Home JAK/STAT JAK inhibitor S-Ruxolitinib (INCB018424)

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S-Ruxolitinib (INCB018424) JAK inhibitor

Cat.No.S2902

S-Ruxolitinib (INCB018424) is the first potent, selective JAK1/2 inhibitor to enter the clinic, with IC50 of 3.3 nM/2.8 nM and >130-fold selectivity for JAK1/2 versus JAK3. This compound is the chirality of INCB018424. Phase 3.
S-Ruxolitinib (INCB018424) JAK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 306.37

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Quality Control

Batch: Purity: 99.81%
99.81

Solubility

In vitro
Batch:

DMSO : 61 mg/mL (199.1 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 61 mg/mL

Water : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 306.37 Formula

C17H18N6

 Storage (From the date of receipt)
CAS No. 941685-37-6 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3

Mechanism of Action

Targets/IC50/Ki
JAK2
(Cell-free assay)
2.8 nM
JAK1
(Cell-free assay)
3.3 nM
TYK2
(Cell-free assay)
19 nM
In vitro
S-Ruxolitinib (INCB018424) potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. It markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. This compound (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. It 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.
Kinase Assay
Binding assay
Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with S-Ruxolitinib (INCB018424) or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC50) is calculated as the concentration of this compound required for inhibition of 50% of the fluorescent signal.
In vivo
S2902 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. S2902(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 S2902 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 S2902 (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 S2902 but has increased by 4% with the best available therapy at week 48. Patients in the S2902 group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis.
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06310304 Active not recruiting
Healthy Participants
Incyte Corporation
 March 26 2024 Phase 1
NCT02596347 Completed
Chronic Beryllium Disease (CBD)|Beryllium Sensitization (BeS)
National Jewish Health
 April 2015 --
NCT00617994 Completed
Psoriasis
Incyte Corporation
 August 31 2007 Phase 2

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