Ruxolitinib
Identification
- Summary
Ruxolitinib is a kinase inhibitor used to treat various types of myelofibrosis, polycythemia vera in patients who have not responded to or cannot tolerate hydroxyurea, and to treat graft-versus-host disease in cases that are refractory to steroid treatment.
- Brand Names
- Jakafi, Jakavi, Opzelura
- Generic Name
- Ruxolitinib
- DrugBank Accession Number
- DB08877
- Background
Ruxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2,3 which are tyrosine kinases involved in cytokine signalling and hematopoiesis.2 Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation.5 Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed.15
Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012.5 In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of hydroxyurea and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children.19 The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo.23 It is being investigated for other inflammatory skin conditions.12
Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia.6,7 However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications 20 thus the drug was not approved as a treatment for COVID-19.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 306.365
Monoisotopic: 306.159294606 - Chemical Formula
- C17H18N6
- Synonyms
- Ruxolitinib
- External IDs
- INC-424
- INC424
- INCB 18424
- INCB-018424
- INCB-18424
- INCB018424
- INCB18424
- INCB424
Pharmacology
- Indication
Ruxolitinib is indicated for the treatment of the following conditions:
- intermediate or high-risk myelofibrosis (MF), including prima1y MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.16 It is also used to treat disease-related splenomegaly or symptoms in adult patients with these conditions.22
- polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.16
- steroid-refracto1y acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.16
- chronic GVHD in patients aged 12 years and older who have failed one or two lines of systemic therapy.16
Topical ruxolitinib is indicated for:
- the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.23
- the treatment of non-segmental vitiligo in adult and pediatric patients 12 years of age and older.23,24
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Acute graft-versus-host disease •••••••••••• •••••• ••••••••• ••••••• •••••••••• •••••• Management of Chronic graft-versus-host disease •••••••••••• •••••• ••••••••• ••••••• •• •• ••••• ••• ••••• •••••••• ••••••• •••••• Management of Nonsegmental vitiligo •••••••••••• ••••••••••• ••••• ••••• Management of Post-essential thrombocythemia myelofibrosis •••••••••••• ••••• •••••• Management of Post-polycythemia vera myelofibrosis •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT).4 Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity, 2 by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera.16 In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis.4 In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival.2 Ruxolitinib inhibits both mutant and wild-type JAK2 4; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor treatment.14
- Mechanism of action
The Janus kinase (JAK) family of protein tyrosine kinases comprises JAK1, JAK2, JAK3, and non-receptor tyrosine kinase 2 (TYK2).4 JAKs play a pivotal role in intracellular signalling pathways of various cytokines and growth factors essential to hematopoiesis, such as interleukin, erythropoietin, and thrombopoietin.2 JAKs have diverse functions: JAK1 and JAK3 promote lymphocyte differentiation, survival, and function, while JAK2 promotes signal transduction of erythropoietin and thrombopoietin.4,10 JAKs are in close proximity to the cytokine and growth factor receptor’s cytoplasmic region. Upon binding of cytokines and growth factors, JAKs are activated, undergoing cross-phosphorylation and tyrosine phosphorylation. This process also reveals selective binding sites for STATs, which are DNA-binding proteins that also bind to the cytoplasmic region of cytokine or growth factor receptors. Activated JAKs and STATs translocate to the nucleus as transcription factors to regulate gene expression of pro-inflammatory cytokines such as IL-6, IL-10, and nuclear factor κB (NF-κB).15 They also activate downstream pathways that promote erythroid, myeloid, and megakaryocytic development.4
