Ruxolitinib

Overview

Ruxolitinib (sold under the brand names Jakafi and Jakavi among others, and as Opzelura in cream form) is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.[1–5] WP

It was approved for medical use in the United States in 2011, and in the European Union in 2012. Ruxolitinib is the first FDA-approved pharmacologic treatment to address repigmentation in vitiligo patients.[6][7][8] WP

The crystal structure of ruxolitinib and of its dihydrate form are known.[9] WP

Uses, dosage and effects

Medical uses

In the United States and the European Union, ruxolitinib is indicated for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis. It is also indicated for the treatment of adults with polycythaemia vera who are resistant to or intolerant of hydroxyurea. Ruxolitinib is also indicated for the treatment of steroid-refractory acute graft-versus-host disease in people who are twelve years of age and older, and for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in people twelve years of age and older. It is commonly given as an oral tablet.[1][7][10][11] WP⚠ Wikipedia itself has flagged this text: citation needed.

In the United States, ruxolitinib cream is indicated for the topical treatment of mild to moderate atopic dermatitis and vitiligo. In the European Union, ruxolitinib cream is indicated for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age.[12][13] WP

Risks and side effects

Side effects

In myelofibrosis, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), neutropenia (low levels of neutrophils), urinary tract infections (infection of the kidney, renal pelvis, ureter, bladder or urethra), bleeding, bruising, weight gain, hypercholesterolaemia (high blood cholesterol levels), dizziness, headache and raised liver enzyme levels.[7] WP

In polycythaemia vera, the most common side effects include anemia (low red blood cell counts) and thrombocytopenia (low blood platelet count), bleeding, bruising, hypercholesterolaemia (high blood cholesterol levels), hypertriglyceridemia (high blood fat levels), dizziness, raised liver enzyme levels and high blood pressure.[7] WP

In acute graft-versus-host disease, the most common hematologic adverse reactions include anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions include infections and edema.[1] WP

Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. Other viruses, such as LCMV and HSV1, were shown to replicate better in presence of ruxolitinib, this effect was counteracted by host-directed antiviral, NMT-inhibitors such as DDD85646, the analogue of IMP-1088. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels.[1][14][15] WP

Pharmacology

Mechanism of action

Ruxolitinib is a Janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. 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.[1][16][17] WP

Research

Research

It is being investigated for plaque psoriasis, alopecia areata, relapsed diffuse large B-cell lymphoma, peripheral T-cell lymphoma., and large granular lymphocyte leukemia.[16][18][19] WP

In February 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy.[20] WP

Eight weeks-treatment with ruxolitinib blunted senescent cell-mediated inhibition of adipogenesis and increased insulin sensitivity in 22-month-old mice.[21] WP

As of September 2019, a clinical trial is in progress to evaluate "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".[22] WP

Opportunistic and acquired viral infection (such as herpes zoster, LCMV and HSV1) is a risk that requires pausing JAK inhibitors treatment, treating the infection, research in cell based assays this effect was counteracted by host-directed antiviral, NMT-inhibitors such DDD85646, the analogue of IMP-1088.[15] WP

History

History

In March 2012, 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.[23–26] WP

Legal status

Legal status

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.[6][27] WP

In 2014, it was approved in polycythemia vera when there has been an inadequate response to or intolerance of hydroxyurea, based on the RESPONSE trial.[4][28] WP

In May 2019, the indication for ruxolitinib was expanded in the US to include steroid-refractory acute graft-versus-host disease. The indication was further expanded in the US in September 2021, for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in people 12 years of age and older.[10][29] WP

In September 2021, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of mild to moderate atopic dermatitis (AD). It is the first topical Janus kinase inhibitor approved in the United States.[30][31] WP

In July 2022, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of vitiligo.[8][32] WP

On 23 February 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Opzelura, intended for the treatment of non-segmental vitiligo. The applicant for this medicinal product is Incyte Biosciences Distribution B.V.[33] WP

Chemistry

Formula

C17H18N6 PC

CAS number

941678-49-5 PC

Molar mass (g/mol)

306.4 PC

IUPAC name (computed by PubChem)

(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile PC

SMILES

C1CCC(C1)[C@@H](CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3 PC

InChIKey

HFNKQEVNSGCOJV-OAHLLOKOSA-N PC

PubChem CID

25126798

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Jakafi- ruxolitinib tablet. 26 February 2020
2. Journal / agency Mesa RA, Yasothan U, Kirkpatrick P. Ruxolitinib. Nature Reviews. Drug Discovery. February 2012. doi:10.1038/nrd3652 · PMID 22293561
3. Journal / agency Harrison C, Mesa R, Ross D, Mead A, Keohane C, Gotlib J, Verstovsek S. Practical management of patients with myelofibrosis receiving ruxolitinib. Expert Review of Hematology. October 2013. doi:10.1586/17474086.2013.827413 · PMID 24083419 · PMC8201600
4. Journal / agency Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. The New England Journal of Medicine. January 2015. doi:10.1056/NEJMoa1409002 · PMID 25629741 · PMC4358820
5. Other FDA Approves Jakafi® (Ruxolitinib) for the Treatment of Patients with Uncontrolled Polycythemia Vera. 4 December 2014
6. Journal / agency Drug Approval Package: Jakafi (ruxolitinib) Tablets NDA # 202192
7. Journal / agency Jakavi EPAR. 17 September 2018
8. Journal / agency FDA approves topical treatment. 19 July 2022
9. Journal / agency Peng Z, Ye L. Comparison of the crystal structures of the JAK1/2 inhibitor ruxolitinib and its hydrate and phosphate. Acta Crystallographica Section C. August 2024. doi:10.1107/S2053229624006740 · PMID 39046815
10. Journal / agency FDA approves ruxolitinib for chronic graft-versus-host disease. 22 September 2021
11. Other EU Commission Approval. 5 May 2022
12. Journal / agency Opzelura- ruxolitinib cream
13. Journal / agency Opzelura EPAR. 20 April 2023
14. Journal / agency Wysham NG, Sullivan DR, Allada G. An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor. Chest. May 2013. doi:10.1378/chest.12-1604 · PMID 23648912 · PMC5991580
15. Journal / agency Witwit H, de la Torre JC. N-myristoyltransferase inhibitors as candidate broad-spectrum antivirals to treat viral infections promoted by immunosuppression associated with JAK inhibitors therapy. Antiviral Research. October 2025. doi:10.1016/j.antiviral.2025.106258 · PMID 40803634
16. Journal / agency Mesa RA. Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis. IDrugs. June 2010. PMID 20506062
17. Journal / agency Pardanani A, Tefferi A. Targeting myeloproliferative neoplasms with JAK inhibitors. Current Opinion in Hematology. March 2011. doi:10.1097/MOH.0b013e3283439964 · PMID 21245760
18. Journal / agency Falto-Aizpurua L, Choudhary S, Tosti A. Emerging treatments in alopecia. Expert Opinion on Emerging Drugs. December 2014. doi:10.1517/14728214.2014.974550 · PMID 25330928
19. Other ClinicalTrialsGov NCT01431209 Ruxolitinib Phosphate (Oral JAK Inhibitor INCB18424) in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma
20. Other House DW. Incyte bags late-stage development of Jakafi for solid tumors; shares down 10% premarket. February 2016
21. Journal / agency Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL. Targeting senescent cells enhances adipogenesis and metabolic function in old age. eLife. December 2015. doi:10.7554/eLife.12997 · PMID 26687007 · PMC4758946
22. Other ClinicalTrialsGov NCT03610971 Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors
23. Journal / agency Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. The New England Journal of Medicine. March 2012. doi:10.1056/NEJMoa1110556 · PMID 22375970
24. Journal / agency Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. The New England Journal of Medicine. March 2012. doi:10.1056/NEJMoa1110557 · PMID 22375971 · PMC4822164
25. Journal / agency Tefferi A. Challenges facing JAK inhibitor therapy for myeloproliferative neoplasms. The New England Journal of Medicine. March 2012. doi:10.1056/NEJMe1115119 · PMID 22375977
26. Other ASCO Annual Meeting 2011: JAK Inhibitor Ruxolitinib Demonstrates Significant Clinical Benefit in Myelofibrosis. link 2
27. Other FDA Approves Incyte's Jakafi (ruxolitinib) for Patients with Myelofibrosis
28. Journal / agency Kaminskas E. Supplemental FDA approval letter for Jakafi (ruxolitinib) tablets. 4 December 2014
29. Journal / agency FDA approves ruxolitinib for acute graft-versus-host disease. 24 May 2019
30. Journal / agency Drug Approval Package: OPZELURA
31. Other Incyte Announces U.S. FDA Approval of Opzelura (ruxolitinib) Cream, a Topical JAK Inhibitor, for the Treatment of Atopic Dermatitis (AD). 21 September 2021
32. Other Incyte Announces U.S. FDA Approval of Opzelura (ruxolitinib) Cream for the Treatment of Vitiligo. 19 July 2022
33. Journal / agency Opzelura: Pending EC decision. 24 February 2023

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