Ruxolitinib - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (2)Enzymes (1)

Targets (2)Enzymes (1)Biointeractions (3)

Identification

Name

Ruxolitinib

Accession Number

DB08877

Type

Small Molecule

Groups

Approved

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.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

INCB424

External IDs

INC-424 / INC424 / INCB 18424 / INCB-018424 / INCB-18424 / INCB018424

Product Ingredients

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

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Jakafi	Tablet	5 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable	US
Jakafi	Tablet	20 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable	US
Jakafi	Tablet	10 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable	US
Jakafi	Tablet	25 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable	US
Jakafi	Tablet	15 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable	US
Jakavi	Tablet	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	10 mg	Oral	Novartis	2015-04-15	Not applicable	Canada
Jakavi	Tablet	10 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	5 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	10 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	15 mg	Oral	Novartis	2012-07-19	Not applicable	Canada
Jakavi	Tablet	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	5 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	10 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	20 mg	Oral	Novartis	2012-07-19	Not applicable	Canada
Jakavi	Tablet	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	5 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU
Jakavi	Tablet	5 mg	Oral	Novartis	2012-07-19	Not applicable	Canada
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable	EU

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

82S8X8XX8H

CAS number

941678-49-5

Weight

Average: 306.365
Monoisotopic: 306.159294606

Chemical Formula

C₁₇H₁₈N₆

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

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).

Structured Indications

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	Kind	Pharmacological action	Actions	Organism	UniProt ID
Tyrosine-protein kinase JAK1	Protein	yes	inhibitor	Human	P23458	details
Tyrosine-protein kinase JAK2	Protein	yes	inhibitor	Human	O60674	details

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.

