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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H18N6
Molecular Weight 306.3657
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RUXOLITINIB

SMILES

C1CCC(C1)[C@@]([H])(CC#N)n2cc(cn2)-c3c-4ccnc4[nH]cn3

InChI

InChIKey=HFNKQEVNSGCOJV-OAHLLOKOSA-N
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

HIDE SMILES / InChI

Molecular Formula C17H18N6
Molecular Weight 306.3657
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2012_jakavi_151723-eng.php; https://www.ncbi.nlm.nih.gov/pubmed/19385672; http://www.businesswire.com/news/home/20160406005608/en/Incyte-Acquires-Rights-Lilly-Develop-Commercialize-Ruxolitinib

Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, for plaque psoriasis, and for alopecia areata. Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. Ruxolitinib is a Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies. In a mouse model of JAK2V617F-positive MPN, ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (eg, TNF-α, IL-6). Ruxolitinib was initially synthesized at Incyte Corporation that acquired the rights to develop and commercialize the drug in US. Incyte amended its Collaboration and License Agreement with Novartis, granting Novartis exclusive research, development and commercialization rights for ruxolitinib outside the U.S.

CNS Activity

Curator's Comment:: Ruxolitinib and its metabolites crossed the blood brain barrier (<10% of plasma concentrations) and placental barrier of rats.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P23458
Gene ID: 3716.0
Gene Symbol: JAK1
Target Organism: Homo sapiens (Human)
3.3 nM [IC50]
Target ID: O60674
Gene ID: 3717.0
Gene Symbol: JAK2
Target Organism: Homo sapiens (Human)
2.8 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
JAKAFI

Approved Use

Indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis and polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea

Launch Date

1.32140158E12
Primary
JAKAFI

Approved Use

Indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis and polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea

