Jakafi

Ruxolitinib

Clinical data
Trade names	Jakafi, Jakavi
AHFS/Drugs.com	Monograph
MedlinePlus	a612006
License data	EU EMA: Jakavi US FDA: Ruxolitinib
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	By mouth, topical
ATC code	L01XE18 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	95%
Protein binding	97%
Metabolism	Hepatic (mainly CYP3A4-mediated)
Biological half-life	2.8-3 hours
Excretion	Urine (74%), faeces (22%)
Identifiers
IUPAC name (3R)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
Synonyms	INCB018424, INC424
CAS Number	941678-49-5 Y
PubChem CID	25126798
IUPHAR/BPS	5688
ChemSpider	25027389 Y
UNII	82S8X8XX8H
KEGG	D09959 N
ChEMBL	CHEMBL1789941 N
PDB ligand	RXT (PDBe, RCSB PDB)
Chemical and physical data
Formula	C17H18N6
Molar mass	306.37 g/mol
3D model (Jmol)	Interactive image
SMILES C1CCC(C1)C(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3
InChI 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 Y Key:HFNKQEVNSGCOJV-OAHLLOKOSA-N Y
NY (what is this?)

Ruxolitinib (trade names Jakafi JAK-ə-fye and Jakavi) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow, and for polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea.

Ruxolitinib is a janus kinase inhibitor with selectivity for subtypes JAK1 and JAK2 of this enzyme. 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 include thrombocytopenia (low blood platelet count), anemia (low red blood cell count) and neutropenia; risk of infection; symptom exacerbation if the medication is interrupted or discontinued; and non-melanoma skin cancer.

Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels.

The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size and relieving debilitating symptoms.