Toxicity

Thrombocytopenia was the dose-limiting toxicity.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Acebutolol	Ruxolitinib may increase the bradycardic activities of Acebutolol.	Approved
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Ruxolitinib.	Approved
Amiodarone	The serum concentration of Ruxolitinib can be increased when it is combined with Amiodarone.	Approved, Investigational
Aprepitant	The serum concentration of Ruxolitinib can be increased when it is combined with Aprepitant.	Approved, Investigational
Atazanavir	The serum concentration of Ruxolitinib can be increased when it is combined with Atazanavir.	Approved, Investigational
Atenolol	Ruxolitinib may increase the bradycardic activities of Atenolol.	Approved
Atomoxetine	The metabolism of Ruxolitinib can be decreased when combined with Atomoxetine.	Approved
Bendroflumethiazide	Ruxolitinib may increase the bradycardic activities of Bendroflumethiazide.	Approved
Beractant	Ruxolitinib may increase the bradycardic activities of Beractant.	Approved
Betaxolol	Ruxolitinib may increase the bradycardic activities of Betaxolol.	Approved
Bevacizumab	Bevacizumab may increase the cardiotoxic activities of Ruxolitinib.	Approved, Investigational
Bexarotene	The serum concentration of Ruxolitinib can be decreased when it is combined with Bexarotene.	Approved, Investigational
Bisoprolol	Ruxolitinib may increase the bradycardic activities of Bisoprolol.	Approved
Boceprevir	The serum concentration of Ruxolitinib can be increased when it is combined with Boceprevir.	Approved, Investigational
Bortezomib	The metabolism of Ruxolitinib can be decreased when combined with Bortezomib.	Approved, Investigational
Bosentan	The serum concentration of Ruxolitinib can be decreased when it is combined with Bosentan.	Approved, Investigational
Cabazitaxel	The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ruxolitinib.	Approved
Calfactant	Ruxolitinib may increase the bradycardic activities of Calfactant.	Approved
Carbamazepine	The metabolism of Ruxolitinib can be increased when combined with Carbamazepine.	Approved, Investigational
Carteolol	Ruxolitinib may increase the bradycardic activities of Carteolol.	Approved
Carvedilol	Ruxolitinib may increase the bradycardic activities of Carvedilol.	Approved, Investigational
Ceritinib	The serum concentration of Ruxolitinib can be increased when it is combined with Ceritinib.	Approved
Clarithromycin	The serum concentration of Ruxolitinib can be increased when it is combined with Clarithromycin.	Approved
Clemastine	The metabolism of Ruxolitinib can be decreased when combined with Clemastine.	Approved
Clonidine	Ruxolitinib may increase the bradycardic activities of Clonidine.	Approved
Clotrimazole	The metabolism of Ruxolitinib can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Clozapine	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Clozapine.	Approved
Cobicistat	The serum concentration of Ruxolitinib can be increased when it is combined with Cobicistat.	Approved
Conivaptan	The serum concentration of Ruxolitinib can be increased when it is combined with Conivaptan.	Approved, Investigational
Crizotinib	Ruxolitinib may increase the bradycardic activities of Crizotinib.	Approved
Cyclophosphamide	Cyclophosphamide may increase the cardiotoxic activities of Ruxolitinib.	Approved, Investigational
Cyclosporine	The metabolism of Ruxolitinib can be decreased when combined with Cyclosporine.	Approved, Investigational, Vet Approved
Dabrafenib	The serum concentration of Ruxolitinib can be decreased when it is combined with Dabrafenib.	Approved
Darunavir	The serum concentration of Ruxolitinib can be increased when it is combined with Darunavir.	Approved
Dasatinib	The serum concentration of Ruxolitinib can be increased when it is combined with Dasatinib.	Approved, Investigational
Deferasirox	The serum concentration of Ruxolitinib can be decreased when it is combined with Deferasirox.	Approved, Investigational
Delavirdine	The metabolism of Ruxolitinib can be decreased when combined with Delavirdine.	Approved
Denosumab	The risk or severity of adverse effects can be increased when Denosumab is combined with Ruxolitinib.	Approved
Deslanoside	Deslanoside may decrease the cardiotoxic activities of Ruxolitinib.	Approved
Dexamethasone	The serum concentration of Ruxolitinib can be decreased when it is combined with Dexamethasone.	Approved, Investigational, Vet Approved
Dexmedetomidine	Ruxolitinib may increase the bradycardic activities of Dexmedetomidine.	Approved, Vet Approved
Digitoxin	Digitoxin may decrease the cardiotoxic activities of Ruxolitinib.	Approved
Digoxin	Ruxolitinib may increase the bradycardic activities of Digoxin.	Approved
Dihydroergotamine	The metabolism of Ruxolitinib can be decreased when combined with Dihydroergotamine.	Approved
Diltiazem	Ruxolitinib may increase the bradycardic activities of Diltiazem.	Approved
Docetaxel	The risk or severity of adverse effects can be increased when Docetaxel is combined with Ruxolitinib.	Approved, Investigational
Donepezil	Ruxolitinib may increase the bradycardic activities of Donepezil.	Approved
Doxycycline	The metabolism of Ruxolitinib can be decreased when combined with Doxycycline.	Approved, Investigational, Vet Approved
Dronedarone	Ruxolitinib may increase the bradycardic activities of Dronedarone.	Approved
Efavirenz	The serum concentration of Ruxolitinib can be decreased when it is combined with Efavirenz.	Approved, Investigational
Enzalutamide	The serum concentration of Ruxolitinib can be decreased when it is combined with Enzalutamide.	Approved
Erythromycin	The metabolism of Ruxolitinib can be decreased when combined with Erythromycin.	Approved, Vet Approved
Eslicarbazepine acetate	The serum concentration of Ruxolitinib can be decreased when it is combined with Eslicarbazepine acetate.	Approved
Esmolol	Ruxolitinib may increase the bradycardic activities of Esmolol.	Approved
Etravirine	The serum concentration of Ruxolitinib can be decreased when it is combined with Etravirine.	Approved
Fingolimod	Ruxolitinib may increase the immunosuppressive activities of Fingolimod.	Approved, Investigational
Fluconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Fluconazole.	Approved
Fluvoxamine	The metabolism of Ruxolitinib can be decreased when combined with Fluvoxamine.	Approved, Investigational
Fosamprenavir	The metabolism of Ruxolitinib can be decreased when combined with Fosamprenavir.	Approved
Fosaprepitant	The serum concentration of Ruxolitinib can be increased when it is combined with Fosaprepitant.	Approved
Fosphenytoin	The metabolism of Ruxolitinib can be increased when combined with Fosphenytoin.	Approved
Fusidic Acid	The serum concentration of Ruxolitinib can be increased when it is combined with Fusidic Acid.	Approved
G17DT	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with G17DT.	Investigational
Galantamine	Ruxolitinib may increase the bradycardic activities of Galantamine.	Approved
Guanfacine	Ruxolitinib may increase the bradycardic activities of Guanfacine.	Approved, Investigational
Idelalisib	The serum concentration of Ruxolitinib can be increased when it is combined with Idelalisib.	Approved
Imatinib	The metabolism of Ruxolitinib can be decreased when combined with Imatinib.	Approved
Indinavir	The serum concentration of Ruxolitinib can be increased when it is combined with Indinavir.	Approved
INGN 201	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with INGN 201.	Investigational
INGN 225	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with INGN 225.	Investigational
Isavuconazonium	The metabolism of Ruxolitinib can be decreased when combined with Isavuconazonium.	Approved, Investigational
Isradipine	The metabolism of Ruxolitinib can be decreased when combined with Isradipine.	Approved
Itraconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Itraconazole.	Approved, Investigational
Ivabradine	Ruxolitinib may increase the bradycardic activities of Ivabradine.	Approved
Ivacaftor	The serum concentration of Ruxolitinib can be increased when it is combined with Ivacaftor.	Approved
Ketoconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Ketoconazole.	Approved, Investigational
Labetalol	Ruxolitinib may increase the bradycardic activities of Labetalol.	Approved
Lanreotide	Ruxolitinib may increase the bradycardic activities of Lanreotide.	Approved
Leflunomide	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Leflunomide.	Approved, Investigational
Levobunolol	Ruxolitinib may increase the bradycardic activities of Levobunolol.	Approved
Lopinavir	The serum concentration of Ruxolitinib can be increased when it is combined with Lopinavir.	Approved
Lovastatin	The metabolism of Ruxolitinib can be decreased when combined with Lovastatin.	Approved, Investigational
Lucinactant	Ruxolitinib may increase the bradycardic activities of Lucinactant.	Approved
Luliconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Luliconazole.	Approved
Lumacaftor	The metabolism of Ruxolitinib can be increased when combined with Lumacaftor.	Approved
Metamizole	The risk or severity of adverse effects can be increased when Metamizole is combined with Ruxolitinib.	Withdrawn
Methyldopa	Ruxolitinib may increase the bradycardic activities of Methyldopa.	Approved
Metipranolol	Ruxolitinib may increase the bradycardic activities of Metipranolol.	Approved
Metoprolol	Ruxolitinib may increase the bradycardic activities of Metoprolol.	Approved, Investigational
Mifepristone	The serum concentration of Ruxolitinib can be increased when it is combined with Mifepristone.	Approved, Investigational
Mitotane	The serum concentration of Ruxolitinib can be decreased when it is combined with Mitotane.	Approved
Modafinil	The serum concentration of Ruxolitinib can be decreased when it is combined with Modafinil.	Approved, Investigational
Nadolol	Ruxolitinib may increase the bradycardic activities of Nadolol.	Approved
Nafcillin	The serum concentration of Ruxolitinib can be decreased when it is combined with Nafcillin.	Approved
Natalizumab	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Natalizumab.	Approved, Investigational
Nebivolol	Ruxolitinib may increase the bradycardic activities of Nebivolol.	Approved, Investigational
Nefazodone	The serum concentration of Ruxolitinib can be increased when it is combined with Nefazodone.	Approved, Withdrawn
Nelfinavir	The serum concentration of Ruxolitinib can be increased when it is combined with Nelfinavir.	Approved
Netupitant	The serum concentration of Ruxolitinib can be increased when it is combined with Netupitant.	Approved
Nevirapine	The metabolism of Ruxolitinib can be increased when combined with Nevirapine.	Approved
Nilotinib	The metabolism of Ruxolitinib can be decreased when combined with Nilotinib.	Approved, Investigational
Octreotide	Ruxolitinib may increase the bradycardic activities of Octreotide.	Approved, Investigational
Olaparib	The metabolism of Ruxolitinib can be decreased when combined with Olaparib.	Approved
Oleandrin	Anvirzel may decrease the cardiotoxic activities of Ruxolitinib.	Experimental
Osimertinib	The serum concentration of Ruxolitinib can be increased when it is combined with Osimertinib.	Approved
Ouabain	Ouabain may decrease the cardiotoxic activities of Ruxolitinib.	Approved
Paclitaxel	The risk or severity of adverse effects can be increased when Paclitaxel is combined with Ruxolitinib.	Approved, Vet Approved
Palbociclib	The serum concentration of Ruxolitinib can be increased when it is combined with Palbociclib.	Approved
Pasireotide	Ruxolitinib may increase the bradycardic activities of Pasireotide.	Approved
Penbutolol	Ruxolitinib may increase the bradycardic activities of Penbutolol.	Approved, Investigational
Pentobarbital	The metabolism of Ruxolitinib can be increased when combined with Pentobarbital.	Approved, Vet Approved
Phenobarbital	The metabolism of Ruxolitinib can be increased when combined with Phenobarbital.	Approved
Phenytoin	The metabolism of Ruxolitinib can be increased when combined with Phenytoin.	Approved, Vet Approved
Pimecrolimus	The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Ruxolitinib.	Approved, Investigational
