[CAS NO. 941685-37-6] S-Ruxolitinib (INCB018424)

Name: S-Ruxolitinib (INCB018424)
Brand: Arctom Scientific
SKU: SLK-S2902

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PRODUCTS SPECIFICATIONS [941685-37-6]

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Catalog

SLK-S2902

Brand

Selleck

CAS

941685-37-6

DESCRIPTION [941685-37-6]

Overview

MDL	MFCD13184797
Molecular Weight	306.37
Molecular Formula	C17H18N6
SMILES	[C@@H](CC#N)(N1C=C(C2=C3C(=NC=N2)NC=C3)C=N1)C4CCCC4

For research use only.

Storage

3 years,-20°C,powder
1 years,-80°C,in solvent

Shipping

Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Concentration Volume Mass	1 mg	5 mg	10 mg
1 mM	3.2640 mL	16.3201 mL	32.6403 mL
5 mM	0.6528 mL	3.2640 mL	6.5281 mL
10 mM	0.3264 mL	1.6320 mL	3.2640 mL
50 mM	0.0653 mL	0.3264 mL	0.6528 mL

Description

S-Ruxolitinib is the chirality of INCB018424, which is the first potent, selective, inhibitor to enter the clinic with of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3.

Targets

JAK2 ^[1] (Cell-free assay)	JAK1 ^[1] (Cell-free assay)	TYK2 ^[1] (Cell-free assay)
2.8 nM	3.3 nM	19 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.

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. 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. 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.

References

[1] Quintas-Cardama A, et al. Blood, 2010, 115(15), 3109-3117.
[2] Verstovsek S, et al. N Engl J Med, 2012, 366(9), 799-807.
[3] Harrison C, et al. N Engl J Med, 2012, 366(9), 787-798.

Synonyms

1H-Pyrazole-1-propanenitrile, β-cyclopentyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-, (βS)-

(βS)-β-Cyclopentyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazole-1-propanenitrile

INCB 18424

(3S)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

S-Ruxolitinib

(3S)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile