Ruxolitinib

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

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Ruxolitinib (DB08877)

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Synonyms

Not Available

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	5.0 mg/1	Oral	Incyte Corporation	2011-11-16	Not applicable
Jakafi	Tablet	15.0 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	10.0 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	10 mg	Oral	Novartis	2015-04-15	Not applicable
Jakavi	Tablet	5 mg	Oral	Novartis	2012-07-19	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	15 mg	Oral	Novartis Europharm Limited	2012-08-23	Not applicable

Categories

• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Immunosuppressive Agents
• Janus Kinases, antagonists & inhibitors
• Kinase Inhibitor
• Myelosuppressive Agents
• Protein Kinase Inhibitors
• Tyrosine Kinase Inhibitors

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

• Post Essential Thrombocythemia Myelofibrosis
• Post Polycythemia Vera Myelofibrosis
• High risk Myelofibrosis
• Intermediate risk Myelofibrosis
• Refractory Polycythemia vera

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	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

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
Acebutolol	Ruxolitinib may increase the bradycardic activities of Acebutolol.
Acetaminophen	Acetaminophen may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
Acetyl sulfisoxazole	The metabolism of Ruxolitinib can be decreased when combined with Acetyl sulfisoxazole.
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of Ruxolitinib.
Acetyldigoxin	Acetyldigoxin may decrease the cardiotoxic activities of Ruxolitinib.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Ruxolitinib which could result in a higher serum level.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Ruxolitinib.
Albendazole	The metabolism of Ruxolitinib can be decreased when combined with Albendazole.
Alclometasone	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Alclometasone.
Aldesleukin	The risk or severity of adverse effects can be increased when Ruxolitinib is combined with Aldesleukin.

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

• L01XE — Protein kinase inhibitors
• L01X — OTHER ANTINEOPLASTIC AGENTS
• L01 — ANTINEOPLASTIC AGENTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

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	Chronic Phase Chronic Myeloid Leukemia	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	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	Idiopathic Myelofibrosis / Post Essential Thrombocythemia Myelofibrosis / Post Polycythemia-Vera Myelofibrosis	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) / Acute, secondary Myeloid Leukemia / Primary Myelofibrosis / Primary Myelofibrosis, Prefibrotic Stage / 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	Chronic Myeloid Leukemia (CML)	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	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	Graft Versus Host Disease, Acute	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	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 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	Leukemias	1
1, 2	Recruiting	Treatment	Leukemias / Myeloproliferative Disorders	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	Essential Thrombocythemia (ET) / MPN (Myeloproliferative Neoplasms) / Polycythemia Vera (PV)	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	MPN (Myeloproliferative Neoplasms) / Post Essential Thrombocythemia-myelofibrosis / Post Polycythemia Vera-myelofibrosis / Primary Myelofibrosis	1
2	Active Not Recruiting	Treatment	Metastatic Cancers	1
2	Active Not Recruiting	Treatment	Myeloproliferative Disorders	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	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	Human Immunodeficiency Virus (HIV) Infections	1
2	Completed	Treatment	Lymphoma, Hodgkins	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	1
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	Treatment	Agnogenic Myeloid Metaplasia	1
2	Not Yet Recruiting	Treatment	Chronic Myeloid Leukemia, Chronic Phase / Chronic Phase Chronic Myeloid Leukemia	1
2	Not Yet Recruiting	Treatment	Graft-versus-host-disease (GVHD)	1
2	Not Yet Recruiting	Treatment	Head and Neck Squamous Cell Carcinoma (HNSCC)	1
2	Recruiting	Other	Leukemias	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	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	1
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	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	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	Malignant Lymphomas	1
2	Recruiting	Treatment	Myelofibrosis (MF)	1
2	Recruiting	Treatment	Polycythemia Vera (PV)	1
2	Recruiting	Treatment	Post Essential Thrombocythemia Myelofibrosis / Post-essential Thrombocythemia Myelofibrosis (PET-MF) / Post-Polycythemia Vera-Myelofibrosis / Post-Polycythemia Vera-Myelofibrosis (PPV-MF) / Primary Myelofibrosis / Primary Myelofibrosis (PMF)	1
2	Recruiting	Treatment	Primary Myelofibrosis / Secondary Myelofibrosis	1
2	Recruiting	Treatment	Recurrent Classical Hodgkin Lymphoma	1
2	Recruiting	Treatment	Refractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors	1
2	Recruiting	Treatment	Vitiligo	1
2	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	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	2007-12-24	2027-12-24
US8822481	No	2008-06-12	2028-06-12
US8829013	No	2008-06-12	2028-06-12
US9079912	No	2006-12-12	2026-12-12
US8415362	No	2007-12-24	2027-12-24
US8722693	No	2008-06-12	2028-06-12
US9662335	No	2006-12-12	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)

Drug created on May 13, 2013 12:21 / Updated on September 23, 2018 19:37