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Properties

Spectra

Taxonomy

Ruxolitinib

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

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

Similar Structures

Synonyms

Ruxolitinib

External IDs

INC-424 / INC424 / INCB 18424 / INCB-018424 / INCB-18424 / INCB018424 / INCB18424 / INCB424

Product Ingredients

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

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Jakafi	Tablet	15.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	10.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	25.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	5.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	20.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakavi	Tablet	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet	10 mg	Oral	Novartis	2015-04-15	Not applicable
Jakavi	Tablet	10 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet	20 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable
Jakavi	Tablet	5 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable

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.

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

Absorption

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

Volume of distribution

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

Protein binding

97% protein bound, primarily to albumin.

Metabolism

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

Route of elimination

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

Half life

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

Clearance

15 mg, healthy subject = 18.7 L/h.

Toxicity

Thrombocytopenia was the dose-limiting toxicity.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of Ruxolitinib can be decreased when combined with (R)-warfarin.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Ruxolitinib.
2-Methoxyethanol	The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Ruxolitinib.
3,5-diiodothyropropionic acid	The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ruxolitinib.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Ruxolitinib.
5-androstenedione	The metabolism of Ruxolitinib can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide B	The metabolism of Ruxolitinib can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine	The metabolism of 6-O-benzylguanine can be decreased when combined with Ruxolitinib.
7-ethyl-10-hydroxycamptothecin	The metabolism of Ruxolitinib can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
9-(N-methyl-L-isoleucine)-cyclosporin A	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.

Food Interactions

Take without regards to meals

References

General References

Cervantes F, Martinez-Trillos A: Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013 May;14(7):873-84. doi: 10.1517/14656566.2013.783019. Epub 2013 Mar 21. [PubMed:23514013]
Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [PubMed:23061804]