Launch Date

1.32140158E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
333 nM
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1100 nM
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5300 nM
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
613 nM
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
562 nM
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3180 nM × h
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4350 nM × h
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
21500 nM × h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2160 nM × h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2190 nM × h
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.3 h
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.8 h
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.28 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.98 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.96 h
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RUXOLITINIB unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3.3%
RUXOLITINIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 62 years
n = 5
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 62 years
Sex: M+F
Population Size: 5
Sources: Page: 202192Orig1s000MedR.pdf - p.24
DLT: Thrombocytopenia...
Disc. AE: Thrombocytopenia...
Other AEs: Thrombocytopenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 20%)
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (grade 3, 40%)
Other AEs:
Thrombocytopenia (grade 3, 60%)
Sources: Page: 202192Orig1s000MedR.pdf - p.24
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Other AEs: Asthenia, Fever...
Other AEs:
Asthenia (grade 3, 2%)
Fever (grade 3, 0.7%)
Fatigue (grade 3, 1.3%)
Anxiety (grade 3, 1.3%)
Insomnia (grade 3, 1.3%)
Pneumonia (0.7%)
Fever (1.3%)
Anemia (2%)
Asthenia (2%)
Systemic inflammatory response syndrome (1.3%)
Anxiety (1.3%)
Constitutional syndrome (1.3%)
Insomnia (1.3%)
Sources:
25 mg 2 times / day multiple, oral
MTD
Dose: 25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 25 mg, 2 times / day
Sources:
unhealthy, Median age 67 years
n = 47
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 67 years
Sex: M+F
Population Size: 47
Sources:
Other AEs: Thrombocytopenia...
25 mg 2 times / day multiple, oral
MTD
Dose: 25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 25 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 67 years
n = 47
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 67 years
Sex: M+F
Population Size: 47
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Other AEs: Thrombocytopenia...
Other AEs:
Thrombocytopenia (grade 4, 6%)
Sources: Page: 202192Orig1s000MedR.pdf - p.24
100 mg 1 times / day multiple, oral
MTD
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, Median age 71 years
n = 6
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 71 years
Sex: M+F
Population Size: 6
Sources:
Other AEs: Thrombocytopenia...
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 75 years
n = 3
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 75 years
Sex: M+F
Population Size: 3
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Other AEs: Thrombocytopenia...
Other AEs:
Thrombocytopenia (grade 4, 33%)
Sources: Page: 202192Orig1s000MedR.pdf - p.24
20 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 155
Other AEs: Thrombocytopenia...
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Disc. AE: Thrombocytopenia, Neutropenia...
Other AEs: Anemia, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (1%)
Neutropenia (1%)
Anemia (1%)
Diarrhea (1%)
Septic shock (1%)
Subdural hematoma (1%)
Hemorrhage retroperitoneal (1%)
Other AEs:
Anemia (grade 3, 10.3%)
Diarrhea (grade 3, 1.9%)
Epistaxis (grade 3, 0.6%)
Dizziness (grade 3, 0.6%)
Pneumonia (grade 3, 3.2%)
Thrombocytopenia (grade 4, 1.3%)
Anemia (grade 4, 5.2%)
Pneumonia (grade 4, 1.9%)
Thrombocytopenia (34%)
Anemia (31%)
Headache (15%)
Dizziness (15%)
Confusion (14%)
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia grade 3, 40%
Disc. AE
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 62 years
n = 5
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 62 years
Sex: M+F
Population Size: 5
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Thrombocytopenia grade 3, 60%
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 62 years
n = 5
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 62 years
Sex: M+F
Population Size: 5
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Thrombocytopenia grade 4, 20%
DLT
50 mg 2 times / day multiple, oral
Dose: 50 mg, 2 times / day
Route: oral
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 62 years
n = 5
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 62 years
Sex: M+F
Population Size: 5
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Pneumonia 0.7%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Anxiety 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Constitutional syndrome 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Fever 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Insomnia 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Systemic inflammatory response syndrome 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Anemia 2%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Asthenia 2%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Fever grade 3, 0.7%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Anxiety grade 3, 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Fatigue grade 3, 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Insomnia grade 3, 1.3%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Asthenia grade 3, 2%
72 mg 1 times / day multiple, oral (mean)
Dose: 72 mg, 1 times / day
Route: oral
Route: multiple
Dose: 72 mg, 1 times / day
Sources:
unhealthy, Median age 65 years
n = 153
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 65 years
Sex: M+F
Population Size: 153
Sources:
Thrombocytopenia grade 3, 23%
25 mg 2 times / day multiple, oral
MTD
Dose: 25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 25 mg, 2 times / day
Sources:
unhealthy, Median age 67 years
n = 47
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 67 years
Sex: M+F
Population Size: 47
Sources:
Thrombocytopenia grade 4, 6%
25 mg 2 times / day multiple, oral
MTD
Dose: 25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 25 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 67 years
n = 47
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 67 years
Sex: M+F
Population Size: 47
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Thrombocytopenia grade 3, 33%
100 mg 1 times / day multiple, oral
MTD
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
unhealthy, Median age 71 years
n = 6
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 71 years
Sex: M+F
Population Size: 6
Sources:
Thrombocytopenia grade 4, 33%
200 mg 1 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.24
unhealthy, Median age 75 years
n = 3
Health Status: unhealthy
Condition: myelofibrosis
Age Group: Median age 75 years
Sex: M+F
Population Size: 3
Sources: Page: 202192Orig1s000MedR.pdf - p.24
Thrombocytopenia grade 3, 7.1%
20 mg 2 times / day multiple, oral
Recommended
unhealthy, adult
n = 155
Anemia 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Diarrhea 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Hemorrhage retroperitoneal 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Neutropenia 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Septic shock 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Subdural hematoma 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Thrombocytopenia 1%
Disc. AE
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Confusion 14%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Dizziness 15%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Headache 15%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Anemia 31%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Thrombocytopenia 34%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Dizziness grade 3, 0.6%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Epistaxis grade 3, 0.6%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Diarrhea grade 3, 1.9%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Anemia grade 3, 10.3%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Pneumonia grade 3, 3.2%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Thrombocytopenia grade 4, 1.3%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Pneumonia grade 4, 1.9%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
Anemia grade 4, 5.2%
20 mg 2 times / day multiple, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
unhealthy, adult
n = 155
Health Status: unhealthy
Condition: myelofibrosis
Age Group: adult
Sex: M+F
Population Size: 155
Sources: Page: 202192Orig1s000MedR.pdf - p.67-70
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes [IC50 19.3 uM]
yes [IC50 20.5 uM]
yes [IC50 21 uM]
yes [IC50 48 uM]
yes [IC50 6.5 uM]
yes [IC50 9.1 uM]
yes [IC50 9.8 uM]
yes [IC50 >25 uM]
yes [IC50 >25 uM]
yes [IC50 >25 uM]
yes [IC50 >25 uM]
yes [IC50 >25 uM]
yes [IC50 >25 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: 3A4 is the predominant human CYP isozyme responsible for the metabolism of ruxolitinib. Systemic co-administration of oral ketoconazole, a potent CYP3A4 inhibitor, resulted in a 91% increase of plasma AUC, whereas erythromycin, a moderate CYP3A4 inhibitor, caused a 27% increase in exposure.
Page: -
minor
minor
minor
minor
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Myelofibrosis: an update on current pharmacotherapy and future directions.
2013 May
Patents

