Ruxolitinib

Cas：941678-49-5 (free base)

Product Information：

Ruxolitinib, also known as INC424 and INCB18424 or INCB018424, is an orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.

Chemical Formula: C17H18N6

Exact Mass: 306.15929

Molecular Weight: 306.37

Elemental Analysis: C, 66.65; H, 5.92; N, 27.43

Synonym:

INCB01842

INCB 018424

INCB-018424

INC424

INC424

INC-424

INCB18424

INCB 18424

INCB-18424

trade name:J akafi and Jakavi

Chemical Name: (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile

InChi Key:

HFNKQEVNSGCOJV-OAHLLOKOSA-N

InChi Code: InChI=1S/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/m1/s1

Smiles Code:

N#CC[C@@H](N1N=CC(C2=C3C(NC=C3)=NC=N2)=C1)C4CCCC4

Technical Data：

Appearance: White to light yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro：

Ruxolitinib potently and selectively inhibits JAK2V617F-mediated signaling and proliferation, markedly increases apoptosis in a dose dependent manner, and at 64 nM results in a doubling of cells with depolarized mitochondria in Ba/F3 cells.

Ruxolitinib demonstrates remarkable potency against erythroid colony formation with IC50 of 67 nM, and inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 values of 407 nM and 223 nM, respectively.

In Vivo：

Ruxolitinib (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 and 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.

In the Ruxolitinib group, the primary end point is reached in 41.9% of patients, 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.

References：

1. Santos FP, Verstovsek S. Efficacy of ruxolitinib for myelofibrosis. Expert Opin Pharmacother. 2014 Jul;15(10):1465-73. doi: 10.1517/14656566.2014.923404. Epub 2014 May 24. Review. PubMed PMID: 24856675.

2. Molica M, Serrao A, Saracino R, Zacheo I, Stingone C, Alimena G, Breccia M. Disappearance of fibrosis in secondary myelofibrosis after ruxolitinib treatment: new endpoint to achieve? Ann Hematol. 2014 Nov;93(11):1951-2. doi: 10.1007/s00277-014-2096-y. Epub 2014 May 7. Review. PubMed PMID: 24801017.

3. Becker H, Engelhardt M, von Bubnoff N, Wäsch R. Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16. Review. PubMed PMID: 24756798.

4. Swaim SJ. Ruxolitinib for the treatment of primary myelofibrosis. Am J Health Syst Pharm. 2014 Mar 15;71(6):453-62. doi: 10.2146/ajhp120602. Review. PubMed PMID: 24589536.

5. Mesa RA, Cortes J. Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. J Hematol Oncol. 2013 Oct 22;6:79. doi: 10.1186/1756-8722-6-79. Review. PubMed PMID: 24283870; PubMed Central PMCID: PMC4222119.

Products are for research use only. Not for human use.