The molecular pathogenesis of myeloproliferative neoplasms is not fully understood; however, JAK2 is constitutively activated and the JAK-STAT signalling pathway becomes deregulated and aberrant.2,15 Ruxolitinib is a selective and potent inhibitor of JAK2 and JAK1, with some affinity against JAK3 and TYK2. Anticancer effects of ruxolitinib are attributed to its inhibition of JAKs and JAK-mediated phosphorylation of STAT3.16 By downregulating the JAK-STAT pathway, ruxolitinib inhibits myeloproliferation and suppresses the plasma levels of pro-inflammatory cytokines such as IL-6 and TNF-α.4
Activated JAKs are also implicated in graft-versus-host-disease (GVHD), which is a severe immune complication of allogeneic hematopoietic cell transplantation GVHD is associated with significant morbidity and mortality, especially for patients who do not respond well to corticosteroid therapy. Activated JAKS stimulate T-effector cell responses, leading to increased proliferation of effector T cells and heightened production of pro-inflammatory cytokines. By blocking JAK1 and JAk2, ruxolitinib inhibits donor T-cell expansion and suppresses pro-inflammatory responses.13
Target Actions Organism ATyrosine-protein kinase JAK2 inhibitorHumans ATyrosine-protein kinase JAK1 inhibitorHumans ATyrosine-protein kinase JAK3 inhibitorHumans ANon-receptor tyrosine-protein kinase TYK2 inhibitorHumans - Absorption
Following oral administration, ruxolitinib undergoes rapid absorption 10 and the peak concentrations are reached within one hour after administration.4 Over a single-dose range of 5 mg to 200 mg, the mean maximal plasma concentration (Cmax) increases proportionally. Cmax ranged from 205 nM to 7100 nM and AUC ranged from 862 nM x hr to 30700 nM x hr. Tmax ranges from one to two hours following oral administration. Oral bioavailability is at least 95%.16
- Volume of distribution
The mean volume of distribution (%coefficient of variation) at steady-state is 72 L (29%) in patients with myelofibrosis and 75 L (23%) in patients with polycythemia vera.16 It is not known whether ruxolitinib crosses the blood-brain barrier.21
- Protein binding
Ruxolitinib is approximately 97% bound to plasma proteins, mostly to albumin.16
- Metabolism
More than 99% of orally-administered ruxolitinib undergoes metabolism4 mediated by CYP3A4 and, to a lesser extent, CYP2C9.16 The major circulating metabolites in human plasma were M18 formed by 2-hydroxylation, and M16 and M27 (stereoisomers) formed by 3-hydroxylation. Other identified metabolites include M9 and M49, which are formed by hydroxylation and ketone formation. Not all metabolite structures are fully characterized and it is speculated that many metabolites exist in stereoisomers.10 Metabolites of ruxolitinib retain inhibitory activity against JAK1 and JAk2 to a lesser degree than the parent drug.11
Hover over products below to view reaction partners
- Route of elimination
Following oral administration of a single radiolabeled dose of ruxolitinib, the drug was mainly eliminated through metabolism. About 74% of the total dose was excreted in urine and 22% was excreted in feces,16 mostly in the form of hydroxyl and oxo metabolites of ruxolitinib.10 The unchanged parent drug accounted for less than 1% of the excreted total radioactivity.16
- Half-life
The mean elimination half-life of ruxolitinib is approximately 3 hours and the mean half-life of its metabolites is approximately 5.8 hours.16
- Clearance
Ruxolitinib clearance (% coefficient of variation) is 17.7 L/h in women and 22.1 L/h in men with myelofibrosis. Drug clearance was 12.7 L/h (42%) in patients with polycythemia vera and 11.9 L/h (43%) in patients with acute graft-versus-host disease.16
- Adverse Effects
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- Toxicity
The oral LD50 was 250 mg/kg.18
Single doses of ruxolitinib up to 200 mg were tolerated well. Higher doses than recommended repeat doses are associated with myelosuppression, including leukopenia, anemia, and thrombocytopenia. There is no known antidote for overdoses with ruxolitinib: it is recommended that patients are given appropriate supportive treatment. Hemodialysis is not expected to enhance the elimination of ruxolitinib.16
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Ruxolitinib which could result in a higher serum level. Abametapir The serum concentration of Ruxolitinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Ruxolitinib can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Ruxolitinib. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Ruxolitinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of ruxolitinib.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum levels of ruxolitinib.