External Links

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

Phase	Status	Purpose	Conditions	Count
0	Recruiting	Treatment	Hemophagocytic Syndrome (HPS)	1
0	Withdrawn	Treatment	Head and Neck Squamous Cell Carcinoma (HNSCC)	1
1	Active Not Recruiting	Health Services Research	Agnogenic Myeloid Metaplasia	1
1	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
1	Active Not Recruiting	Treatment	Idiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis	1
1	Active Not Recruiting	Treatment	Leukemias	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Treatment	Agnogenic Myeloid Metaplasia	3
1	Completed	Treatment	Chronic Myeloproliferative Disorders / Leukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Unspecified Childhood Solid Tumor, Protocol Specific	1
1	Completed	Treatment	Chronic Phase Chronic Myeloid Leukemia	1
1	Not Yet Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL) / All / ALL, Childhood	1
1	Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL)	1
1	Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia	1
1	Recruiting	Treatment	Agnogenic Myeloid Metaplasia / Polycythemia Vera (PV)	1
1	Recruiting	Treatment	Agnogenic Myeloid Metaplasia / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
1	Recruiting	Treatment	Breast Carcinoma Metastatic in the Bone / Estrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor Negative / Recurrent Breast Carcinoma / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma	1
1	Recruiting	Treatment	Glioblastomas / Gliomas	1
1	Recruiting	Treatment	Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)	1
1	Recruiting	Treatment	Multiple Myeloma (MM)	1
1	Recruiting	Treatment	Myelofibroses	1
1	Terminated	Treatment	Malignant Neoplasm of Pancreas / Metastatic Cancers / Pancreatic Cancer Metastatic / Tumors, Solid	1
1	Withdrawn	Supportive Care	Acute myeloid leukaemia (in remission) / Primary Myelofibrosis / Primary Myelofibrosis, Prefibrotic Stage / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelofibrosis	1
1, 2	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
1, 2	Active Not Recruiting	Treatment	Cancer, Advanced / Solid Tumors and Hematologic Malignancy / Tumors, Solid	1
1, 2	Active Not Recruiting	Treatment	Metastatic Breast Cancer (MBC) / Recurrent Breast Cancer	1
1, 2	Active Not Recruiting	Treatment	Myelomonocytic Leukemia	1
1, 2	Active Not Recruiting	Treatment	Myeloproliferative Disorders / Primary Myelofibrosis	1
1, 2	Active Not Recruiting	Treatment	Myeloproliferative Neoplasms	1
1, 2	Completed	Treatment	Agnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms) / Polycythemia Vera (PV) / Thrombocytosis	1
1, 2	Completed	Treatment	Blood Platelet Disorders / Bone Marrow Diseases / Disorders, Blood Coagulation / Essential Thrombocythemia (ET) / Hematologic Diseases / Hemorrhagic Disorders / Myeloproliferative Disorders / Primary Myelofibrosis / Thrombocytosis	1
1, 2	Completed	Treatment	Chronic Lymphocytic Leukaemia (CLL)	1
1, 2	Completed	Treatment	Chronic Myeloid Leukemia (CML)	1
1, 2	Completed	Treatment	Leukemias	1
1, 2	Completed	Treatment	Lung Cancers	1
1, 2	Not Yet Recruiting	Treatment	Acute T Cell Leukemia	1
1, 2	Not Yet Recruiting	Treatment	Leukemia, Lymphocytic, Chronic, B-Cell	1
1, 2	Recruiting	Treatment	Accelerated phase chronic myologenic leukemia / Blastic Phase Chronic Myeloid Leukemia / Chronic Phase Chronic Myeloid Leukemia / Philadelphia Positive Acute Lymphoblastic Leukemia / Resistant to Tyrosine Kinase Inhibitor Therapy	1
1, 2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
1, 2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia / Leukemia, Myelocytic, Acute / Myelodysplastic Syndromes (MDS) / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Myelodysplastic/Myeloproliferative Neoplasms	1
1, 2	Recruiting	Treatment	Acute, 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 Leukemia	1
1, 2	Recruiting	Treatment	Cancer, Advanced / Solid Tumors and Hematologic Malignancy / Tumors, Solid	1
1, 2	Recruiting	Treatment	Carcinoma, Breast / HER-2 Positive Breast Cancer / Metastatic Breast Cancer (MBC)	1
1, 2	Recruiting	Treatment	Chronic 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 Leukemia	1
1, 2	Recruiting	Treatment	Chronic Myeloid Leukemia (CML)	1