Pindolol	Ruxolitinib may increase the bradycardic activities of Pindolol.	Approved
Poractant alfa	Ruxolitinib may increase the bradycardic activities of Poractant alfa.	Approved
Posaconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Posaconazole.	Approved, Investigational, Vet Approved
Primidone	The metabolism of Ruxolitinib can be increased when combined with Primidone.	Approved, Vet Approved
Propafenone	Ruxolitinib may increase the bradycardic activities of Propafenone.	Approved
Propranolol	Ruxolitinib may increase the bradycardic activities of Propranolol.	Approved, Investigational
Ranolazine	The metabolism of Ruxolitinib can be decreased when combined with Ranolazine.	Approved, Investigational
Rifabutin	The metabolism of Ruxolitinib can be increased when combined with Rifabutin.	Approved
Rifampicin	The metabolism of Ruxolitinib can be increased when combined with Rifampicin.	Approved
Rifapentine	The metabolism of Ruxolitinib can be increased when combined with Rifapentine.	Approved
Rindopepimut	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with CDX-110.	Investigational
Ritonavir	The serum concentration of Ruxolitinib can be increased when it is combined with Ritonavir.	Approved, Investigational
Rivastigmine	Ruxolitinib may increase the bradycardic activities of Rivastigmine.	Approved, Investigational
Roflumilast	Roflumilast may increase the immunosuppressive activities of Ruxolitinib.	Approved
Saquinavir	The serum concentration of Ruxolitinib can be increased when it is combined with Saquinavir.	Approved, Investigational
Sildenafil	The metabolism of Ruxolitinib can be decreased when combined with Sildenafil.	Approved, Investigational
Siltuximab	The serum concentration of Ruxolitinib can be decreased when it is combined with Siltuximab.	Approved
Simeprevir	The serum concentration of Ruxolitinib can be increased when it is combined with Simeprevir.	Approved
Sipuleucel-T	The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Ruxolitinib.	Approved
Sotalol	Ruxolitinib may increase the bradycardic activities of Sotalol.	Approved
SRP 299	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with SRP 299.	Investigational
St. John's Wort	The serum concentration of Ruxolitinib can be decreased when it is combined with St. John's Wort.	Nutraceutical
Stiripentol	The serum concentration of Ruxolitinib can be increased when it is combined with Stiripentol.	Approved
Sufentanil	Ruxolitinib may increase the bradycardic activities of Sufentanil.	Approved, Investigational
Sulfisoxazole	The metabolism of Ruxolitinib can be decreased when combined with Sulfisoxazole.	Approved, Vet Approved
Tacrolimus	The risk or severity of adverse effects can be increased when Tacrolimus is combined with Ruxolitinib.	Approved, Investigational
Telaprevir	The serum concentration of Ruxolitinib can be increased when it is combined with Telaprevir.	Withdrawn
Telithromycin	The serum concentration of Ruxolitinib can be increased when it is combined with Telithromycin.	Approved
Ticlopidine	The metabolism of Ruxolitinib can be decreased when combined with Ticlopidine.	Approved
Timolol	Ruxolitinib may increase the bradycardic activities of Timolol.	Approved
Tizanidine	Ruxolitinib may increase the bradycardic activities of Tizanidine.	Approved
Tocilizumab	The serum concentration of Ruxolitinib can be decreased when it is combined with Tocilizumab.	Approved
Tofacitinib	Ruxolitinib may increase the immunosuppressive activities of Tofacitinib.	Approved, Investigational
Trastuzumab	Trastuzumab may increase the cardiotoxic activities of Ruxolitinib.	Approved, Investigational
Venlafaxine	The metabolism of Ruxolitinib can be decreased when combined with Venlafaxine.	Approved
Verapamil	Ruxolitinib may increase the bradycardic activities of Verapamil.	Approved
Voriconazole	The serum concentration of Ruxolitinib can be increased when it is combined with Voriconazole.	Approved, Investigational
Ziprasidone	The metabolism of Ruxolitinib can be decreased when combined with Ziprasidone.	Approved

