 5mg/mL
InChI	1S/C18H13N3O.CH4O3S/c22-18-16(10-14-4-2-8-20-14)15-9-12(5-6-17(15)21-18)13-3-1-7-19-11-13;1-5(2,3)4/h1-11,20H,(H,21,22);1H3,(H,2,3,4)/b16-10-;
InChIKey	ZUDPNBZMAJGYTE-HYMQDMCPSA-N
SMILES	[S](=O)(=O)(O)C.[nH]1c(ccc1)\C=C2\c3c(ccc(c3)c4cnccc4)NC\2=O

Safety Information

WGK Germany	WGK 1
Storage Class	11 - Combustible Solids

Usage And Synthesis

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

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 (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

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