U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H17F6N7O
Molecular Weight 473.375
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENASIDENIB

SMILES

CC(C)(O)CNC1=NC(NC2=CC(=NC=C2)C(F)(F)F)=NC(=N1)C3=NC(=CC=C3)C(F)(F)F

InChI

InChIKey=DYLUUSLLRIQKOE-UHFFFAOYSA-N
InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)

HIDE SMILES / InChI
Molecular Formula C19H17F6N7O
Molecular Weight 473.375
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.agios.com/patients-trials.php http://www.selleckchem.com/products/ag-221-enasidenib.html http://adisinsight.springer.com/drugs/800038591

Enasidenib, aslo known as AG-221 and CC-90007, is a potent and selective IDH2 inhibitor with potential anticancer activity (IDH2 = Isocitrate dehydrogenase 2). The mutations of IDH2 present in certain cancer cells result in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). The production of 2HG is believed to contribute to the formation and progression of cancer. The inhibition of mutant IDH2 and its neoactivity is therefore a potential therapeutic treatment for cancer. Enasidenib is an orally available, selective, potent inhibitor of the mutated IDH2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. Enasidenib has received orphan drug and fast track designations from the U.S. FDA. Enasidenib mesylate is in phase II clinical trials for Solid tumours and phase III clinical trials for the treatment of acute myeloid leukaemia.

Originator

Approval Year

2017
411
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 12.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
IDHIFA

Approved Use

IDHIFA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Launch Date

2017
Primary
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
13 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
822 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30386625
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
49500 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30386625
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
137 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
25.5 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30386625
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENASIDENIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Other AEs: Abdominal distension, Diarrhea...
Other AEs:
Abdominal distension (1 patient)
Diarrhea (1 patient)
Fatigue (1 patient)
Hyperbilirubinemia (3 patients)
Rash (1 patient)
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Disc. AE: Leukocytosis...
Other AEs: Nausea, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Leukocytosis (1%)
Other AEs:
Nausea (all grades, 50%)
Diarrhea (all grades, 43%)
Vomiting (all grades, 34%)
Decreased appetite (all grades, 34%)
Tumor lysis syndrome (all grades, 6%)
Differentiation syndrome (all grades, 14%)
Leukocytosis (all grades, 12%)
Dysgeusia (all grades, 12%)
Nausea (grade 3-4, 5%)
Diarrhea (grade 3-4, 8%)
Vomiting (grade 3-4, 2%)
Decreased appetite (grade 3-4, 4%)
Tumor lysis syndrome (grade 3-4, 6%)
Differentiation syndrome (grade 3-4, 7%)
Leukocytosis (grade 3-4, 6%)
Bilirubin total increased (all grades, 81%)
Calcium decreased (all grades, 74%)
Potassium decreased (all grades, 41%)
Blood phosphorus decreased (all grades, 27%)
Differentiation syndrome (4%)
Leukocytosis (3%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Other AEs: Bilirubin total increased, Calcium decreased...
Other AEs:
Bilirubin total increased (grade 3-4, 15%)
Calcium decreased (grade 3-4, 8%)
Potassium decreased (grade 3-4, 15%)
Blood phosphorus decreased (grade 3-4, 8%)
Hyperbilirubinemia (3.7%)
Hyperbilirubinemia (1.4%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 4.2%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 11.7%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
AEs

