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
Thumb
Synonyms
  • INCB424
External IDs
INC-424 / INC424 / INCB 18424 / INCB-018424 / INCB-18424 / INCB018424
Product Ingredients
IngredientUNIICASInChI Key
Ruxolitinib Phosphate436LRU32H51092939-17-7JFMWPOCYMYGEDM-XFULWGLBSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JakafiTablet25 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet15 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet5 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet20 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet10 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakaviTablet20 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet5 mgOralNovartis2012-07-19Not applicableCanada
JakaviTablet10 mgOralNovartis2015-04-15Not applicableCanada
JakaviTablet10 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
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.

TargetActionsOrganism
ATyrosine-protein kinase JAK1
inhibitor
Human
ATyrosine-protein kinase JAK2
inhibitor
Human
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
DrugInteractionDrug group
AcebutololRuxolitinib may increase the bradycardic activities of Acebutolol.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ruxolitinib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Ruxolitinib.Experimental
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 vaccine 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
BisoprololRuxolitinib may increase the bradycardic activities of Bisoprolol.Approved
BoceprevirThe serum concentration of Ruxolitinib can be increased when it is combined with Boceprevir.Approved, Withdrawn
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
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Ruxolitinib.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
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Ruxolitinib.Approved
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
CymarinCymarin may decrease the cardiotoxic activities of Ruxolitinib.Experimental
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
DexmedetomidineRuxolitinib may increase the bradycardic activities of Dexmedetomidine.Approved, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ruxolitinib.Approved, Investigational
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
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
EsmololRuxolitinib may increase the bradycardic activities of Esmolol.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 therapeutic efficacy of G17DT can be decreased when used in combination with Ruxolitinib.Investigational
GalantamineRuxolitinib may increase the bradycardic activities of Galantamine.Approved
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Ruxolitinib.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Ruxolitinib.Experimental
GuanfacineRuxolitinib may increase the bradycardic activities of Guanfacine.Approved, Investigational
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 therapeutic efficacy of INGN 201 can be decreased when used in combination with Ruxolitinib.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Ruxolitinib.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
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Ruxolitinib.Experimental
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, Investigational
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.Investigational, Withdrawn
MethyldopaRuxolitinib may increase the bradycardic activities of Methyldopa.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Ruxolitinib.Experimental
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
NadololRuxolitinib may increase the bradycardic activities of Nadolol.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
OleandrinOleandrin may decrease the cardiotoxic activities of Ruxolitinib.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Ruxolitinib.Experimental
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
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Ruxolitinib.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Ruxolitinib.Approved
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 therapeutic efficacy of Rindopepimut can be decreased when used in combination with Ruxolitinib.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
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Ruxolitinib.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with 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 therapeutic efficacy of SRP 299 can be decreased when used in combination with Ruxolitinib.Investigational
St. John's WortThe serum concentration of Ruxolitinib can be decreased when it is combined with St. John&#39;s Wort.Investigational, 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
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Ruxolitinib.Investigational
TelaprevirThe serum concentration of Ruxolitinib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Ruxolitinib can be increased when it is combined with Telithromycin.Approved
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Ruxolitinib.Investigational
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
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Ruxolitinib.Approved
ZiprasidoneThe metabolism of Ruxolitinib can be decreased when combined with Ziprasidone.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Ruxolitinib.Approved
Food Interactions
  • Take without regards to meals

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
ChEBI
66919
ChEMBL
CHEMBL1789941
PharmGKB
PA166123386
HET
RXT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ruxolitinib
ATC Codes
L01XE18 — Ruxolitinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4u5j
FDA label
Download (399 KB)
MSDS
Download (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 RecruitingTreatmentMetastatic Breast Cancer (MBC) / Recurrent Breast Cancer1
1, 2Active Not RecruitingTreatmentMyelomonocytic Leukemia1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2CompletedTreatmentLeukemias1
1, 2CompletedTreatmentLung Cancers1
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 Disorders1
1, 2RecruitingTreatmentMyeloproliferative Disorders / Primary Myelofibrosis1
1, 2RecruitingTreatmentMyeloproliferative Neoplasms1
1, 2RecruitingTreatmentPMF / Post-ET MF / Post-PV MF / Primary Myelofibrosis / Secondary Myelofibrosis / SMF1
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 Disorders2
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
2CompletedSupportive CareAnemias / Primary Myelofibrosis / Secondary Myelofibrosis1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Myelogenous Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / 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
2CompletedTreatmentPrimary mediastinal large B-cell lymphomas / Relapsed or Refractory Hodgkin Lymphoma1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentThalassemia Major (TM)1
2Enrolling by InvitationTreatmentBreastcancer / Colorectal Cancers / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Pancreas1
2Not Yet RecruitingPreventionAtypical Ductal Hyperplasia / Atypical Lobular Hyperplasia / Ductal Carcinoma In Situ / Lobular Carcinoma in Situ (LCIS)1
2Not Yet RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2RecruitingOtherLeukemias1
2RecruitingTreatmentAcute myeloid leukaemia (in remission) / Allogeneic Stem Cell Transplantation / Leukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentAgnogenic Myeloid Metaplasia3
2RecruitingTreatmentAtopic Dermatitis (AD)1
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 Organs / Small Lymphocytic Lymphoma (SLL)1
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
2RecruitingTreatmentMyelofibrosis (MF)1
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
2TerminatedTreatmentAdvanced or Metastatic HER2-negative Breast Cancer1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer1
2TerminatedTreatmentPrimary Myelofibrosis1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
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 AvailableRecruitingTreatmentProstate Cancer1
Not AvailableWithdrawnTreatmentAgnogenic Myeloid Metaplasia / MF1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not 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
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7598257No2007-12-242027-12-24Us
US8822481No2008-06-122028-06-12Us
US8829013No2008-06-122028-06-12Us
US9079912No2006-12-122026-12-12Us
US8415362No2007-12-242027-12-24Us
US8722693No2008-06-122028-06-12Us
US9662335No2006-12-122026-12-12Us

Properties

State
Solid
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
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot 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

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
Uniprot Name
Tyrosine-protein kinase JAK1
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 adaptiv...
Gene Name
JAK2
Uniprot ID
O60674
Uniprot Name
Tyrosine-protein kinase JAK2
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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 November 14, 2017 08:12