Food Interactions

Take without regards to meals

References

Synthesis Reference

Not Available

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. [PubMed:23514013 ]
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

Resource	Link
KEGG Drug	D09959
PubChem Compound	25126798
PubChem Substance	175427129
ChemSpider	25027389
BindingDB	50355501
ChEBI	66919
ChEMBL	CHEMBL1789941
HET	RXT
Drug Product Database	21376
RxList	http://www.rxlist.com/jakafi-drug.htm
Drugs.com	http://www.drugs.com/mtm/ruxolitinib.html
Wikipedia	Ruxolitinib

ATC Codes

L01XE18

AHFS Codes

10:00

PDB Entries

Not Available

FDA label

Download (399 KB)

MSDS

Download (210 KB)

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Hemophagocytic Syndrome (HPS)	1
0	Withdrawn	Treatment	Head and Neck Squamous Cell Carcinoma (HNSCC)	1
1	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	2
1	Active Not Recruiting	Treatment	Chronic Phase Chronic Myeloid Leukemia	1
1	Active Not Recruiting	Treatment	Idiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis	1
1	Active Not Recruiting	Treatment	Leukemias	1
1	Active Not Recruiting	Treatment	Metastatic Cancers / Pancreatic Cancer Metastatic	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Treatment	Chronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Childhood Solid Tumor, Protocol Specific	1
1	Not Yet Recruiting	Treatment	Breast Carcinoma Metastatic in the Bone / Estrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma	1
1	Recruiting	Health Services Research	Agnogenic Myeloid Metaplasia	1
1	Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL)	1
1	Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
1	Recruiting	Treatment	Agnogenic Myeloid Metaplasia / Polycythemia Vera (PV)	1
1	Recruiting	Treatment	Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)	1
1	Withdrawn	Supportive Care	Acute myeloid leukaemia (in remission) / Primary Myelofibrosis / Primary Myelofibrosis, Prefibrotic Stage / Secondary Acute Myeloid Leukemia / Secondary Myelofibrosis	1
1, 2	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
1, 2	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia / Polycythemia Vera (PV) / Thrombocytosis	1
1, 2	Active Not Recruiting	Treatment	Blood Platelet Disorders / Bone Marrow Diseases / Disorders, Blood Coagulation / Essential Thrombocythemia (ET) / Hematologic Diseases / Hemorrhagic Disorders / Myeloproliferative Disorders / Primary Myelofibrosis / Thrombocytosis	1
1, 2	Active Not Recruiting	Treatment	Chronic Myeloid Leukemia (CML)	1
1, 2	Active Not Recruiting	Treatment	Lung Cancers	1
1, 2	Active Not Recruiting	Treatment	Metastatic Breast Cancer (MBC) / Recurrent Breast Cancer	1
1, 2	Active Not Recruiting	Treatment	Myelomonocytic Leukemia	1
1, 2	Completed	Treatment	Chronic Lymphocytic Leukaemia (CLL)	1
1, 2	Completed	Treatment	Leukemias	1
1, 2	Not Yet Recruiting	Treatment	Chronic Myeloid Leukemia (CML)	1
1, 2	Not Yet Recruiting	Treatment	Leukemia, Lymphocytic, Chronic, B-Cell	1
1, 2	Recruiting	Treatment	Accelerated phase chronic myologenic leukemia / Blastic Phase Chronic Myeloid Leukemia / Chronic Phase Chronic Myeloid Leukemia / Philadelphia Positive Acute Lymphoblastic Leukemia / Resistant to Tyrosine Kinase Inhibitor Therapy	1
1, 2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia	2
1, 2	Recruiting	Treatment	Cancer, Advanced	1
1, 2	Recruiting	Treatment	Carcinoma, Breast / HER-2 Positive Breast Cancer / Metastatic Breast Cancer (MBC)	1
1, 2	Recruiting	Treatment	Fallopian Tube Carcinosarcoma / Fallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Serous Neoplasm / High Grade Ovarian Serous Adenocarcinoma / Ovarian Carcinosarcoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Stage III Fallopian Tube Cancer / Stage III Ovarian Cancer / Stage III Primary Peritoneal Cancer / Stage IIIA Fallopian Tube Cancer / Stage IIIA Ovarian Cancer / Stage IIIA Primary Peritoneal Cancer / Stage IIIB Fallopian Tube Cancer / Stage IIIB Ovarian Cancer / Stage IIIB Primary Peritoneal Cancer / Stage IIIC Fallopian Tube Cancer / Stage IIIC Ovarian Cancer / Stage IIIC Primary Peritoneal Cancer / Stage IV Fallopian Tube Cancer / Stage IV Ovarian Cancer / Stage IV Primary Peritoneal Cancer	1
