ruxolitinib   Click here for help

GtoPdb Ligand ID: 5688

Synonyms: (R)-ruxolitinib | INC424 | INCB 18424 | INCB018424 | Jakafi® | Jakavi®
Approved drug PDB Ligand Immunopharmacology Ligand
ruxolitinib is an approved drug (FDA (2011), EMA (2012))
Compound class: Synthetic organic
Comment: Ruxolitinib is a Type-1 kinase inhibitor and was first approved by the US FDA in 2011. Ruxolitinib has high potency against Janus kinases 1 and 2 (JAK1, JAK2), as well as against the related family member, tyrosine kinase 2 (TYK2) [3]. Inhibitory activity against JAK3 is only slightly reduced compared to the other three family kinases.
Marketed formulations may contain ruxolitinib phosphate (PubChem CID 25127112).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 83.18
Molecular weight 306.16
XLogP 2.7
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES N#CCC(n1ncc(c1)c1ncnc2c1cc[nH]2)C1CCCC1
Isomeric SMILES N#CC[C@@H](n1ncc(c1)c1ncnc2c1cc[nH]2)C1CCCC1
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
InChI Key HFNKQEVNSGCOJV-OAHLLOKOSA-N
References
1. Clark JD, Flanagan ME, Telliez JB. (2014)
Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.
J Med Chem, 57 (12): 5023-38. [PMID:24417533]
2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
3. Hanan EJ, van Abbema A, Barrett K, Blair WS, Blaney J, Chang C, Eigenbrot C, Flynn S, Gibbons P, Hurley CA et al.. (2012)
Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.
J Med Chem, 55 (22): 10090-107. [PMID:23061660]
4. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. (2016)
Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata.
JCI Insight, 1 (15): e89790. [PMID:27699253]
5. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P et al.. (2010)
Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.
Blood, 115 (15): 3109-17. [PMID:20130243]
6. Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB, Butler K, Kuo F, Sun K, Ji T et al.. (2020)
Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial.
Lancet, 396 (10244): 110-120. [PMID:32653055]
7. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]
8. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L et al.. (2014)
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Nat Med, 20 (9): 1043-9. [PMID:25129481]