- Take with or without food. A high-fat, high-calorie meal had negligible effects on the pharmacokinetics of ruxolitinib.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Recilisib sodium 1068SXU525 922139-31-9 PRFBWBYKWZVQJF-RRABGKBLSA-M Ruxolitinib phosphate 436LRU32H5 1092939-17-7 JFMWPOCYMYGEDM-XFULWGLBSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Jakafi Tablet 5.0 mg/1 Oral Incyte Corporation 2011-11-16 Not applicable US Jakafi Tablet 15.0 mg/1 Oral Incyte Corporation 2011-11-16 Not applicable US Jakafi Tablet 25.0 mg/1 Oral Incyte Corporation 2011-11-16 Not applicable US Jakafi Tablet 10.0 mg/1 Oral Incyte Corporation 2011-11-16 Not applicable US Jakafi Tablet 20.0 mg/1 Oral Incyte Corporation 2011-11-16 Not applicable US
Categories
- ATC Codes
- D11AH09 — Ruxolitinib
- D11AH — Agents for dermatitis, excluding corticosteroids
- D11A — OTHER DERMATOLOGICAL PREPARATIONS
- D11 — OTHER DERMATOLOGICAL PREPARATIONS
- D — DERMATOLOGICALS
- Drug Categories
- Agents for Dermatitis, Excluding Corticosteroids
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cancer immunotherapy
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Dermatologicals
- Drugs that are Mainly Renally Excreted
- Immunosuppressive Agents
- Immunotherapy
- Janus Kinase Inhibitor
- Janus Kinases, antagonists & inhibitors
- Kinase Inhibitor
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrrolo[2,3-d]pyrimidines. These are aromatic heteropolycyclic compounds containing a pyrrolo[2,3-d]pyrimidine ring system, which is an pyrrolopyrimidine isomers having the 3 ring nitrogen atoms at the 1-, 5-, and 7-positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrrolopyrimidines
- Sub Class
- Pyrrolo[2,3-d]pyrimidines
- Direct Parent
- Pyrrolo[2,3-d]pyrimidines
- Alternative Parents
- Pyrimidines and pyrimidine derivatives / Pyrroles / Pyrazoles / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Azole / Carbonitrile / Heteroaromatic compound / Hydrocarbon derivative / Nitrile / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- pyrazoles, nitrile, pyrrolopyrimidine (CHEBI:66919)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 82S8X8XX8H
- CAS number
- 941678-49-5
- InChI Key
- HFNKQEVNSGCOJV-OAHLLOKOSA-N
- 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
- IUPAC Name
- (3R)-3-cyclopentyl-3-(4-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}-1H-pyrazol-1-yl)propanenitrile
- SMILES
- N#CC[C@H](C1CCCC1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1
References
- General References
- 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. [Article]
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
- Becker H, Engelhardt M, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16. [Article]
- Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81. [Article]
- Ajayi S, Becker H, Reinhardt H, Engelhardt M, Zeiser R, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2018;212:119-132. doi: 10.1007/978-3-319-91439-8_6. [Article]
- Cao Y, Wei J, Zou L, Jiang T, Wang G, Chen L, Huang L, Meng F, Huang L, Wang N, Zhou X, Luo H, Mao Z, Chen X, Xie J, Liu J, Cheng H, Zhao J, Huang G, Wang W, Zhou J: Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol. 2020 Jul;146(1):137-146.e3. doi: 10.1016/j.jaci.2020.05.019. Epub 2020 May 26. [Article]
- La Rosee F, Bremer HC, Gehrke I, Kehr A, Hochhaus A, Birndt S, Fellhauer M, Henkes M, Kumle B, Russo SG, La Rosee P: The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020 Jul;34(7):1805-1815. doi: 10.1038/s41375-020-0891-0. Epub 2020 Jun 9. [Article]
- Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB, Butler K, Kuo F, Sun K, Ji T, Howell MD, Harris JE: Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020 Jul 11;396(10244):110-120. doi: 10.1016/S0140-6736(20)30609-7. [Article]
- Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME: Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020 Feb;145(2):572-582. doi: 10.1016/j.jaci.2019.08.042. Epub 2019 Oct 17. [Article]
- Shilling AD, Nedza FM, Emm T, Diamond S, McKeever E, Punwani N, Williams W, Arvanitis A, Galya LG, Li M, Shepard S, Rodgers J, Yue TY, Yeleswaram S: Metabolism, excretion, and pharmacokinetics of [14C]INCB018424, a selective Janus tyrosine kinase 1/2 inhibitor, in humans. Drug Metab Dispos. 2010 Nov;38(11):2023-31. doi: 10.1124/dmd.110.033787. Epub 2010 Aug 10. [Article]
- Shi JG, Chen X, Emm T, Scherle PA, McGee RF, Lo Y, Landman RR, McKeever EG Jr, Punwani NG, Williams WV, Yeleswaram S: The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in healthy volunteers. J Clin Pharmacol. 2012 Jun;52(6):809-18. doi: 10.1177/0091270011405663. Epub 2011 May 20. [Article]
- Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, Levy R, Williams W, Gottlieb A: Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012 Oct;67(4):658-64. doi: 10.1016/j.jaad.2011.12.018. Epub 2012 Jan 24. [Article]
- Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, Verbeek M, Fischer J, Otten V, Schmickl M, Maas-Bauer K, Finke J, Peschel C, Duyster J, Poeck H, Zeiser R, von Bubnoff N: Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood. 2014 Jun 12;123(24):3832-42. doi: 10.1182/blood-2013-12-543736. Epub 2014 Apr 7. [Article]
- Deshpande A, Reddy MM, Schade GO, Ray A, Chowdary TK, Griffin JD, Sattler M: Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia. 2012 Apr;26(4):708-15. doi: 10.1038/leu.2011.255. Epub 2011 Sep 16. [Article]
- Mughal TI, Girnius S, Rosen ST, Kumar S, Wiestner A, Abdel-Wahab O, Kiladjian JJ, Wilson WH, Van Etten RA: Emerging therapeutic paradigms to target the dysregulated Janus kinase/signal transducer and activator of transcription pathway in hematological malignancies. Leuk Lymphoma. 2014 Sep;55(9):1968-79. doi: 10.3109/10428194.2013.863307. Epub 2014 Feb 17. [Article]
- FDA Approved Drug Products: JAKAFI (ruxolitinib) tablets, for oral use [Link]
- Santa Cruz Biotechnology, Inc.: Ruxolitinib Safety Data Sheet [Link]
- LC Laboratories: Ruxolitinib Safety Data Sheet [Link]
- Drugs.com: Jakafi FDA Approval History [Link]
- Novartis: Novartis provides update on RUXCOVID study of ruxolitinib for hospitalized patients with COVID-19 [Link]
- BC Cancer - Ruxolitinib monograph [Link]
- EMA Approved Drug Products: Jakavi (ruxolitinib) oral tablets [Link]
- FDA Approved Drug Products: OPZELURA (ruxolitinib) cream, for topical use [Link]
- EMA Approved Drug Products: OPZELURA (ruxolitinib) Topical Cream [Link]
- External Links
- KEGG Drug
- D09959
- PubChem Compound
- 25126798
- PubChem Substance
- 175427129
- ChemSpider
- 25027389
- BindingDB
- 50355501
- 1193326
- ChEBI
- 66919
- ChEMBL
- CHEMBL1789941
- ZINC
- ZINC000043207851
- PharmGKB
- PA166123386
- PDBe Ligand
- RXT
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ruxolitinib
- PDB Entries
- 4u5j / 6vgl / 6vnk / 6wtn / 7f3g
- FDA label
- Download (399 KB)
- MSDS
- Download (210 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Post Polycythemia Vera Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / Primary Myelofibrosis (PMF) 1 4 Recruiting Prevention Graft-versus-host Disease (GVHD) 1 4 Recruiting Treatment Acute Myeloid Leukemia / Graft-versus-host Disease (GVHD) / Polycythemia Vera (PV) / Primary Myelofibrosis (PMF) / Thalassemia 1 4 Recruiting Treatment Atopic Dermatitis 1 4 Recruiting Treatment Cytokine Storm / Hemophagocytic Lymphohistiocytosis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10.0 mg/1 Tablet Oral 15.0 mg/1 Tablet Oral 20.0 mg/1 Tablet Oral 25.0 mg/1 Tablet Oral 5.0 mg/1 Tablet Oral 19.8 mg Tablet Oral 6.6 mg Tablet Oral 15 mg Tablet Oral 20 mg Tablet Oral 5 mg Tablet Oral Tablet Oral 10 mg Tablet Oral 1000000 mg Tablet Oral 2000000 mg Cream Cutaneous 15 mg/g Cream Topical 15 mg/1g - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7598257 Yes 2009-10-06 2028-06-24 US US8822481 Yes 2014-09-02 2028-12-12 US US8829013 Yes 2014-09-09 2028-12-12 US US9079912 Yes 2015-07-14 2027-06-12 US US8415362 Yes 2013-04-09 2028-06-24 US US8722693 Yes 2014-05-13 2028-12-12 US US9662335 No 2017-05-30 2026-12-12 US US10016429 Yes 2018-07-10 2028-12-12 US US9814722 Yes 2017-11-14 2027-06-12 US US9974790 Yes 2018-05-22 2027-06-12 US US10610530 Yes 2020-04-07 2028-12-12 US US10639310 Yes 2020-05-05 2027-06-12 US US10869870 Yes 2020-12-22 2031-11-20 US US10758543 Yes 2020-09-01 2031-11-20 US US11219624 Yes 2011-11-20 2031-11-20 US US11510923 No 2020-09-04 2040-09-04 US US11571425 No 2011-05-20 2031-05-20 US US11590136 No 2011-05-20 2031-05-20 US US11590137 No 2020-09-04 2040-09-04 US US11590138 No 2020-06-10 2040-06-10 US US11602536 No 2021-05-05 2041-05-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 86 MSDS boiling point (°C) 592.6 MSDS water solubility Soluble in aqueous buffers across a pH of 1-8 FDA label - Predicted Properties
