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Details

Stereochemistry ACHIRAL
Molecular Formula C27H36N6O3S
Molecular Weight 524.6803
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FEDRATINIB

SMILES

Cc1cnc(Nc2ccc(cc2)OCCN3CCCC3)[nH]c1=Nc4cccc(c4)S(=O)(=O)NC(C)(C)C

InChI

InChIKey=JOOXLOJCABQBSG-UHFFFAOYSA-N
InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)

HIDE SMILES / InChI

Molecular Formula C27H36N6O3S
Molecular Weight 524.6803
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/26181658 | http://adisinsight.springer.com/drugs/800027763

The clinical development of fedratinib was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.

CNS Activity

Curator's Comment:: The clinical development of fedratinib, a Janus kinase (JAK2) inhibitor, was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1804 ng/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2539 ng/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1760 ng/mL
680 mg single, oral
dose: 680 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FEDRATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
26870 ng × h/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
38712 ng × h/mL
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
17800 ng × h/mL
680 mg single, oral
dose: 680 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FEDRATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41 h
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
62.1 h
680 mg single, oral
dose: 680 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FEDRATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
8%
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2%
500 mg 1 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FEDRATINIB unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
8%
FEDRATINIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Other AEs: Anemia, Vomiting...
Other AEs:
Anemia (grade 3-4, 30%)
Vomiting (grade 3-4, 3.1%)
Asthenia (grade 3-4, 5%)
Blood creatinine increased (grade 3-4, 1%)
Thrombocytopenia (all grades, 47%)
Neutropenia (all grades, 23%)
Lipase increased (all grades, 35%)
Hyponatremia (all grades, 26%)
Amylase increased (all grades, 24%)
Thrombocytopenia (grade 3-4, 12%)
Neutropenia (grade 3-4, 5%)
Lipase increased (grade 3-4, 10%)
Hyponatremia (grade 3-4, 5%)
Amylase increased (grade 3-4, 2.1%)
Cardiac failure (all grades, 5%)
Sources:
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Other AEs: Diarrhea, Nausea...
Other AEs:
Diarrhea (all grades, 66%)
Nausea (all grades, 62%)
Anemia (all grades, 40%)
Vomiting (all grades, 39%)
Asthenia (all grades, 19%)
Muscle spasms (all grades, 12%)
Blood creatinine increased (all grades, 10%)
Pain in extremity (all grades, 10%)
Alanine aminotransferase increased (all grades, 9%)
Headache (all grades, 9%)
Weight increased (all grades, 9%)
Dizziness (all grades, 8%)
Bone pain (all grades, 8%)
Urinary tract infection (all grades, 6%)
Dysuria (all grades, 6%)
Aspartate aminotransferase increased (all grades, 5%)
Diarrhea (grade 3-4, 5%)
Sources:
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Disc. AE: Nausea, Cardiac failure...
Other AEs: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (>3)
Cardiac failure (grade 3-4, 3%)
Cardiac failure (grade 5, 1%)
Thrombocytopenia (2%)
Myocardial ischemia (2%)
Diarrhea (2%)
Blood creatinine increased (2%)
Other AEs:
Diarrhea (>3)
Nausea (>3)
Anemia (6%)
Diarrhea (3%)
Vomiting (3%)
Thrombocytopenia (2%)
Sources:
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Health Status: unhealthy
Age Group: 65 - 75 years
Sex: M+F
Sources:
Disc. AE: Anemia...
AEs leading to
discontinuation/dose reduction:
Anemia (1%)
Sources:
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Health Status: unhealthy
Age Group: 65 - 75 years
Sex: M+F
Sources:
Disc. AE: Cardiac disorders...
AEs leading to
discontinuation/dose reduction:
Cardiac disorders (grade 5, 2 patients)
Sources:
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Disc. AE: Thrombocytopenia, Neutropenia...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (6%)
Neutropenia (2%)
Vomiting (4%)
Blood creatinine increased (2%)
Diarrhea (2%)
Nausea (2%)
Amylase increased (1%)
Lipase increased (3%)
Fatigue (2%)
Diarrhea (all grades, 8%)
Diarrhea (grade 3-4, 3%)
Nausea (all grades, 6%)
Nausea (grade 3-4, 4%)
Vomiting (all grades, 11%)
Vomiting (grade 3-4, 7%)
Anemia (all grades, 18%)
Anemia (grade 3-4, 14%)
Thrombocytopenia (all grades, 7%)
Thrombocytopenia (grade 3-4, 6%)
Fatigue (all grades, 5%)
Fatigue (grade 3-4, 5%)
Sources:
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Disc. AE: Cardiac disorders...
AEs leading to
discontinuation/dose reduction:
Cardiac disorders (grade 5, 2 patients)
Sources:
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Disc. AE: Anemia, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Anemia (2%)
Diarrhea (2%)
Nausea (2%)
Amylase increased (1%)
Lipase increased (1%)
Vomiting (all grades, 10%)
Vomiting (grade 3-4, 3%)
Anemia (all grades, 8%)
Anemia (grade 3-4, 5%)
Thrombocytopenia (all grades, 3%)
Thrombocytopenia (grade 3-4, 2%)
Fatigue (all grades, 3%)
Fatigue (grade 3-4, 3%)
Sources:
800 mg single, oral
Highest studied dose
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
680 mg 1 times / day multiple, oral
MTD
Dose: 680 mg, 1 times / day
Route: oral
Route: multiple
Dose: 680 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
680 mg single, oral
MTD
Dose: 680 mg
Route: oral
Route: single
Dose: 680 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Other AEs: Gastrointestinal disorders...
Other AEs:
Gastrointestinal disorders
Sources:
800 mg 1 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
AEs

