JAK3-IN-1

Research use only, not for human use.

JAK3-IN-1 is a potent and selective JAK3 inhibitor with IC50 of 4.8 nM.

JAK3-IN-1 is a potent and selective JAK3 inhibitor with IC50 of 4.8 nM; displays >150 fold selectivity versus JAK1 and JAK2; exhibits decent pharmacokinetic properties and is suitable for use in vivo.

JAK3-IN-1(Compound 9; 0-5 μM; 3 hours; BMDMs cells) treatment completely inhibits IL-4 induced p-STAT6 at a concentration of 500 nM and only partially inhibits IFNβ-induced p-STAT1 at a concentration of 5.0 μM.JAK3-IN-1(Compound 9) most potently inhibits JAK3 and identified fms-related tyrosine kinase 3 (FLT3) and several tyrosine protein kinase (TEC)-family kinases as being potential off-targets. Enzymatic assays using the Z’-lyte or LanthaScreen formats confirmed enzymatic inhibition of FLT3 (IC50 = 13 nM), TTK protein kinase (TTK, IC50 = 49 nM), BLK proto-oncogene (BLK, IC50 = 157 nM) and tyrosine protein kinase TXK (TXK, IC50 = 36 nM). JAK3-IN-1 shows very low inhibition scores for other JAKs and wild-type (WT) EGFR, which is consistent with the over 180-fold higher IC50s against EGFRWT andTYK2 (IC50s =409 nM,> 10000 respectively). JAK3-IN-1 possesses over 165-fold higher IC50s for BTK or ITK (IC50s = 794 and 1070 nM respectively).JAK3-IN-1(Compound 9) selectively inhibits the proliferation of JAK3-dependent Ba/F3 cells (IC50 = 69 nM) relative to other JAK-dependent Ba/F3 cells, for which there was no antiproliferative effect at concentrations below 3.0 μM. TWestern Blot Analysis Cell Line:BMDMs cells Concentration:0 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM Incubation Time:3 hours Result:Completely inhibited IL-4 induced p-STAT6 at a concentration of 500 nM and only partially inhibited IFNβ-induced p-STAT1 at a concentration of 5.0 μM.

JAK3-IN-1(Compound 9) shows reasonable pharmacokinetic properties, with moderate T1/2 of 1.4 h, area under the curve (AUC) value of 795 ng*hr/mL following a 10 mg/Kg oral dose and good oral bioavailability of 66%. After oral administration with JAK3-IN-1(Compound 9) (75 mpk, QD) for 8 days, the numbers of B or T lymphocytes in the tumor-bearing lungs and spleens of treated mice is not affected, however, the number of NK cells is reduced.

JAK3-IN-1 | JAK3IN1 | JAK3 IN 1 | JAK3IN-1 | JAK3-IN1

Angiogenesis

JAK

JAK

Cancer

——

1805787-93-2

508.0151

C26H30ClN7O2

>98% (HPLC)

DMSO: ≥ 47 mg/mL

C=CC(NC1=CC=CC(CNC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3OC)=NC=C2Cl)=C1)=O

2-Propenamide, N-[3-[[[5-chloro-2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-4-pyrimidinyl]amino]methyl]phenyl]-

(-20℃)

With Ice Pack

≥ 2 years