Identification

Name
Ruxolitinib
Accession Number
DB08877  (DB06164)
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
Not Available
External IDs
INC-424 / INC424 / INCB 18424 / INCB-018424 / INCB-18424 / INCB018424 / INCB18424 / INCB424
Product Ingredients
IngredientUNIICASInChI Key
Ruxolitinib phosphate436LRU32H51092939-17-7JFMWPOCYMYGEDM-XFULWGLBSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JakafiTablet5.0 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet15.0 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet25.0 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet10.0 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakafiTablet20.0 mg/1OralIncyte Corporation2011-11-16Not applicableUs
JakaviTablet10 mgOralNovartis2015-04-15Not applicableCanada
JakaviTablet5 mgOralNovartis2012-07-19Not applicableCanada
JakaviTablet10 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet20 mgOralNovartis Europharm Limited2012-08-23Not applicableEu
JakaviTablet15 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[C@H](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).

Associated Conditions
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
DrugInteraction
(R)-warfarinThe metabolism of Ruxolitinib can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Ruxolitinib.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Ruxolitinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ruxolitinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ruxolitinib.
5-androstenedioneThe metabolism of Ruxolitinib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Ruxolitinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Ruxolitinib.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Ruxolitinib is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbacavirAbacavir may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
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 RecruitingHealth Services ResearchAgnogenic Myeloid Metaplasia1
1Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
1Active Not RecruitingTreatmentChronic Phase Chronic Myeloid Leukemia1
1Active Not RecruitingTreatmentLeukemias1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentAgnogenic Myeloid Metaplasia3
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Childhood Solid Tumor, Protocol Specific1
1Not Yet RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / All / ALL, Childhood1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
1RecruitingTreatmentAgnogenic Myeloid Metaplasia / Polycythemia Vera (PV)1
1RecruitingTreatmentAgnogenic Myeloid Metaplasia / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
1RecruitingTreatmentBreast 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
1RecruitingTreatmentGlioblastomas / Gliomas1
1RecruitingTreatmentIdiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis1
1RecruitingTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMultiple Myeloma (MM)1
1RecruitingTreatmentMyelofibroses1
1TerminatedTreatmentMalignant Neoplasm of Pancreas / Metastatic Cancers / Pancreatic Cancer Metastatic / Tumors, Solid1
1WithdrawnSupportive CareAcute myeloid leukaemia (in remission) / Primary Myelofibrosis / Primary Myelofibrosis, Prefibrotic Stage / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelofibrosis1
1, 2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
1, 2Active Not RecruitingTreatmentCancer, Advanced / Solid Tumors and Hematologic Malignancy / Tumors, Solid1
1, 2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC) / Recurrent Breast Cancer1
1, 2Active Not RecruitingTreatmentMyelomonocytic Leukemia1
1, 2Active Not RecruitingTreatmentMyeloproliferative Disorders / Primary Myelofibrosis1
1, 2Active Not RecruitingTreatmentMyeloproliferative Neoplasms1
1, 2CompletedTreatmentAgnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms) / Polycythemia Vera (PV) / Thrombocytosis1
1, 2CompletedTreatmentBlood Platelet Disorders / Bone Marrow Diseases / Disorders, Blood Coagulation / Essential Thrombocythemia (ET) / Hematologic Diseases / Hemorrhagic Disorders / Myeloproliferative Disorders / Primary Myelofibrosis / Thrombocytosis1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2CompletedTreatmentChronic Myeloid Leukemia (CML)1
1, 2CompletedTreatmentLeukemias1
1, 2CompletedTreatmentLung Cancers1
1, 2Not Yet RecruitingTreatmentAcute T Cell Leukemia1
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 Metaplasia1