AEs

AESignificanceDosePopulation
Neutropenia all grades, 23%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Amylase increased all grades, 24%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Hyponatremia all grades, 26%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Lipase increased all grades, 35%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Thrombocytopenia all grades, 47%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Cardiac failure all grades, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Blood creatinine increased grade 3-4, 1%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Lipase increased grade 3-4, 10%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Thrombocytopenia grade 3-4, 12%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Amylase increased grade 3-4, 2.1%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Vomiting grade 3-4, 3.1%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Anemia grade 3-4, 30%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Asthenia grade 3-4, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Hyponatremia grade 3-4, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Neutropenia grade 3-4, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Blood creatinine increased all grades, 10%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Pain in extremity all grades, 10%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Muscle spasms all grades, 12%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Asthenia all grades, 19%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Vomiting all grades, 39%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Anemia all grades, 40%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Aspartate aminotransferase increased all grades, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Dysuria all grades, 6%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Urinary tract infection all grades, 6%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Nausea all grades, 62%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Diarrhea all grades, 66%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Bone pain all grades, 8%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Dizziness all grades, 8%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Alanine aminotransferase increased all grades, 9%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Headache all grades, 9%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Weight increased all grades, 9%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Diarrhea grade 3-4, 5%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Thrombocytopenia 2%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Blood creatinine increased 2%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Diarrhea 2%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Myocardial ischemia 2%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Thrombocytopenia 2%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Diarrhea 3%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Vomiting 3%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Anemia 6%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Diarrhea >3
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Nausea >3
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Nausea >3
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Cardiac failure grade 3-4, 3%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Cardiac failure grade 5, 1%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 27 - 86 years
Health Status: unhealthy
Age Group: 27 - 86 years
Sex: M+F
Sources:
Anemia 1%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Health Status: unhealthy
Age Group: 65 - 75 years
Sex: M+F
Sources:
Cardiac disorders grade 5, 2 patients
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Health Status: unhealthy
Age Group: 65 - 75 years
Sex: M+F
Sources:
Amylase increased 1%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Blood creatinine increased 2%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Diarrhea 2%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Fatigue 2%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Nausea 2%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Neutropenia 2%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Lipase increased 3%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Vomiting 4%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Thrombocytopenia 6%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Vomiting all grades, 11%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Anemia all grades, 18%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Fatigue all grades, 5%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Nausea all grades, 6%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Thrombocytopenia all grades, 7%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Diarrhea all grades, 8%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Anemia grade 3-4, 14%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Diarrhea grade 3-4, 3%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Nausea grade 3-4, 4%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Fatigue grade 3-4, 5%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Thrombocytopenia grade 3-4, 6%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Vomiting grade 3-4, 7%
Disc. AE
500 mg 1 times / day multiple, oral
Studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: multiple
Dose: 500 mg, 1 times / day
Sources:
unhealthy, 65 - 75 years
Cardiac disorders grade 5, 2 patients
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Amylase increased 1%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Lipase increased 1%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Anemia 2%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Diarrhea 2%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Nausea 2%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Vomiting all grades, 10%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Fatigue all grades, 3%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Thrombocytopenia all grades, 3%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Anemia all grades, 8%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Thrombocytopenia grade 3-4, 2%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Fatigue grade 3-4, 3%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Vomiting grade 3-4, 3%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Anemia grade 3-4, 5%
Disc. AE
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 65 years (range: 27 - 86 years)
Health Status: unhealthy
Age Group: 65 years (range: 27 - 86 years)
Sex: M+F
Sources:
Gastrointestinal disorders
680 mg single, oral
MTD
Dose: 680 mg
Route: oral
Route: single
Dose: 680 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes [IC50 0.227 uM]
yes [IC50 0.352 uM]
yes [IC50 0.78 uM]
yes [IC50 10.1 uM]
yes [IC50 100.8 uM]
yes [IC50 16.4 uM]
yes [IC50 20.2 uM]
yes (co-administration study)
Comment: fedratinib increased exposure of metoprolol by 2x
yes [IC50 29.9 uM]
yes [IC50 3 uM]
yes (co-administration study)
Comment: fedratinib increased exposure of midazolam by 4x
yes [IC50 52.2 uM]
yes [IC50 6.06 uM]
yes [IC50 9.51 uM]
yes
yes (co-administration study)
Comment: fedratinib increased exposure of omeprazole by 3x
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera.
2008 Apr
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.
2010 Dec 15
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.
2013 Sep 1
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
2014 Apr
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.
2015 Jun
Patents