1, 2	Recruiting	Treatment	Fallopian Tube Carcinosarcoma / Fallopian Tube Clear Cell Adenocarcinoma / Fallopian Tube Endometrioid Adenocarcinoma / Fallopian Tube Serous Neoplasm / High Grade Ovarian Serous Adenocarcinoma / Ovarian Carcinosarcoma / Ovarian Clear Cell Adenocarcinoma / Ovarian Endometrioid Adenocarcinoma / Primary Peritoneal Serous Adenocarcinoma / Stage III Fallopian Tube Cancer / Stage III 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 v7	1
1, 2	Recruiting	Treatment	Graft Versus Host Disease, Acute	1
1, 2	Recruiting	Treatment	Lymphohistiocytosis, Hemophagocytic	1
1, 2	Recruiting	Treatment	Lymphoma, Hodgkins	1
1, 2	Recruiting	Treatment	Multiple Myeloma (MM)	1
1, 2	Recruiting	Treatment	PMF / Post-ET MF / Post-PV MF / Primary Myelofibrosis / Secondary Myelofibrosis / SMF	1
1, 2	Recruiting	Treatment	Secondary Acute Myelogenous Leukemia Evolving From Myeloproliferative Disorder	1
2	Active Not Recruiting	Treatment	Agnogenic Myeloid Metaplasia	1
2	Active Not Recruiting	Treatment	Cancer Cachexia	1
2	Active Not Recruiting	Treatment	Estrogen-receptor Positive Invasive Metastatic Breast Cancer	1
2	Active Not Recruiting	Treatment	Graft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)	1
2	Active Not Recruiting	Treatment	Leukemias	1
2	Active Not Recruiting	Treatment	Metastatic Cancers	1
2	Active Not Recruiting	Treatment	Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma	1
2	Active Not Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
2	Active Not Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (PET-MF) / Post-Polycythemia Vera-Myelofibrosis / Post-Polycythemia Vera-Myelofibrosis (PPV-MF) / Primary Myelofibrosis / Primary Myelofibrosis (PMF)	1
2	Active Not Recruiting	Treatment	Vitiligo	1
2	Completed	Supportive Care	Anemias / Primary Myelofibrosis / Secondary Myelofibrosis	1
2	Completed	Treatment	Acute Lymphocytic Leukemia (ALL) / Chronic Chronic myelogenous leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome	1
2	Completed	Treatment	Agnogenic Myeloid Metaplasia	2
2	Completed	Treatment	Alopecia Areata (AA)	1
2	Completed	Treatment	Atopic Dermatitis (AD)	1
2	Completed	Treatment	Essential Thrombocythemia (ET) / MPN (Myeloproliferative Neoplasms) / Polycythemia Vera (PV)	1
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Lymphoma, Hodgkins	1
2	Completed	Treatment	MPN (Myeloproliferative Neoplasms) / Post Essential Thrombocythemia-myelofibrosis / Post Polycythemia Vera-myelofibrosis / Primary Myelofibrosis	1
2	Completed	Treatment	Malignant Neoplasm of Pancreas / Pancreatic Adenocarcinoma Metastatic	1
2	Completed	Treatment	Multiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed Multiple Myeloma	1
2	Completed	Treatment	Myeloproliferative Disorders	2
2	Completed	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
2	Completed	Treatment	Post-Essential Thrombocythemia (ET) MF / Post-Polycythemia Vera (PV) MF / Primary Myelofibrosis (MF)	1
2	Completed	Treatment	Primary mediastinal large B-cell lymphomas / Relapsed or Refractory Hodgkin Lymphoma	1
2	Completed	Treatment	Psoriasis / Psoriasis Vulgaris (Plaque Psoriasis)	1
2	Completed	Treatment	Rheumatoid Arthritis	1
2	Completed	Treatment	Thalassemia Major (TM)	1
2	Enrolling by Invitation	Treatment	Breastcancer / 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
2	Not Yet Recruiting	Prevention	Acute GvHD	1
2	Not Yet Recruiting	Treatment	BCR-JAK2 Fusion Protein Expression / Blasts 20 Percent or Less of Peripheral Blood White Cells / Blasts More Than 5 Percent of Bone Marrow Nucleated Cells / Blasts More Than 5 Percent of Peripheral Blood White Cells / Blasts Under 20 Percent of Bone Marrow Nucleated Cells / Chronic Eosinophilic Leukemia, Not Otherwise Specified / Eosinophilia / Hepatomegaly / Hypereosinophilic Syndromes / JAK2 Gene Mutation / Splenomegaly / TEL-JAK2 Fusion Protein Expression	1
2	Not Yet Recruiting	Treatment	Chronic Myeloid Leukemia, Chronic Phase / Chronic Phase Chronic Myeloid Leukemia	1
2	Not Yet Recruiting	Treatment	Chronic Myelomonocytic Leukemia / Leukemias	1
2	Not Yet Recruiting	Treatment	Graft Versus Host Disease (GVHD)	1
2	Not Yet Recruiting	Treatment	Other Cancer	1
2	Recruiting	Prevention	Atypical Ductal Hyperplasia / Atypical Lobular Hyperplasia / Ductal Carcinoma In Situ / Lobular Carcinoma in Situ (LCIS)	1
2	Recruiting	Treatment	ALL (Acute Lymphoblastic Leukemia) / B-cell Acute Lymphoblastic Leukemia / Leukemias	1
2	Recruiting	Treatment	Acute myeloid leukaemia (in remission) / Allogeneic Stem Cell Transplantation / Leukemia Acute Myeloid Leukemia (AML)	1
2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia	2