1, 2RecruitingTreatmentAgnogenic Myeloid Metaplasia / Leukemia, Myelocytic, Acute / Myelodysplastic Syndromes (MDS) / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Myelodysplastic/Myeloproliferative Neoplasms1
1, 2RecruitingTreatmentAcute, recurrent Myeloid Leukemia / Blasts More Than 20 Percent of Bone Marrow Nucleated Cells / Blasts More Than 20 Percent of Peripheral Blood White Cells / Leukemias / Myelodysplastic/Myeloproliferative Neoplasms / Myeloproliferative Disorders / Refractory Acute Myeloid Leukemia1
1, 2RecruitingTreatmentCancer, Advanced / Solid Tumors and Hematologic Malignancy / Tumors, Solid1
1, 2RecruitingTreatmentCarcinoma, Breast / HER-2 Positive Breast Cancer / Metastatic Breast Cancer (MBC)1
1, 2RecruitingTreatmentChronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission / Leukemias / Minimal Residual Disease / Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia1
1, 2RecruitingTreatmentChronic Myeloid Leukemia (CML)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 Fallopian Tube Cancer AJCC v7 / Stage III Ovarian Cancer / Stage III Ovarian Cancer AJCC v6 and v7 / Stage III Primary Peritoneal Cancer / Stage III Primary Peritoneal Cancer AJCC v7 / Stage IIIA Fallopian Tube Cancer / Stage IIIA Fallopian Tube Cancer AJCC v7 / Stage IIIA Ovarian Cancer / Stage IIIA Ovarian Cancer AJCC v6 and v7 / Stage IIIA Primary Peritoneal Cancer / Stage IIIA Primary Peritoneal Cancer AJCC v7 / Stage IIIB Fallopian Tube Cancer / Stage IIIB Fallopian Tube Cancer AJCC v7 / Stage IIIB Ovarian Cancer / Stage IIIB Ovarian Cancer AJCC v6 and v7 / Stage IIIB Primary Peritoneal Cancer / Stage IIIB Primary Peritoneal Cancer AJCC v7 / Stage IIIC Fallopian Tube Cancer / Stage IIIC Fallopian Tube Cancer AJCC v7 / Stage IIIC Ovarian Cancer / Stage IIIC Ovarian Cancer AJCC v6 and v7 / Stage IIIC Primary Peritoneal Cancer / Stage IIIC Primary Peritoneal Cancer AJCC v7 / Stage IV Fallopian Tube Cancer / Stage IV Fallopian Tube Cancer AJCC v6 and v7 / Stage IV Ovarian Cancer / Stage IV Ovarian Cancer AJCC v6 and v7 / Stage IV Primary Peritoneal Cancer / Stage IV Primary Peritoneal Cancer AJCC v71
1, 2RecruitingTreatmentGraft Versus Host Disease, Acute1
1, 2RecruitingTreatmentLymphoma, Hodgkins1
1, 2RecruitingTreatmentPMF / Post-ET MF / Post-PV MF / Primary Myelofibrosis / Secondary Myelofibrosis / SMF1
1, 2RecruitingTreatmentSecondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Disorder1
2Active Not RecruitingTreatmentAgnogenic Myeloid Metaplasia1
2Active Not RecruitingTreatmentCancer Cachexia1
2Active Not RecruitingTreatmentEstrogen-receptor Positive Invasive Metastatic Breast Cancer1
2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)1
2Active Not RecruitingTreatmentLeukemias1
2Active Not RecruitingTreatmentLichen Planus (LP)1
2Active Not RecruitingTreatmentMPN (Myeloproliferative Neoplasms) / Post Essential Thrombocythemia-myelofibrosis / Post Polycythemia Vera-myelofibrosis / Primary Myelofibrosis1
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentPeripheral 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
2Active Not RecruitingTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
2Active Not RecruitingTreatmentPost 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
2CompletedSupportive CareAnemias / Primary Myelofibrosis / Secondary Myelofibrosis1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Chronic myelogenous leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentAgnogenic Myeloid Metaplasia2
2CompletedTreatmentAlopecia Areata (AA)1
2CompletedTreatmentAtopic Dermatitis (AD)1
2CompletedTreatmentEssential Thrombocythemia (ET) / MPN (Myeloproliferative Neoplasms) / Polycythemia Vera (PV)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentLymphoma, Hodgkins1
2CompletedTreatmentMalignant Neoplasm of Pancreas / Pancreatic Adenocarcinoma Metastatic1
2CompletedTreatmentMultiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed Multiple Myeloma1
2CompletedTreatmentMyeloproliferative Disorders2
2CompletedTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
2CompletedTreatmentPost-Essential Thrombocythemia (ET) MF / Post-Polycythemia Vera (PV) MF / Primary Myelofibrosis (MF)1
2CompletedTreatmentPrimary mediastinal large B-cell lymphomas / Relapsed or Refractory Hodgkin Lymphoma1
2CompletedTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
2CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentThalassemia Major (TM)1
2Enrolling by InvitationTreatmentBreastcancer / Cancer, Breast / Colorectal Cancer (CRC) / Colorectal Cancers / CRC (Colorectal Cancer) / Lung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers / Malignant Neoplasm of Pancreas / NSCLC (Non-small Cell Lung Carcinoma)1