Sample Use Guides

Fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF: once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. These benefits were accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism. Clinical development of fedratinib was subsequently discontinued.
Route of Administration: Oral
300 nM Fedratinib (SAR-302503, TG-101348) significantly inhibited JAK2V617F+ progenitor-derived colony formation
Substance Class Chemical
Created
by admin
on Sat Jun 26 10:16:07 UTC 2021
Edited
by admin
on Sat Jun 26 10:16:07 UTC 2021
Record UNII
6L1XP550I6
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FEDRATINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
FEDRATINIB [INN]
Common Name English
BENZENESULFONAMIDE, N-(1,1-DIMETHYLETHYL)-3-((5-METHYL-2-((4-(2-(1-PYRROLIDINYL)ETHOXY)PHENYL)AMINO)-4-PYRIMIDINYL)AMINO)-
Systematic Name English
FEDRATINIB [MI]
Common Name English
N-TERT-BUTYL-3-((5-METHYL-2-(4-(2-(PYRROLIDIN-1-YL)ETHOXY)ANILINO(PYRIMIDIN-4-YL)AMINO)BENZENESULFONAMIDE
Common Name English
N-TERT-BUTYL-3-(5-METHYL-2-(4-(2-PYRROLIDIN-1-YL-ETHOXY)-PHENYLAMINO)-PYRIMIDIN-4-YLAMINO)-BENZENESULFONAMIDE
Systematic Name English
SAR-302503
Code English
SAR302503
Code English
TG101348
Code English
TG-101348
Code English
FEDRATINIB [WHO-DD]
Common Name English
FEDRATINIB [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
NCI_THESAURUS C125450
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
Code System Code Type Description
WIKIPEDIA
TG101348
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
FDA UNII
6L1XP550I6
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
MERCK INDEX
M12160
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
ChEMBL
CHEMBL1287853
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
DRUG CENTRAL
5347
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
DRUG BANK
DB12500
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
INN
9707
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
EPA CompTox
936091-26-8
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
NCI_THESAURUS
C88293
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
CAS
936091-26-8
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
EVMPD
SUB126288
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
LACTMED
Fedratinib
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
PUBCHEM
16722836
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
RXCUI
2197490
Created by admin on Sat Jun 26 10:16:09 UTC 2021 , Edited by admin on Sat Jun 26 10:16:09 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0?20%), and FMO3 (0?33%) in vitro.
TARGET -> INHIBITOR
INHIBITOR
IC50
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
IC50
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0?20%), and FMO3 (0?33%) in vitro.
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
Patients being treated with fedratinib developed Wernicke?s encephalopathy (WE) (Sanofi, 2013), a neurological disorder linked to thiamine deficiency (Cook et al., 1998).
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Metabolized by CYP3A4 (0 to 70%), CYP2C19 (0?20%), and FMO3 (0?33%) in vitro.
TARGET -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Blood to Plasma Ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC STEADY-STATE

ONCE DAILY DOSE

ORAL ADMINISTRATION