Identification
NameRuxolitinib
Accession NumberDB08877
TypeSmall Molecule
GroupsApproved
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
Thumb
Synonyms
INCB424
External IDs INC-424 / INC424 / INCB 18424 / INCB-018424 / INCB-18424 / INCB018424
Product Ingredients
IngredientUNIICASInChI KeyDetails
Ruxolitinib Phosphate436LRU32H5 1092939-17-7JFMWPOCYMYGEDM-XFULWGLBSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JakafiTablet5 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet20 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet10 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet25 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet15 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakaviTablet10 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet10 mgOralNovartis2015-04-15Not applicableCanada
JakaviTablet20 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet5 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 mgOralNovartis2012-07-19Not applicableCanada
JakaviTablet10 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet5 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet20 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet20 mgOralNovartis2012-07-19Not applicableCanada
JakaviTablet10 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet5 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet5 mgOralNovartis2012-07-19Not applicableCanada
JakaviTablet20 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII82S8X8XX8H
CAS number941678-49-5
WeightAverage: 306.365
Monoisotopic: 306.159294606
Chemical FormulaC17H18N6
InChI KeyHFNKQEVNSGCOJV-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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Tyrosine-protein kinase JAK1Proteinyes
inhibitor
HumanP23458 details
Tyrosine-protein kinase JAK2Proteinyes
inhibitor
HumanO60674 details
Related Articles
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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololRuxolitinib may increase the bradycardic activities of Acebutolol.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ruxolitinib.Approved
AmiodaroneThe serum concentration of Ruxolitinib can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Ruxolitinib can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Ruxolitinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololRuxolitinib may increase the bradycardic activities of Atenolol.Approved
AtomoxetineThe metabolism of Ruxolitinib can be decreased when combined with Atomoxetine.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Ruxolitinib.Investigational
BendroflumethiazideRuxolitinib may increase the bradycardic activities of Bendroflumethiazide.Approved
BeractantRuxolitinib may increase the bradycardic activities of Beractant.Approved
BetaxololRuxolitinib may increase the bradycardic activities of Betaxolol.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Ruxolitinib.Approved, Investigational
BexaroteneThe serum concentration of Ruxolitinib can be decreased when it is combined with Bexarotene.Approved, Investigational
BisoprololRuxolitinib may increase the bradycardic activities of Bisoprolol.Approved
BoceprevirThe serum concentration of Ruxolitinib can be increased when it is combined with Boceprevir.Approved, Investigational
BortezomibThe metabolism of Ruxolitinib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Ruxolitinib can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ruxolitinib.Approved
CalfactantRuxolitinib may increase the bradycardic activities of Calfactant.Approved
CarbamazepineThe metabolism of Ruxolitinib can be increased when combined with Carbamazepine.Approved, Investigational
CarteololRuxolitinib may increase the bradycardic activities of Carteolol.Approved
CarvedilolRuxolitinib may increase the bradycardic activities of Carvedilol.Approved, Investigational
CeritinibThe serum concentration of Ruxolitinib can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe serum concentration of Ruxolitinib can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Ruxolitinib can be decreased when combined with Clemastine.Approved
ClonidineRuxolitinib may increase the bradycardic activities of Clonidine.Approved
ClotrimazoleThe metabolism of Ruxolitinib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Clozapine.Approved
CobicistatThe serum concentration of Ruxolitinib can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Ruxolitinib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibRuxolitinib may increase the bradycardic activities of Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ruxolitinib.Approved, Investigational
CyclosporineThe metabolism of Ruxolitinib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Ruxolitinib can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Ruxolitinib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Ruxolitinib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Ruxolitinib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Ruxolitinib can be decreased when combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Ruxolitinib.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ruxolitinib.Approved
DexamethasoneThe serum concentration of Ruxolitinib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DexmedetomidineRuxolitinib may increase the bradycardic activities of Dexmedetomidine.Approved, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ruxolitinib.Approved
DigoxinRuxolitinib may increase the bradycardic activities of Digoxin.Approved
DihydroergotamineThe metabolism of Ruxolitinib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemRuxolitinib may increase the bradycardic activities of Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ruxolitinib.Approved, Investigational
DonepezilRuxolitinib may increase the bradycardic activities of Donepezil.Approved
DoxycyclineThe metabolism of Ruxolitinib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneRuxolitinib may increase the bradycardic activities of Dronedarone.Approved
EfavirenzThe serum concentration of Ruxolitinib can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Ruxolitinib can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Ruxolitinib can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Ruxolitinib can be decreased when it is combined with Eslicarbazepine acetate.Approved
EsmololRuxolitinib may increase the bradycardic activities of Esmolol.Approved
EtravirineThe serum concentration of Ruxolitinib can be decreased when it is combined with Etravirine.Approved
FingolimodRuxolitinib may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FluconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Fluconazole.Approved
FluvoxamineThe metabolism of Ruxolitinib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Ruxolitinib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Ruxolitinib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Ruxolitinib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Ruxolitinib can be increased when it is combined with Fusidic Acid.Approved
G17DTThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with G17DT.Investigational
GalantamineRuxolitinib may increase the bradycardic activities of Galantamine.Approved
GuanfacineRuxolitinib may increase the bradycardic activities of Guanfacine.Approved, Investigational
IdelalisibThe serum concentration of Ruxolitinib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Ruxolitinib can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Ruxolitinib can be increased when it is combined with Indinavir.Approved
INGN 201The risk or severity of adverse effects can be increased when Ruxolitinib is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Ruxolitinib is combined with INGN 225.Investigational
IsavuconazoniumThe metabolism of Ruxolitinib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Ruxolitinib can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvabradineRuxolitinib may increase the bradycardic activities of Ivabradine.Approved
IvacaftorThe serum concentration of Ruxolitinib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolRuxolitinib may increase the bradycardic activities of Labetalol.Approved
LanreotideRuxolitinib may increase the bradycardic activities of Lanreotide.Approved
LeflunomideThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Leflunomide.Approved, Investigational
LevobunololRuxolitinib may increase the bradycardic activities of Levobunolol.Approved
LopinavirThe serum concentration of Ruxolitinib can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Ruxolitinib can be decreased when combined with Lovastatin.Approved, Investigational
LucinactantRuxolitinib may increase the bradycardic activities of Lucinactant.Approved
LuliconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Ruxolitinib can be increased when combined with Lumacaftor.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Ruxolitinib.Withdrawn
MethyldopaRuxolitinib may increase the bradycardic activities of Methyldopa.Approved
MetipranololRuxolitinib may increase the bradycardic activities of Metipranolol.Approved
MetoprololRuxolitinib may increase the bradycardic activities of Metoprolol.Approved, Investigational
MifepristoneThe serum concentration of Ruxolitinib can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Ruxolitinib can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Ruxolitinib can be decreased when it is combined with Modafinil.Approved, Investigational
NadololRuxolitinib may increase the bradycardic activities of Nadolol.Approved
NafcillinThe serum concentration of Ruxolitinib can be decreased when it is combined with Nafcillin.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Natalizumab.Approved, Investigational
NebivololRuxolitinib may increase the bradycardic activities of Nebivolol.Approved, Investigational
NefazodoneThe serum concentration of Ruxolitinib can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ruxolitinib can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Ruxolitinib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Ruxolitinib can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Ruxolitinib can be decreased when combined with Nilotinib.Approved, Investigational
OctreotideRuxolitinib may increase the bradycardic activities of Octreotide.Approved, Investigational
OlaparibThe metabolism of Ruxolitinib can be decreased when combined with Olaparib.Approved
OleandrinAnvirzel may decrease the cardiotoxic activities of Ruxolitinib.Experimental
OsimertinibThe serum concentration of Ruxolitinib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Ruxolitinib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ruxolitinib.Approved, Vet Approved
PalbociclibThe serum concentration of Ruxolitinib can be increased when it is combined with Palbociclib.Approved
PasireotideRuxolitinib may increase the bradycardic activities of Pasireotide.Approved
PenbutololRuxolitinib may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentobarbitalThe metabolism of Ruxolitinib can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Ruxolitinib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Ruxolitinib can be increased when combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Ruxolitinib.Approved, Investigational
PindololRuxolitinib may increase the bradycardic activities of Pindolol.Approved
Poractant alfaRuxolitinib may increase the bradycardic activities of Poractant alfa.Approved
PosaconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Ruxolitinib can be increased when combined with Primidone.Approved, Vet Approved
PropafenoneRuxolitinib may increase the bradycardic activities of Propafenone.Approved
PropranololRuxolitinib may increase the bradycardic activities of Propranolol.Approved, Investigational
RanolazineThe metabolism of Ruxolitinib can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Ruxolitinib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Ruxolitinib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Ruxolitinib can be increased when combined with Rifapentine.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with CDX-110.Investigational
RitonavirThe serum concentration of Ruxolitinib can be increased when it is combined with Ritonavir.Approved, Investigational
RivastigmineRuxolitinib may increase the bradycardic activities of Rivastigmine.Approved, Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Ruxolitinib.Approved
SaquinavirThe serum concentration of Ruxolitinib can be increased when it is combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Ruxolitinib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Ruxolitinib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Ruxolitinib can be increased when it is combined with Simeprevir.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Ruxolitinib.Approved
SotalolRuxolitinib may increase the bradycardic activities of Sotalol.Approved
SRP 299The risk or severity of adverse effects can be increased when Ruxolitinib is combined with SRP 299.Investigational
St. John's WortThe serum concentration of Ruxolitinib can be decreased when it is combined with St. John&#39;s Wort.Nutraceutical
StiripentolThe serum concentration of Ruxolitinib can be increased when it is combined with Stiripentol.Approved
SufentanilRuxolitinib may increase the bradycardic activities of Sufentanil.Approved, Investigational
SulfisoxazoleThe metabolism of Ruxolitinib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Ruxolitinib.Approved, Investigational
TelaprevirThe serum concentration of Ruxolitinib can be increased when it is combined with Telaprevir.Withdrawn
TelithromycinThe serum concentration of Ruxolitinib can be increased when it is combined with Telithromycin.Approved
TiclopidineThe metabolism of Ruxolitinib can be decreased when combined with Ticlopidine.Approved
TimololRuxolitinib may increase the bradycardic activities of Timolol.Approved
TizanidineRuxolitinib may increase the bradycardic activities of Tizanidine.Approved
TocilizumabThe serum concentration of Ruxolitinib can be decreased when it is combined with Tocilizumab.Approved
TofacitinibRuxolitinib may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ruxolitinib.Approved, Investigational
VenlafaxineThe metabolism of Ruxolitinib can be decreased when combined with Venlafaxine.Approved
VerapamilRuxolitinib may increase the bradycardic activities of Verapamil.Approved
VoriconazoleThe serum concentration of Ruxolitinib can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Ruxolitinib can be decreased when combined with Ziprasidone.Approved
Food Interactions
  • Take without regards to meals
References
Synthesis ReferenceNot Available
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
ATC CodesL01XE18 — Ruxolitinib
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (399 KB)
MSDSDownload (210 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentHemophagocytic Syndrome (HPS)1
0WithdrawnTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
1Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia2
1Active Not RecruitingTreatmentChronic Phase Chronic Myeloid Leukemia1
1Active Not RecruitingTreatmentIdiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis1
1Active Not RecruitingTreatmentLeukemias1
1Active Not RecruitingTreatmentMetastatic Cancers / Pancreatic Cancer Metastatic1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Childhood Solid Tumor, Protocol Specific1
1Not Yet RecruitingTreatmentBreast Carcinoma Metastatic in the Bone / Estrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma1
1RecruitingHealth Services ResearchAgnogenic Myeloid Metaplasia1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAgnogenic Myeloid Metaplasia1
1RecruitingTreatmentAgnogenic Myeloid Metaplasia / Polycythemia Vera (PV)1
1RecruitingTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
1WithdrawnSupportive CareAcute myeloid leukaemia (in remission) / Primary Myelofibrosis / Primary Myelofibrosis, Prefibrotic Stage / Secondary Acute Myeloid Leukemia / Secondary Myelofibrosis1
1, 2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
1, 2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia / Polycythemia Vera (PV) / Thrombocytosis1
1, 2Active Not RecruitingTreatmentBlood Platelet Disorders / Bone Marrow Diseases / Disorders, Blood Coagulation / Essential Thrombocythemia (ET) / Hematologic Diseases / Hemorrhagic Disorders / Myeloproliferative Disorders / Primary Myelofibrosis / Thrombocytosis1
1, 2Active Not RecruitingTreatmentChronic Myeloid Leukemia (CML)1
1, 2Active Not RecruitingTreatmentLung Cancers1
1, 2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC) / Recurrent Breast Cancer1
1, 2Active Not RecruitingTreatmentMyelomonocytic Leukemia1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2CompletedTreatmentLeukemias1
1, 2Not Yet RecruitingTreatmentChronic Myeloid Leukemia (CML)1
1, 2Not Yet RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2RecruitingTreatmentAccelerated phase chronic myologenic leukemia / Blastic Phase Chronic Myeloid Leukemia / Chronic Phase Chronic Myeloid Leukemia / Philadelphia Positive Acute Lymphoblastic Leukemia / Resistant to Tyrosine Kinase Inhibitor Therapy1
1, 2RecruitingTreatmentAgnogenic Myeloid Metaplasia2
1, 2RecruitingTreatmentCancer, Advanced1
1, 2RecruitingTreatmentCarcinoma, Breast / HER-2 Positive Breast Cancer / Metastatic Breast Cancer (MBC)1
1, 2RecruitingTreatmentFallopian 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 Cancer1
1, 2RecruitingTreatmentLeukemias1
1, 2RecruitingTreatmentLeukemias / Myeloproliferative Diseases1
1, 2RecruitingTreatmentMyeloproliferative Disorders / Primary Myelofibrosis1
1, 2RecruitingTreatmentMyeloproliferative Neoplasms1
1, 2RecruitingTreatmentPMF / Post-ET MF / Post-PV MF / Primary Myelofibrosis / Secondary Myelofibrosis / SMF1
2Active Not RecruitingSupportive CareAnemias / Primary Myelofibrosis / Secondary Myelofibrosis1
2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
2Active Not RecruitingTreatmentCancer Cachexia1
2Active Not RecruitingTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV)1
2Active Not RecruitingTreatmentEstrogen-receptor Positive Invasive Metastatic Breast Cancer1
2Active Not RecruitingTreatmentLymphoma, Hodgkins1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentMetastatic Colorectal Cancers1
2Active Not RecruitingTreatmentMyeloproliferative Diseases2
2Active Not RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
2Active Not RecruitingTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
2Active Not RecruitingTreatmentPost-Essential Thrombocythemia (ET) MF / Post-Polycythemia Vera (PV) MF / Primary Myelofibrosis (MF)1
2Active Not RecruitingTreatmentPrimary mediastinal large B-cell lymphomas / Relapsed or Refractory Hodgkin Lymphoma1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myeloid Leukaemias (AML) / Chronic Myelogenous Leukemia (CML) / Myelodysplastic Syndrome1
2CompletedTreatmentAgnogenic Myeloid Metaplasia2
2CompletedTreatmentAlopecia Areata (AA)1
2CompletedTreatmentMultiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed Multiple Myeloma1
2CompletedTreatmentPlaque Psoriasis1
2CompletedTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentThalassemia Major (TM)1
2Enrolling by InvitationTreatmentBreastcancer / Colorectal Cancers / Lung Cancer Non-Small Cell / Malignant Neoplasm of Pancreas1
2Not Yet RecruitingPreventionAtypical Ductal Hyperplasia / Atypical Lobular Hyperplasia / Ductal Carcinoma In Situ / Lobular Carcinoma in Situ (LCIS)1
2RecruitingOtherLeukemias1
2RecruitingTreatmentAgnogenic Myeloid Metaplasia2
2RecruitingTreatmentAtypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-Abelson (BCR-ABL) 1 Negative / Chronic Neutrophilic Leukemia1
2RecruitingTreatmentB-cell Acute Lymphoblastic Leukemia1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Other Diseases of Blood and Blood-Forming Organs1
2RecruitingTreatmentEssential Thrombocythemia (ET)1
2RecruitingTreatmentGraft Versus Host Disease (GVHD)2
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2RecruitingTreatmentInflammatory carcinoma of the breast1
2RecruitingTreatmentLeukemia, Adult T-Cell / T Cell Leukemia, Adult / T Cell Leukemia, HTLV I Associated1
