Ruxolitinib

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Ruxolitinib
Ruxolitinib2DACS.svg
Systematic (IUPAC) name
(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
Clinical data
Trade names Jakafi, Jakavi
AHFS/Drugs.com monograph
MedlinePlus a612006
Licence data EMA:Link, US FDA:link
Pregnancy cat. C (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral, topical
Pharmacokinetic data
Bioavailability 95%[1]
Protein binding 97%[1]
Metabolism Hepatic (mainly CYP3A4-mediated)[1]
Half-life 2.8-3 hours[1]
Excretion Urine (74%), faeces (22%)[1]
Identifiers
CAS number 941678-49-5 YesY
ATC code L01XE18
ChemSpider 25027389 YesY
UNII 82S8X8XX8H YesY
ChEMBL CHEMBL1789941 N
Synonyms INCB018424, INC424
Chemical data
Formula C17H18N6 
Mol. mass 306.37 g/mol
 N (what is this?)  (verify)

Ruxolitinib (INC424, INCB18424, trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of bone marrow cancer.[2][3] It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer),[4] for polycythemia vera,[4] and for plaque psoriasis.

The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size, relieving debilitating symptoms, and improving overall survival.[5][6][7][8]

Mechanism of action[edit]

Ruxolitinib is a Janus kinase inhibitor with selectivity for subtypes JAK1 and JAK2 of this enzyme.[9][10] Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.

Side effects[edit]

Immunologic side effects have included herpes zoster (shingles) (1.9%) and case reports of opportunistic infections.[11] Metabolic side effects have included weight gain (7.1%). Laboratory abnormalities have included alanine transaminase (ALT) abnormalities (25.2%), aspartate transaminase (AST) abnormalities (17.4%), and elevated cholesterol levels (16.8%).[citation needed]

Legal status[edit]

In November 2011, ruxolitinib was approved by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate or high-risk myelofibrosis based on results of the COMFORT-I and COMFORT-II Trials.[12]

Economics[edit]

Some analysts believe this to be a potential blockbuster drug.[4] As of the end of March 2012, and according to an Incyte spokesman, approximately 1000 physicians had prescribed the drug in the United States, out of a total 6500 hematologists and oncologists nationwide.[4]

References[edit]

  1. ^ a b c d e "Jakafi (ruxolitinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 16 February 2014. 
  2. ^ Mesa, Ruben A.; Yasothan, Uma; Kirkpatrick, Peter (2012). "Ruxolitinib". Nature Reviews Drug Discovery 11 (2): 103–4. doi:10.1038/nrd3652. PMID 22293561. 
  3. ^ Harrison, C; Mesa, R; Ross, D; Mead, A; Keohane, C; Gotlib, J; Verstovsek, S (2013). "Practical management of patients with myelofibrosis receiving ruxolitinib". Expert Review of Hematology 6 (5): 511–23. doi:10.1586/17474086.2013.827413. PMID 24083419. 
  4. ^ a b c d Natoli, Cori Anne (May 5, 2012), "Incyte looks to ride on drug's success", The News Journal, retrieved May 6, 2012 
  5. ^
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  8. ^ ASCO Annual Meeting 2011: JAK Inhibitor Ruxolitinib Demonstrates Significant Clinical Benefit in Myelofibrosis
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  11. ^ Wysham, NG; Allada G, Sullivan DR (2013). Chest 143 (5): 1478–9. PMID 23648912. 
  12. ^ "FDA Approves Incyte's Jakafi(TM) (ruxolitinib) for Patients with Myelofibrosis" (Press release). Incyte. Retrieved 2012-01-02.