2Not Yet RecruitingPreventionAcute GvHD1
2Not Yet RecruitingTreatmentChronic Myeloid Leukemia, Chronic Phase / Chronic Phase Chronic Myeloid Leukemia1
2Not Yet RecruitingTreatmentChronic Myelomonocytic Leukemia / Leukemias1
2Not Yet RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
2Not Yet RecruitingTreatmentOther Cancer1
2RecruitingPreventionAtypical Ductal Hyperplasia / Atypical Lobular Hyperplasia / Ductal Carcinoma In Situ / Lobular Carcinoma in Situ (LCIS)1
2RecruitingTreatmentALL (Acute Lymphoblastic Leukemia) / B-cell Acute Lymphoblastic Leukemia / Leukemias1
2RecruitingTreatmentAcute myeloid leukaemia (in remission) / Allogeneic Stem Cell Transplantation / Leukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentAgnogenic Myeloid Metaplasia2
2RecruitingTreatmentAgnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms)2
2RecruitingTreatmentAtypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-Abelson (BCR-ABL) 1 Negative / Chronic Neutrophilic Leukemia1
2RecruitingTreatmentBone Marrow Fibrosis1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Other Diseases of Blood and Blood-Forming Organs / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive1
2RecruitingTreatmentEssential Thrombocythemia (ET) / MPN (Myeloproliferative Neoplasms)1
2RecruitingTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV)1
2RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2RecruitingTreatmentGraft Versus Host Disease (GVHD) / JNS Kinase / Topical Administration1
2RecruitingTreatmentGraft-versus-host-disease (GVHD)1
2RecruitingTreatmentInflammatory carcinoma of the breast1
2RecruitingTreatmentLeukemia, Adult T-Cell / T Cell Leukemia, Adult / T Cell Leukemia, HTLV I Associated1
2RecruitingTreatmentLeukemias1
2RecruitingTreatmentLeukemias / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Myelofibrosis Transformation in Essential Thrombocythemia / Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase / Primary Myelofibrosis1
2RecruitingTreatmentMalignant Lymphomas1
2RecruitingTreatmentMyelofibrosis (MF)1
2RecruitingTreatmentPolycythemia Vera (PV)1
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 Cancer / Cancer, Breast1
2TerminatedTreatmentCRC (Colorectal Cancer) / Metastatic Colorectal Cancers1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / NSCLC (Non-small Cell Lung Carcinoma)1
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer / Prostate Cancer1
2TerminatedTreatmentPrimary Myelofibrosis1
2, 3Active Not RecruitingTreatmentEssential Thrombocythemia (ET)1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma1
3Active Not RecruitingTreatmentPolycythemia Vera (PV)1
3Active Not RecruitingTreatmentPost Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis1
3CompletedTreatmentAgnogenic Myeloid Metaplasia1
3CompletedTreatmentAgnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms)1
3CompletedTreatmentAgnogenic Myeloid Metaplasia / Myelofibrosis (PMF) / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Myelofibrosis / Post Polycythemia Myelofibrosis (PPV MF) / Post-essential Thrombocythemia Myelofibrosis (PET-MF)1
3CompletedTreatmentEarly Myelofibrosis With High Molecular Risk Mutations1
3CompletedTreatmentPolycythemia Vera (PV)2
3CompletedTreatmentPrimary Myelofibrosis (MF)1
3RecruitingTreatmentCorticosteroid Refractory Acute Graft vs Host Disease1
3RecruitingTreatmentGraft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)1
3RecruitingTreatmentPolycythemia Vera (PV)1
3TerminatedTreatmentMalignant Neoplasm of Pancreas / Metastatic Pancreatic Adenocarcinoma That is Recurrent1
3TerminatedTreatmentMalignant Neoplasm of Pancreas / Pancreatic Adenocarcinoma Metastatic1
4CompletedTreatmentPost Essential Thrombocythaemia Myelofibrosis (PET-MF) / Post Polycythaemia Myelofibrosis (PPV MF) / Primary Myelofibrosis (PMF)1
4RecruitingTreatmentSplenomegaly1
Not AvailableAvailableNot AvailableGraft-versus-host Disease (GVHD)1
Not AvailableNo Longer AvailableNot AvailableErythrocytosis, Familial, 21
Not AvailableRecruitingSupportive CarePrimary Myelofibrosis / Secondary Myelofibrosis1
Not AvailableRecruitingTreatmentProstate Cancer1
Not AvailableWithdrawnTreatmentAgnogenic Myeloid Metaplasia / MF1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10.0 mg/1
TabletOral15.0 mg/1
TabletOral20.0 mg/1
TabletOral25.0 mg/1
TabletOral5.0 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 13, 2018 08:04