2RecruitingTreatmentLeukemias2
2RecruitingTreatmentMalignant Lymphomas1
2RecruitingTreatmentPeripheral 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 Lymphoma1
2RecruitingTreatmentPost 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
2RecruitingTreatmentPost Essential Thrombocythemia-myelofibrosis / Post Polycythemia Vera-myelofibrosis / Primary Myelofibrosis1
2RecruitingTreatmentPrimary Myelofibrosis / Secondary Myelofibrosis1
2RecruitingTreatmentRecurrent Classical Hodgkin Lymphoma1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentVitiligo1
2RecruitingTreatmentModerate, refractory Atopic dermatitis1
2TerminatedTreatmentAdvanced or Metastatic HER2-negative Breast Cancer1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer1
2TerminatedTreatmentPrimary Myelofibrosis1
2, 3RecruitingTreatmentEssential Thrombocythemia (ET)1
3Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
3Active Not RecruitingTreatmentPolycythemia Vera (PV)2
3Active Not RecruitingTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
3CompletedTreatmentAgnogenic Myeloid Metaplasia2
3CompletedTreatmentPolycythemia Vera (PV)1
3CompletedTreatmentPrimary Myelofibrosis (MF)1
3RecruitingTreatmentCorticosteroid Refractory Acute Graft vs Host Disease1
3RecruitingTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV)1
3RecruitingTreatmentGraft Versus Host Disease (GVHD)1
3RecruitingTreatmentPolycythemia Vera (PV)1
3TerminatedTreatmentEarly Myelofibrosis With High Molecular Risk Mutations1
3TerminatedTreatmentMetastatic Pancreatic Adenocarcinoma That is Recurrent1
4CompletedTreatmentPost Essential Thrombocythaemia Myelofibrosis (PET-MF) / Post Polycythaemia Myelofibrosis (PPV MF) / Primary Myelofibrosis (PMF)1
4No Longer AvailableNot AvailableAgnogenic Myeloid Metaplasia / Myelofibrosis (PMF) / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Myelofibrosis / Post Polycythemia Myelofibrosis (PPV MF) / Post-essential Thrombocythemia Myelofibrosis (PET-MF)1
4RecruitingTreatmentSplenomegaly1
Not AvailableAvailableNot AvailableErythrocytosis, Familial, 21
Not AvailableAvailableNot AvailableGraft-versus-host Disease (GVHD)1
Not AvailableRecruitingSupportive CarePrimary Myelofibrosis / Secondary Myelofibrosis1
Not AvailableWithdrawnTreatmentAgnogenic Myeloid Metaplasia / MF1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral10 mg/1
TabletOral15 mg/1
TabletOral20 mg/1
TabletOral25 mg/1
TabletOral5 mg/1
TabletOral10 mg
TabletOral15 mg
TabletOral20 mg
TabletOral5 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7598257 No2007-12-242027-12-24Us
US8415362 No2007-12-242027-12-24Us
US8722693 No2008-06-122028-06-12Us
US8822481 No2008-06-122028-06-12Us
US8829013 No2008-06-122028-06-12Us
US9079912 No2006-12-122026-12-12Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySoluble in aqueous buffers across a pH of 1-8FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.116 mg/mLALOGPS
logP2.94ALOGPS
logP2.48ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)13.89ChemAxon
pKa (Strongest Basic)5.51ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.18 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.01 m3·mol-1ChemAxon
Polarizability33.04 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9673
Caco-2 permeable-0.5198
P-glycoprotein substrateNon-substrate0.7838
P-glycoprotein inhibitor INon-inhibitor0.8228
P-glycoprotein inhibitor IIInhibitor0.7092
Renal organic cation transporterNon-inhibitor0.5098
CYP450 2C9 substrateNon-substrate0.8394
CYP450 2D6 substrateNon-substrate0.8075
CYP450 3A4 substrateNon-substrate0.6535
CYP450 1A2 substrateInhibitor0.6426
CYP450 2C9 inhibitorNon-inhibitor0.7731
CYP450 2D6 inhibitorNon-inhibitor0.9208
CYP450 2C19 inhibitorNon-inhibitor0.6689
CYP450 3A4 inhibitorNon-inhibitor0.6655
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5753
Ames testAMES toxic0.5681
CarcinogenicityNon-carcinogens0.9308
BiodegradationNot ready biodegradable0.9917
Rat acute toxicity2.5724 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.633
hERG inhibition (predictor II)Non-inhibitor0.8772
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrrolopyrimidines
Sub ClassPyrrolo[2,3-d]pyrimidines
Direct ParentPyrrolo[2,3-d]pyrimidines
Alternative ParentsPyrimidines and pyrimidine derivatives / Pyrroles / Pyrazoles / Heteroaromatic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
SubstituentsPyrrolo[2,3-d]pyrimidine / Pyrimidine / Heteroaromatic compound / Pyrrole / Pyrazole / Azole / Azacycle / Nitrile / Carbonitrile / Organic nitrogen compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorspyrazoles, nitrile, pyrrolopyrimidine (CHEBI:66919 )

Targets

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
  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 ]
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
  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 ]

Enzymes

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
  1. 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 July 21, 2017 17:50