1, 2	Recruiting	Treatment	Leukemias	1
1, 2	Recruiting	Treatment	Leukemias / Myeloproliferative Diseases	1
1, 2	Recruiting	Treatment	Myeloproliferative Disorders / Primary Myelofibrosis	1
1, 2	Recruiting	Treatment	Myeloproliferative Neoplasms	1
1, 2	Recruiting	Treatment	PMF / Post-ET MF / Post-PV MF / Primary Myelofibrosis / Secondary Myelofibrosis / SMF	1
2	Active Not Recruiting	Supportive Care	Anemias / Primary Myelofibrosis / Secondary Myelofibrosis	1
2	Active Not Recruiting	Treatment	Advanced or Metastatic HER2-negative Breast Cancer	1
2	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
2	Active Not Recruiting	Treatment	Cancer Cachexia	1
2	Active Not Recruiting	Treatment	Essential Thrombocythemia (ET) / Polycythemia Vera (PV)	1
2	Active Not Recruiting	Treatment	Estrogen-receptor Positive Invasive Metastatic Breast Cancer	1
2	Active Not Recruiting	Treatment	Lymphoma, Hodgkins	1
2	Active Not Recruiting	Treatment	Metastatic Cancers	1
2	Active Not Recruiting	Treatment	Metastatic Colorectal Cancers	1
2	Active Not Recruiting	Treatment	Myeloproliferative Diseases	2
2	Active Not Recruiting	Treatment	Non-Small-Cell Lung Carcinoma (NSCLC)	1
2	Active Not Recruiting	Treatment	Pancreatic Adenocarcinoma Metastatic	1
2	Active Not Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
2	Active Not Recruiting	Treatment	Post-Essential Thrombocythemia (ET) MF / Post-Polycythemia Vera (PV) MF / Primary Myelofibrosis (MF)	1
2	Active Not Recruiting	Treatment	Primary mediastinal large B-cell lymphomas / Relapsed or Refractory Hodgkin Lymphoma	1
2	Completed	Treatment	Acute Lymphocytic Leukemia (ALL) / Acute Myeloid Leukaemias (AML) / Chronic Myelogenous Leukemia (CML) / Myelodysplastic Syndrome	1
2	Completed	Treatment	Agnogenic Myeloid Metaplasia	2
2	Completed	Treatment	Alopecia Areata (AA)	1
2	Completed	Treatment	Multiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed Multiple Myeloma	1
2	Completed	Treatment	Plaque Psoriasis	1
2	Completed	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
2	Completed	Treatment	Rheumatoid Arthritis	1
2	Completed	Treatment	Thalassemia Major (TM)	1
2	Enrolling by Invitation	Treatment	Breastcancer / Colorectal Cancers / Lung Cancer Non-Small Cell / Malignant Neoplasm of Pancreas	1
2	Not Yet Recruiting	Prevention	Atypical Ductal Hyperplasia / Atypical Lobular Hyperplasia / Ductal Carcinoma In Situ / Lobular Carcinoma in Situ (LCIS)	1
2	Recruiting	Other	Leukemias	1
2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia	2
2	Recruiting	Treatment	Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-Abelson (BCR-ABL) 1 Negative / Chronic Neutrophilic Leukemia	1
2	Recruiting	Treatment	B-cell Acute Lymphoblastic Leukemia	1
2	Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Other Diseases of Blood and Blood-Forming Organs	1
2	Recruiting	Treatment	Essential Thrombocythemia (ET)	1
2	Recruiting	Treatment	Graft Versus Host Disease (GVHD)	2
2	Recruiting	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2	Recruiting	Treatment	Inflammatory carcinoma of the breast	1
2	Recruiting	Treatment	Leukemia, Adult T-Cell / T Cell Leukemia, Adult / T Cell Leukemia, HTLV I Associated	1
2	Recruiting	Treatment	Leukemias	2
2	Recruiting	Treatment	Malignant Lymphomas	1
2	Recruiting	Treatment	Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Refractory Diffuse Large B-Cell Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma	1
2	Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (PET-MF) / Post-Polycythemia Vera-Myelofibrosis / Post-Polycythemia Vera-Myelofibrosis (PPV-MF) / Primary Myelofibrosis / Primary Myelofibrosis (PMF)	1
2	Recruiting	Treatment	Post Essential Thrombocythemia-myelofibrosis / Post Polycythemia Vera-myelofibrosis / Primary Myelofibrosis	1
2	Recruiting	Treatment	Primary Myelofibrosis / Secondary Myelofibrosis	1
2	Recruiting	Treatment	Recurrent Classical Hodgkin Lymphoma	1
