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Product Details:

  • CAS No: 1092939-17-7
  • AHFC code: 10:00
  • Synonyms: 3R)-3-Cyclopentyl-3-(4-(7H-pyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile phosphate (1:1), INCB018424 salt, Jakafi, Jakavi, Ruxolitinib phosphate, UNII-436LRU32H5
  • ATC Code: L01XE18
  • Chemical Formula: C17-H18-N6.H3-O4-P
  • Molecular Weight: 404.3649
  • Assay/Purity: Typically NLT 98%
  • DrugBank: DB08877
  • SMILES: C(#N)C[C,H]([C,,H]1CCCC1)n1ncc(c1)c1ncnc2c1cc[nH]2.P(=O)(O)(O)O
  • InChl: 1S/C17H18N6.H3O4P/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;1-5(2,3)4/h6,8-12,15H,1-5H2,(H,19,20,21);(H3,1,2,3,4)/t15-;/m1./s1
  • PubChem:
  • IUPAC: 1H-Pyrazole-1-propanenitrile, beta-cyclopentyl-4-(7H-pyrrolo(2,3-d)pyrimidin-4-yl)-,(betaR)-, phosphate (1:1)

Additional Details

Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. [Lexicomp] Myeolofibrosis is the proliferation of abnormal bone marrow stem cells which cause fibrosis (the excessive formation of connective tissue).
The mean half-maximal inhibitory concentration (IC50) for JAK 1 and JAK 2 are 2.8 nmol/L and 3.3 nmol/L respectively. After administration of ruxolitinib, a decrease in levels of phosphorylated STAT (marker for JAK activity) in a dose-dependent manner can be observed. Pharmacodynamic resistance has not been observed.
Mode of Action:
Ruxolitinib is a kinase inhibitor that is selective for the Janus Associated Kinases (JAK) 1 and 2. These kinases are responsible for the mediation of cytokine and growth factor signalling which in turn effect immune function and hematopoiesis. The signalling process involves signal transducers and transcription activators (STAT) which modulate gene expression. Patients with myelofibrosis have abnormal JAK1 and JAK2 activity thus ruxolitinib works to regulate this.
Ruxolitinib is metabolized by CYP3A4. Less potent active metabolites forms as a result.
Thrombocytopenia was the dose-limiting toxicity.
General Reference:
Cervantes F, Martinez-Trillos A: Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013 May;14(7):873-84. doi: 10.1517/14656566.2013.783019. Epub 2013 Mar 21. PubmedLexi-Comp, Inc. (Lexi-DrugsTM ). Lexi-Comp, Inc.; July, 2013.Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. Pubmed
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