Property Value Source Water Solubility 0.116 mg/mL ALOGPS logP 2.94 ALOGPS logP 2.48 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 13.89 Chemaxon pKa (Strongest Basic) 3.91 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 83.18 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 98.01 m3·mol-1 Chemaxon Polarizability 33.07 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9673 Caco-2 permeable - 0.5198 P-glycoprotein substrate Non-substrate 0.7838 P-glycoprotein inhibitor I Non-inhibitor 0.8228 P-glycoprotein inhibitor II Inhibitor 0.7092 Renal organic cation transporter Non-inhibitor 0.5098 CYP450 2C9 substrate Non-substrate 0.8394 CYP450 2D6 substrate Non-substrate 0.8075 CYP450 3A4 substrate Non-substrate 0.6535 CYP450 1A2 substrate Inhibitor 0.6426 CYP450 2C9 inhibitor Non-inhibitor 0.7731 CYP450 2D6 inhibitor Non-inhibitor 0.9208 CYP450 2C19 inhibitor Non-inhibitor 0.6689 CYP450 3A4 inhibitor Non-inhibitor 0.6655 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5753 Ames test AMES toxic 0.5681 Carcinogenicity Non-carcinogens 0.9308 Biodegradation Not ready biodegradable 0.9917 Rat acute toxicity 2.5724 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.633 hERG inhibition (predictor II) Non-inhibitor 0.8772
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0009000000-e061956fd8cac1731cd0 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0039000000-f768be23bba650537a6b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0arr-0193000000-d9dd0614d8244fa91643 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-1292000000-03e9230574c42a376b26 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05oa-0390000000-1cc47e9bbeec706a740b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-02al-1940000000-aedb326c4b72231b1389 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 188.106314 predictedDarkChem Lite v0.1.0 [M-H]- 167.28233 predictedDeepCCS 1.0 (2019) [M+H]+ 189.312114 predictedDarkChem Lite v0.1.0 [M+H]+ 169.64034 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.699014 predictedDarkChem Lite v0.1.0 [M+Na]+ 175.74132 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In vitro, ruxolitinib inhibited JAK2 with a mean half-maximal inhibitory concentration (IC50) of 2.8 nmol/L (Yang & Keating, 2012).
- General Function
- Sh2 domain binding
- Specific Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptiv...
- Gene Name
- JAK2
- Uniprot ID
- O60674
- Uniprot Name
- Tyrosine-protein kinase JAK2
- Molecular Weight
- 130672.475 Da
References
- 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. [Article]
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
- Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In vitro, ruxolitinib inhibited JAK1 with a mean half-maximal inhibitory concentration (IC50) of 3.3 nmol/L (Yang & Keating, 2012).
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
- Gene Name
- JAK1
- Uniprot ID
- P23458
- Uniprot Name
- Tyrosine-protein kinase JAK1
- Molecular Weight
- 133275.995 Da
References
- 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. [Article]
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
- Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In vitro, ruxolitinib inhibited JAK3 with a mean half-maximal inhibitory concentration (IC50) of 428 nmol/L (Yang & Keating, 2012).
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a...
- Gene Name
- JAK3
- Uniprot ID
- P52333
- Uniprot Name
- Tyrosine-protein kinase JAK3
- Molecular Weight
- 125097.565 Da
References
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
- Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In vitro, ruxolitinib inhibited TYK2 with a mean half-maximal inhibitory concentration (IC50) of 19 nmol/L (Yang & Keating, 2012).
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
- Gene Name
- TYK2
- Uniprot ID
- P29597
- Uniprot Name
- Non-receptor tyrosine-protein kinase TYK2
- Molecular Weight
- 133648.77 Da
References
- Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81. [Article]
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [Article]
- Becker H, Engelhardt M, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16. [Article]
- Ajayi S, Becker H, Reinhardt H, Engelhardt M, Zeiser R, von Bubnoff N, Wasch R: Ruxolitinib. Recent Results Cancer Res. 2018;212:119-132. doi: 10.1007/978-3-319-91439-8_6. [Article]
- FDA Approved Drug Products: JAKAFI (ruxolitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Umehara K, Huth F, Jin Y, Schiller H, Aslanis V, Heimbach T, He H: Drug-drug interaction (DDI) assessments of ruxolitinib, a dual substrate of CYP3A4 and CYP2C9, using a verified physiologically based pharmacokinetic (PBPK) model to support regulatory submissions. Drug Metab Pers Ther. 2019 May 30;34(2). pii: /j/dmdi.ahead-of-print/dmpt-2018-0042/dmpt-2018-0042.xml. doi: 10.1515/dmpt-2018-0042. [Article]
- FDA Approved Drug Products: JAKAFI (ruxolitinib) tablets, for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- FDA Approved Drug Products: JAKAFI (ruxolitinib) tablets, for oral use [Link]
Drug created at May 13, 2013 18:21 / Updated at February 20, 2024 23:54