2	Recruiting	Treatment	Agnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms)	2
2	Recruiting	Treatment	Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative / Atypical Chronic Myeloid Leukemia, Breakpoint Cluster Region-Abelson (BCR-ABL) 1 Negative / Chronic Neutrophilic Leukemia	1
2	Recruiting	Treatment	Bone Marrow Fibrosis	1
2	Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Other Diseases of Blood and Blood-Forming Organs / Small Lymphocytic Lymphoma (SLL)	1
2	Recruiting	Treatment	Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive	1
2	Recruiting	Treatment	Essential Thrombocythemia (ET) / MPN (Myeloproliferative Neoplasms)	1
2	Recruiting	Treatment	Essential Thrombocythemia (ET) / Polycythemia Vera (PV)	1
2	Recruiting	Treatment	Graft Versus Host Disease (GVHD)	1
2	Recruiting	Treatment	Graft Versus Host Disease (GVHD) / JNS Kinase / Topical Administration	1
2	Recruiting	Treatment	Graft-versus-host-disease (GVHD)	1
2	Recruiting	Treatment	Head and Neck Squamous Cell Carcinoma (HNSCC)	1
2	Recruiting	Treatment	Inflammatory carcinoma of the breast	1
2	Recruiting	Treatment	Leukemia, Adult T-Cell / T Cell Leukemia, Adult / T Cell Leukemia, HTLV I Associated	1
2	Recruiting	Treatment	Leukemias	1
2	Recruiting	Treatment	Leukemias / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Myelofibrosis Transformation in Essential Thrombocythemia / Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase / Primary Myelofibrosis	1
2	Recruiting	Treatment	Lichen Planus (LP)	1
2	Recruiting	Treatment	Malignant Lymphomas	1
2	Recruiting	Treatment	Myelofibrosis (MF)	1
2	Recruiting	Treatment	Polycythemia Vera (PV)	1
2	Recruiting	Treatment	Primary Myelofibrosis / Secondary Myelofibrosis	1
2	Recruiting	Treatment	Recurrent Classical Hodgkin Lymphoma	1
2	Recruiting	Treatment	Refractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors	1
2	Terminated	Treatment	Advanced or Metastatic HER2-negative Breast Cancer / Cancer, Breast	1
2	Terminated	Treatment	CRC (Colorectal Cancer) / Metastatic Colorectal Cancers	1
2	Terminated	Treatment	Cancer, Breast	1
2	Terminated	Treatment	Lung Cancer Non-Small Cell Cancer (NSCLC) / NSCLC (Non-small Cell Lung Carcinoma)	1
2	Terminated	Treatment	Metastatic Hormone Refractory Prostate Cancer / Prostate Cancer	1
2	Terminated	Treatment	Primary Myelofibrosis	1
2, 3	Active Not Recruiting	Treatment	Essential Thrombocythemia (ET)	1
2, 3	Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Lymphoma	1
3	Active Not Recruiting	Treatment	Polycythemia Vera (PV)	1
3	Active Not Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Vera Myelofibrosis / Primary Myelofibrosis	1
3	Completed	Treatment	Agnogenic Myeloid Metaplasia	1
3	Completed	Treatment	Agnogenic Myeloid Metaplasia / MPN (Myeloproliferative Neoplasms)	1
3	Completed	Treatment	Agnogenic Myeloid Metaplasia / Myelofibrosis (PMF) / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia Myelofibrosis / Post Polycythemia Myelofibrosis (PPV MF) / Post-essential Thrombocythemia Myelofibrosis (PET-MF)	1
3	Completed	Treatment	Early Myelofibrosis With High Molecular Risk Mutations	1
3	Completed	Treatment	Polycythemia Vera (PV)	2
3	Completed	Treatment	Primary Myelofibrosis (MF)	1
3	Recruiting	Treatment	Atopic Dermatitis (AD)	2
3	Recruiting	Treatment	Corticosteroid Refractory Acute Graft vs Host Disease	1
3	Recruiting	Treatment	Graft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)	1
3	Recruiting	Treatment	Polycythemia Vera (PV)	1
3	Terminated	Treatment	Malignant Neoplasm of Pancreas / Metastatic Pancreatic Adenocarcinoma That is Recurrent	1
3	Terminated	Treatment	Malignant Neoplasm of Pancreas / Pancreatic Adenocarcinoma Metastatic	1
4	Completed	Treatment	Post Essential Thrombocythaemia Myelofibrosis (PET-MF) / Post Polycythaemia Myelofibrosis (PPV MF) / Primary Myelofibrosis (PMF)	1
4	Recruiting	Treatment	Splenomegaly	1
Not Available	Available	Not Available	Graft-versus-host Disease (GVHD)	1
Not Available	No Longer Available	Not Available	Erythrocytosis, Familial, 2	1
Not Available	Recruiting	Supportive Care	Primary Myelofibrosis / Secondary Myelofibrosis	1
Not Available	Recruiting	Treatment	Prostate Cancer	1
Not Available	Withdrawn	Treatment	Agnogenic Myeloid Metaplasia / MF	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Tablet	Oral	10.0 mg/1
Tablet	Oral	15.0 mg/1
Tablet	Oral	20.0 mg/1
Tablet	Oral	25.0 mg/1
Tablet	Oral	5.0 mg/1
Tablet	Oral	10 mg
Tablet	Oral	15 mg
Tablet	Oral	20 mg
Tablet	Oral	5 mg

