Home > Products > Apoptosis > JAK > Ruxolitinib

Ruxolitinib

(CAS No:941678-49-5)

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3.

CAS No:941678-49-5

Molecular Weight(MW):306.37

Purity:99.00%

Specification:500MG;1G;5G;10G;50G;100G

Price and large packaging, please e-mail consultation:info@SuperLan-chem.com

QC Documents

COA	MSDS	HPLC	NMR

ChemicalInfomation

CAS No:	941678-49-5
Molecular formula(MF)	C₁₇H₁₈N₆
Molecular Weight(MW):	306.37
Alias

Solubility

In vitro	DMSO	61 mg/mL (199.1 mM)
	Water	<1 mg/mL
	Ethanol	<1 mg/mL
In vivo	2% DMSO+30% PEG 300+ddH2O	5mg/mL

Biological Activity

Description

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3.

Targets

JAK2 ^[1] (Cell-free assay)	JAK1 ^[1] (Cell-free assay)
2.8 nM	3.3 nM

In vitro

INCB018424 potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. INCB018424 markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. INCB018424 (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. INCB018424 inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. INCB018424 demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM. ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
TF1	Kinase Assay		20 min	DMSO	Inhibition of JAK2 in human TF1 cells assessed as inhibition of EPO-induced STAT5 phosphorylation with IC50 of 0.012Î¼M	22698084
TF1	Kinase Assay		20 min	DMSO	Inhibition of JAK1 in human TF1 cells assessed as inhibition of IL6-induced STAT3 phosphorylation with IC50 of 0.024Î¼M	22698084
Human T cell	Kinase Assay				Inhibition of JAK3/1 in human T cells expressing CD3 assessed as inhibition of IL2-stimulated STAT5a phosphorylation with IC50 of 0.023Î¼M	23540648
Human monocyte	Kinase Assay				Inhibition of JAK2 in human monocytes expressing CD14 assessed as inhibition of GM-CSF-stimulated STAT5a phosphorylation with IC50 of 0.026Î¼M	23540648
Human monocyte	Kinase Assay				Inhibition of JAK2/1 in human monocytes expressing CD14 assessed as inhibition of IFNgamma-stimulated STAT1 phosphorylation with IC50 of 0.031Î¼M	23540648
HEL	Cytotoxic Assay	5 Î¼M	48 h		Cytotoxic index=12.2%	25931349
SET-2	Cytotoxic Assay	5 Î¼M	48 h		Cytotoxic index=18.7%	25931349
HT93A	Growth Inhibition Assay	320 nM	5 d	DMSO	Inhibition of GCS-F induced granulocytic differentiation	25805962
CMK	Growth Inhibition Assay				Inhibition of CMK carrying the JAK3A572V mutation cell proliferation	25352124
CMK	Growth Inhibition Assay				Inhibition of CMK carrying the JAK3A63D mutation cell proliferation with IC50 of 0.163 Î¼M	25352124
CMK	Growth Inhibition Assay				Inhibition of CMK carrying the WT JAK cell proliferation with IC50 of 0.075 Î¼M	25352124
NCI-H460	Growth Inhibition Assay			DMSO	IC50=0.13 Î¼M	25213670
NCI-H358	Growth Inhibition Assay			DMSO	IC50=0.1 Î¼M	25213670
A549	Growth Inhibition Assay			DMSO	IC50=0.04 Î¼M	25213670
A549/DDP	Growth Inhibition Assay			DMSO	IC50=0.22 Î¼M	25213670
NCI-H1299	Growth Inhibition Assay			DMSO	IC50=0.28 Î¼M	25213670
NCI-H2347	Growth Inhibition Assay			DMSO	IC50=0.17 Î¼M	25213670
A549/DDP	Function Assay	30 nM	48 h	DMSO	Down-regulation of STAT3 phosphorylation	25213670
NCI-H1299	Function Assay	30 nM	48 h	DMSO	Down-regulation of STAT3 phosphorylation	25213670
NCI-H2347	Function Assay	30 nM	48 h	DMSO	Decrease in Bcl2 expression	25213670
A549/DDP	Apoptosis Assay	30 nM	48 h	DMSO	Induction of apoptosis	25213670
NCI-H1299	Apoptosis Assay	30 nM	48 h	DMSO	Induction of apoptosis	25213670
NCI-H2347	Apoptosis Assay	30 nM	48 h	DMSO	Induction of apoptosis	25213670
Hep3B	Function Assay	1 Î¼M	16 h	DMSO	Impaires the capacity of IHCA-associated gp130 mutants to active STAT3 with IC50 of ~50 Î¼M	24501689
HepG2	Function Assay	1 Î¼M	16 h	DMSO	Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3	24501689
Huh7	Function Assay	1 Î¼M	16 h	DMSO	Impaires the capacity of IHCA-associated gp130 mutants to signal to STAT3	24501689
BaF3	Kinase Assay	80 nM	6 h	DMSO	Reduces the phosphorylation ofÂ STAT5 in JAK2V617F-mutated BAF3-EPOR cell	24237791
DLD-1	Kinase Assay	25 Î¼M	48 h	DMSO	Inhibition of JAK1 phosphorylation	24050550
RKO	Kinase Assay	25 Î¼M	48 h	DMSO	Inhibition of JAK1 phosphorylation	24050550
DLD-1	Kinase Assay	25 Î¼M	48 h	DMSO	Inhibition of JAK2 phosphorylation	24050550
RKO	Kinase Assay	25 Î¼M	48 h	DMSO	does not inhibit JAK1 phosphorylation	24050550
DLD-1	Growth Inhibition Assay	50 Î¼M	48 h	DMSO	IC50=15.51 Î¼M	24050550
RKO	Growth Inhibition Assay	50 Î¼M	48 h	DMSO	IC50=14.76 Î¼M	24050550
DLD-1	Apoptosis Assay	25 Î¼M	48 h	DMSO	Induces apoptosis by activating caspase 3	24050550
RKO	Apoptosis Assay	25 Î¼M	48 h	DMSO	Induces apoptosis by activating caspase 3	24050550
HuH7	Growth Inhibition Assay	50 Î¼M	48 h	DMSO	>82% reduction	23941832
SNU182	Growth Inhibition Assay	50 Î¼M	48 h	DMSO	>64% reduction	23941832
SNU423	Growth Inhibition Assay	50 Î¼M	48 h	DMSO	>81% reduction	23941832
HuH7	Function Assay	50 Î¼M	24 h	DMSO	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832
SNU182	Function Assay	50 Î¼M	24 h	DMSO	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832
SNU423	Function Assay	50 Î¼M	24 h	DMSO	Inhibition of STAT1 and STAT3 phosphorylation significantly	23941832

... Click to View More Cell Line Experimental Data

In vivo

INCB018424 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. INCB018424 (180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. ^[1] The primary end point is reached in 41.9% of patients in the Ruxolitinib group as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score. ^[2] A total of 28% of the patients in the Ruxolitinib (15 mg twice daily) group has at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with Ruxolitinib but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. ^[3]