Sample Use Guides

20 mg given orally twice daily for patients with a platelet count greater than 200 X 10^9/L, and 15 mg twice daily for patients with a platelet count between 100 X 10^9/L and 200 X 10^9/L
Route of Administration: Oral
Ba/F3 cells and HEL cells were used to evaluate the effects of INCB018424 on viability and JAK-mediated signaling. Cells were treated with increasing concentrations of INCB018424 in the concentration range of 3-3000 nM for 2.5 hours, and extracts from these cells were subjected to immunoblot analysis for phosphorylated or total forms of proteins associated with the JAK/STAT signaling pathway..
Substance Class Chemical
Created
by admin
on Sat Jun 26 12:03:09 UTC 2021
Edited
by admin
on Sat Jun 26 12:03:09 UTC 2021
Record UNII
82S8X8XX8H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RUXOLITINIB
DASH   INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
RUXOLITINIB [VANDF]
Common Name English
INCB018424
Code English
INC424
Code English
RUXOLITINIB [USAN]
Common Name English
INCB-018424
Code English
RUXOLITINIB [MI]
Common Name English
INC-424
Code English
(3R)-3-CYCLOPENTYL-3-(4-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)PYRAZOL-1-YL)PROPANENITRILE
Systematic Name English
1H-PYRAZOLE-1-PROPANENITRILE, .BETA.-CYCLOPENTYL-4-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YL)-, (.BETA.R)-
Common Name English
RUXOLITINIB [WHO-DD]
Common Name English
INCB-18424
Code English
RUXOLITINIB [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
NDF-RT N0000175605
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
FDA ORPHAN DRUG 302310
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
LIVERTOX 866
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
WHO-ATC L01XE18
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
FDA ORPHAN DRUG 529116
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
FDA ORPHAN DRUG 400613
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
NCI_THESAURUS C1967
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
EU-Orphan Drug EU/3/14/1244
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
FDA ORPHAN DRUG 542716
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
WHO-VATC QL01XE18
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
Code System Code Type Description
EPA CompTox
941678-49-5
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
RXCUI
1193326
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL1789941
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
FDA UNII
82S8X8XX8H
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
NCI_THESAURUS
C77888
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
EVMPD
SUB32273
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
DRUG CENTRAL
4190
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
MERCK INDEX
M9710
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY Merck Index
PUBCHEM
25126798
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
MESH
C540383
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
LACTMED
Ruxolitinib
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
DRUG BANK
DB08877
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
WIKIPEDIA
RUXOLITINIB
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
HSDB
8259
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
CAS
941678-49-5
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
IUPHAR
5688
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
INN
9287
Created by admin on Sat Jun 26 12:03:11 UTC 2021 , Edited by admin on Sat Jun 26 12:03:11 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
EXCRETED UNCHANGED
FECAL; URINE
TRANSPORTER -> NON-INHIBITOR
GREATER THAN 100 MICROMOLAR
IC50
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC