Ruxolitinib

Identification

Name

Ruxolitinib

Accession Number

DB08877

Description

Ruxolitinib is a janus-associated kinase inhibitor indicated to treat bone marrow cancer, specifically intermediate or high-risk myelofibrosis. FDA approved on November 16, 2011.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Ruxolitinib (DB08877)

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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

Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis. [Lexicomp] Myeolofibrosis is the proliferation of abnormal bone marrow stem cells which cause fibrosis (the excessive formation of connective tissue).

Associated Conditions

• Post Essential Thrombocythaemia Myelofibrosis
• Post Polycythemia Vera Myelofibrosis
• High risk Myelofibrosis
• Intermediate risk Myelofibrosis
• Refractory Polycythemia vera

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

The mean half-maximal inhibitory concentration (IC50) for JAK 1 and JAK 2 are 2.8 nmol/L and 3.3 nmol/L respectively. After administration of ruxolitinib, a decrease in levels of phosphorylated STAT (marker for JAK activity) in a dose-dependent manner can be observed. Pharmacodynamic resistance has not been observed.

Mechanism of action

Ruxolitinib is a kinase inhibitor that is selective for the Janus Associated Kinases (JAK) 1 and 2. These kinases are responsible for the mediation of cytokine and growth factor signalling which in turn effect immune function and hematopoiesis. The signalling process involves signal transducers and transcription activators (STAT) which modulate gene expression. Patients with myelofibrosis have abnormal JAK1 and JAK2 activity thus ruxolitinib works to regulate this.

Target	Actions	Organism
ATyrosine-protein kinase JAK1	inhibitor	Humans
ATyrosine-protein kinase JAK2	inhibitor	Humans

Absorption

Absorption is rapid and is not affected by food. Cmax, 15 mg, healthy subject = 649 nmol/L; Tmax, 15 mg, healthy subject = 1.5 hours; Ruxolitinib does not accumulate significantly.

Volume of distribution

Terminal phase volume of distribution, 15 mg, healthy subject = 76.6 L.

Protein binding

97% protein bound, primarily to albumin.

Metabolism

Ruxolitinib is metabolized by CYP3A4. Less potent active metabolites forms as a result.

Route of elimination

Eliminated via urine (74%, <1% as unchanged drug) and feces (22%, <1% as unchanged drug).

Half-life

Mean elimination half-life, 15 mg, healthy subject = 2.8 hours.

Clearance

15 mg, healthy subject = 18.7 L/h.

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

Thrombocytopenia was the dose-limiting toxicity.

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
Abaloparatide	The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Ruxolitinib.
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.
Acalabrutinib	The metabolism of Ruxolitinib can be decreased when combined with Acalabrutinib.
Acarbose	Acarbose may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
Acebutolol	Ruxolitinib may increase the bradycardic activities of Acebutolol.
Aceclofenac	Aceclofenac may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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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.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Ruxolitinib phosphate	436LRU32H5	1092939-17-7	JFMWPOCYMYGEDM-XFULWGLBSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Jakafi	Tablet	10.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	20.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	5.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	25.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	15.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakavi	Tablet	5 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet		Oral	Novartis	2015-04-15	Not applicable
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

L01XE18 — Ruxolitinib

• L01XE — Protein kinase inhibitors
• L01X — OTHER ANTINEOPLASTIC AGENTS
• L01 — ANTINEOPLASTIC AGENTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 Substrates
• Drugs that are Mainly Renally Excreted
• Immunosuppressive Agents
• 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)

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[[email protected]](C1CCCC1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1

References

General References

1. 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. [PubMed:23514013]
2. Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [PubMed:23061804]

External Links

KEGG Drug

D09959

PubChem Compound

25126798

PubChem Substance

175427129

ChemSpider

25027389

BindingDB

50355501

RxNav

1193326

ChEBI

66919

ChEMBL

CHEMBL1789941

ZINC

ZINC000043207851

PharmGKB

PA166123386

PDBe Ligand

RXT

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Ruxolitinib

AHFS Codes

• 10:00.00 — Antineoplastic Agents

PDB Entries

4u5j

FDA label

Download (399 KB)

MSDS

Download (210 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Post Essential Thrombocythaemia Myelofibrosis (PET-MF) / Post Polycythaemia Myelofibrosis (PPV MF) / Primary Myelofibrosis (PMF)	1
4	Recruiting	Treatment	Chronic Idiopathic Myelofibrosis / Post Essential Thrombocythaemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis / Steroid Refractory Graft Versus Host Disease	1
4	Recruiting	Treatment	Safety and Efficacy	1
4	Recruiting	Treatment	Thalassemia Major (TM)	1
3	Active Not Recruiting	Treatment	Atopic Dermatitis (AD)	2
3	Active Not Recruiting	Treatment	Corticosteroid Refractory Acute Graft vs Host Disease	1
3	Active Not Recruiting	Treatment	Graft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)	1
3	Completed	Treatment	Agnogenic Myeloid Metaplasia	2
3	Completed	Treatment	MPN (Myeloproliferative Neoplasms)	1
3	Completed	Treatment	Polycythemia Vera (PV)	4

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
Tablet	Oral	10 mg
Tablet	Oral	15 mg
Tablet	Oral	20 mg
Tablet	Oral	5 mg
Tablet		10 mg
Tablet		15 mg
Tablet		20 mg
Tablet		5 mg
Tablet

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US7598257	No	2009-10-06	2027-12-24
US8822481	No	2014-09-02	2028-06-12
US8829013	No	2014-09-09	2028-06-12
US9079912	No	2015-07-14	2026-12-12
US8415362	No	2013-04-09	2027-12-24
US8722693	No	2014-05-13	2028-06-12
US9662335	No	2017-05-30	2026-12-12
US10016429	No	2018-07-10	2028-06-12
US9814722	No	2017-11-14	2026-12-12

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Property	Value	Source
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)	5.51	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	33.04 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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on May 13, 2013 12:21 / Updated on October 21, 2020 01:55