AEs

AESignificanceDosePopulation
Abdominal distension 1 patient
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Diarrhea 1 patient
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Fatigue 1 patient
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Rash 1 patient
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Hyperbilirubinemia 3 patients
650 mg 1 times / day multiple, oral
Highest studied dose
Dose: 650 mg, 1 times / day
Route: oral
Route: multiple
Dose: 650 mg, 1 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572791/
Leukocytosis 1%
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Leukocytosis 3%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Differentiation syndrome 4%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Dysgeusia all grades, 12%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Leukocytosis all grades, 12%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Differentiation syndrome all grades, 14%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Blood phosphorus decreased all grades, 27%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Decreased appetite all grades, 34%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Vomiting all grades, 34%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Potassium decreased all grades, 41%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Diarrhea all grades, 43%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Nausea all grades, 50%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Tumor lysis syndrome all grades, 6%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Calcium decreased all grades, 74%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Bilirubin total increased all grades, 81%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Vomiting grade 3-4, 2%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Decreased appetite grade 3-4, 4%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Nausea grade 3-4, 5%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Leukocytosis grade 3-4, 6%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Tumor lysis syndrome grade 3-4, 6%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Differentiation syndrome grade 3-4, 7%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Diarrhea grade 3-4, 8%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Hyperbilirubinemia 1.4%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Hyperbilirubinemia 3.7%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Bilirubin total increased grade 3-4, 15%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Potassium decreased grade 3-4, 15%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Blood phosphorus decreased grade 3-4, 8%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Calcium decreased grade 3-4, 8%
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf
Death grade 5, 4.2%
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
Death grade 5, 11.7%
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000MultidisciplineR.pdf#page=22
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252

inducer
1087
substrate
1193

inhibitor
2438
inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
2153

CYP2B6
926

CYP2C8
1057

CYP2C19
2057

UGT1A1
246

P-gp
1741

BCRP
910

OAT1
725

OATP1B1
1079

OATP1B3
961

OCT2
779

MRP2
499

OAT3
747
P-gp
2052

BCRP
697

MRP2
252

OAT1
395

OAT3
391

OATP1B1
503

OATP1B3
435

OCT2
434

CYP1A2
1197

CYP2B6
776

CYP2C8
810

UGT1A1
479

UGT1A3
470

UGT1A4
399

UGT1A9
423

CYP2C19
1119
CYP2B6
669
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
MRP2
625
 no
MRP2
625
 no
AGI-16903
2
OAT3
749
 no
OATP1B3
970
 no
AGI-16903
2
P-gp
1932
 no
AGI-16903
2
BCRP
985
 yes
BCRP
985
 yes
AGI-16903
2
CYP1A2
2333
 yes
CYP1A2
2333
 yes
AGI-16903
2
CYP2B6
1160
 yes
AGI-16903
2
CYP2B6
1160
 yes
CYP2C19
2141
 yes
CYP2C8
1117
 yes
CYP2C9
2497
 yes
CYP2D6
2546
 yes
CYP3A4
2633
 yes
AGI-16903
2
CYP3A4
2633
 yes
OAT1
730
 yes
OAT1
730
 yes
AGI-16903
2
OAT3
749
 yes
AGI-16903
2
OATP1B1
1095
 yes
OATP1B1
1095
 yes
AGI-16903
2
OATP1B3
970
 yes
OCT2
782
 yes
OCT2
782
 yes
AGI-16903
2
P-gp
1932
 yes
UGT1A1
303
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 no
MRP2
252
 no
OAT1
395
 no
OAT3
391
 no
OATP1B1
503
 no
OATP1B3
435
 no
OCT2
434
 no
P-gp
2052
 no
BCRP
697
 yes
AGI-16903
2
CYP1A2
1197
 yes
CYP1A2
1197
 yes
AGI-16903
2
CYP2B6
776
 yes
CYP2C19
1119
 yes
AGI-16903
2
CYP2C8
810
 yes
CYP2C9
1193
 yes
CYP3A4
1946
 yes
CYP3A4
1946
 yes
AGI-16903
2
P-gp
2052
 yes
AGI-16903
2
UGT1A1
479
 yes
UGT1A3
470
 yes
UGT1A3
470
 yes
AGI-16903
2
UGT1A4
399
 yes
UGT1A9
423
 yes
UGT1A9
423
 yes
AGI-16903
2
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:145374
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:145374
ChemicalBook
CB53044318
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB53044318
MolPort
MolPort-042-676-239
https://www.molport.com/shop/molecule-link/MolPort-042-676-239
ZINC
ZINC000222731806
http://zinc15.docking.org/substances/ZINC000222731806
PubMed