2	Recruiting	Treatment	Refractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors	1
2	Recruiting	Treatment	Vitiligo	1
2	Recruiting	Treatment	Moderate, refractory Atopic dermatitis	1
2	Terminated	Treatment	Cancer, Breast	1
2	Terminated	Treatment	Metastatic Hormone Refractory Prostate Cancer	1
2	Terminated	Treatment	Primary Myelofibrosis	1
2, 3	Recruiting	Treatment	Essential Thrombocythemia (ET)	1
3	Active Not Recruiting	Treatment	Pancreatic Adenocarcinoma Metastatic	1
3	Active Not Recruiting	Treatment	Polycythemia Vera (PV)	2
3	Active Not Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
3	Completed	Treatment	Agnogenic Myeloid Metaplasia	2
3	Completed	Treatment	Polycythemia Vera (PV)	1
3	Completed	Treatment	Primary Myelofibrosis (MF)	1
3	Not Yet Recruiting	Treatment	Graft Versus Host Disease (GVHD)	1
3	Recruiting	Treatment	Corticosteroid Refractory Acute Graft vs Host Disease	1
3	Recruiting	Treatment	Essential Thrombocythemia (ET) / Polycythemia Vera (PV)	1
3	Recruiting	Treatment	Polycythemia Vera (PV)	1
3	Terminated	Treatment	Early Myelofibrosis With High Molecular Risk Mutations	1
3	Terminated	Treatment	Metastatic Pancreatic Adenocarcinoma That is Recurrent	1
4	Completed	Treatment	Post Essential Thrombocythaemia Myelofibrosis (PET-MF) / Post Polycythaemia Myelofibrosis (PPV MF) / Primary Myelofibrosis (PMF)	1
4	No Longer Available	Not Available	Agnogenic Myeloid Metaplasia / Myelofibrosis (PMF) / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Myelofibrosis / Post Polycythemia Myelofibrosis (PPV MF) / Post-essential Thrombocythemia Myelofibrosis (PET-MF)	1
4	Recruiting	Treatment	Splenomegaly	1
Not Available	Available	Not Available	Erythrocytosis, Familial, 2	1
Not Available	Available	Not Available	Graft-versus-host Disease (GVHD)	1
Not Available	Recruiting	Supportive Care	Primary Myelofibrosis / Secondary Myelofibrosis	1
Not Available	Withdrawn	Treatment	Agnogenic Myeloid Metaplasia / MF	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Tablet	Oral	10 mg/1
Tablet	Oral	15 mg/1
Tablet	Oral	20 mg/1
Tablet	Oral	25 mg/1
Tablet	Oral	5 mg/1
Tablet	Oral	10 mg
Tablet	Oral	15 mg
Tablet	Oral	20 mg
Tablet	Oral	5 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US7598257	No	2007-12-24	2027-12-24	US
US8415362	No	2007-12-24	2027-12-24	US
US8722693	No	2008-06-12	2028-06-12	US
US8822481	No	2008-06-12	2028-06-12	US
US8829013	No	2008-06-12	2028-06-12	US
US9079912	No	2006-12-12	2026-12-12	US

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	Yes	ChemAxon
MDDR-like Rule	Yes	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

Not Available

Taxonomy

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

Pyrrolo[2,3-d]pyrimidine / Pyrimidine / Heteroaromatic compound / Pyrrole / Pyrazole / Azole / Azacycle / Nitrile / Carbonitrile / Organic nitrogen compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

pyrazoles, nitrile, pyrrolopyrimidine (CHEBI:66919 )

Targets

Details

1. Tyrosine-protein kinase JAK1

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: inhibitor

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
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. [PubMed:23514013 ]
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 ]

Details

2. Tyrosine-protein kinase JAK2

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: inhibitor

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 adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR)...
Gene Name:: JAK2
Uniprot ID:: O60674
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. [PubMed:23514013 ]
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 ]

Enzymes

Details

1. Cytochrome P450 3A4

Kind: Protein
Organism: Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:: CYP3A4
Uniprot ID:: P08684
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. [PubMed:23061804 ]

Drug created on May 13, 2013 12:21 / Updated on June 24, 2017 13:29

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Structure for DB08877 (Ruxolitinib)

Targets

References

References

Enzymes

References