Prices

Not Available

Patents

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

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Soluble in aqueous buffers across a pH of 1-8	FDA label.

Predicted Properties

Property	Value	Source
Water Solubility	0.116 mg/mL	ALOGPS
logP	2.94	ALOGPS
logP	2.48	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	13.89	ChemAxon
pKa (Strongest Basic)	5.51	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	83.18 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	98.01 m³·mol^-1	ChemAxon
Polarizability	33.04 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	1.0
Blood Brain Barrier	+	0.9673
Caco-2 permeable	-	0.5198
P-glycoprotein substrate	Non-substrate	0.7838
P-glycoprotein inhibitor I	Non-inhibitor	0.8228
P-glycoprotein inhibitor II	Inhibitor	0.7092
Renal organic cation transporter	Non-inhibitor	0.5098
CYP450 2C9 substrate	Non-substrate	0.8394
CYP450 2D6 substrate	Non-substrate	0.8075
CYP450 3A4 substrate	Non-substrate	0.6535
CYP450 1A2 substrate	Inhibitor	0.6426
CYP450 2C9 inhibitor	Non-inhibitor	0.7731
CYP450 2D6 inhibitor	Non-inhibitor	0.9208
CYP450 2C19 inhibitor	Non-inhibitor	0.6689
CYP450 3A4 inhibitor	Non-inhibitor	0.6655
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.5753
Ames test	AMES toxic	0.5681
Carcinogenicity	Non-carcinogens	0.9308
Biodegradation	Not ready biodegradable	0.9917
Rat acute toxicity	2.5724 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.633
hERG inhibition (predictor II)	Non-inhibitor	0.8772

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

Spectra

Mass Spec (NIST)

Not Available

Spectra

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

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

Details1. Tyrosine-protein kinase JAK1

Kind: Protein
Organism: Humans
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

Cervantes F, Martinez-Trillos A: Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013 May;14(7):873-84. doi: 10.1517/14656566.2013.783019. Epub 2013 Mar 21. [PubMed:23514013]
Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [PubMed:23061804]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	12	N/A	N/A	22698084
IC 50 (nM)	2.8	N/A	N/A	22591402
IC 50 (nM)	3	N/A	N/A	21106455
IC 50 (nM)	6.85	N/A	N/A	23061660
Kd (nM)	0.036	N/A	N/A	22037378
Ki (nM)	0.1	N/A	N/A	22698084
Ki (nM)	0.24	N/A	N/A	23061660

Details2. Tyrosine-protein kinase JAK2

Kind: Protein
Organism: Humans
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

Cervantes F, Martinez-Trillos A: Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother. 2013 May;14(7):873-84. doi: 10.1517/14656566.2013.783019. Epub 2013 Mar 21. [PubMed:23514013]
Yang LP, Keating GM: Ruxolitinib: in the treatment of myelofibrosis. Drugs. 2012 Nov 12;72(16):2117-27. doi: 10.2165/11209340-000000000-00000. [PubMed:23061804]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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

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 February 18, 2019 20:23

Ruxolitinib

Identification

Structure for Ruxolitinib (DB08877)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

Enzymes

References