PubMed

TitleDatePubMed
The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors.
2016
IDH2 inhibition in AML: Finally progress?
2015-11-23
[Progress in molecularly targeted therapies for acute myeloid leukemia].
2015-02
Patents

Patents

US2013190287
2
US2016089374
2

Sample Use Guides

In Vivo Use Guide
Continuous 28-day cycles of Enasidenib (AG 221) 100 mg orally (PO) once a day (QD) for 28 days, plus BSC.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Enasidenib has been demonstrated to reduce 2-HG levels by >90% and reverse histone and deoxyribonucleic acid (DNA) hypermethylation in vitro, and to induce differentiation in leukemia cell models
Unknown
Substance Class Chemical
Created
by admin
on Tue Apr 01 16:26:20 GMT 2025
Edited
by admin
on Tue Apr 01 16:26:20 GMT 2025
Record UNII
3T1SS4E7AG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENASIDENIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
enasidenib [INN]
Preferred Name English
ENASIDENIB [MI]
Common Name English
AG-221
Code English
2-METHYL-1-(4-(6-(TRIFLUOROMETHYL)PYRIDIN-2-YL)-6-(2-(TRIFLUOROMETHYL)PYRIDIN-4-YLAMINO)-1,3,5-TRIAZIN-2-YLAMINO)PROPAN-2-OL
Systematic Name English
ENASIDENIB [USAN]
Common Name English
Enasidenib [WHO-DD]
Common Name English
2-PROPANOL, 2-METHYL-1-((4-(6-(TRIFLUOROMETHYL)-2-PYRIDINYL)-6-((2-(TRIFLUOROMETHYL)-4-PYRIDINYL)AMINO)-1,3,5-TRIAZIN-2-YL)AMINO)-
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 434514
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
NDF-RT N0000193615
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
NCI_THESAURUS C137826
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
WHO-ATC L01XX59
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
Code System Code Type Description
CAS
1446502-11-9
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
PUBCHEM
89683805
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
DRUG BANK
DB13874
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
NCI_THESAURUS
C111573
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
CHEBI
145374
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
USAN
DE-54
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
SMS_ID
100000175231
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
FDA UNII
3T1SS4E7AG
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
MERCK INDEX
m12047
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
CAS
1802003-09-3
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
NO STRUCTURE GIVEN
LACTMED
Enasidenib
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
INN
10162
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
WIKIPEDIA
Enasidenib
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
EPA CompTox
DTXSID801027942
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
RXCUI
1940332
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
DRUG CENTRAL
5251
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
DAILYMED
3T1SS4E7AG
Created by admin on Tue Apr 01 16:26:20 GMT 2025 , Edited by admin on Tue Apr 01 16:26:20 GMT 2025
PRIMARY
Related Record Type Details
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
Structure of ENASIDENIB
EXCRETED UNCHANGED
URINE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B15
METABOLIC ENZYME -> SUBSTRATE
Structure of ENASIDENIB MESYLATE
SALT/SOLVATE -> PARENT
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> SUBSTRATE
Structure of ENASIDENIB
CUMULATIVE EXCRETION
FECAL
Structure of ENASIDENIB
EXCRETED UNCHANGED
FECAL
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A4
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B7
METABOLIC ENZYME -> SUBSTRATE
Structure of ENASIDENIB
CUMULATIVE EXCRETION
URINE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2B6
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C8
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C9
METABOLIC ENZYME -> SUBSTRATE
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> NON-SUBSTRATE
CYTOCHROME P450 2D6
METABOLIC ENZYME -> SUBSTRATE
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A3
METABOLIC ENZYME -> SUBSTRATE
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> NON-SUBSTRATE
Related Record Type Details
Structure of AGI-17011
METABOLITE ACTIVE -> PARENT
Structure of AGI-16903
METABOLITE ACTIVE -> PARENT
Related Record Type Details
Structure of ENASIDENIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
PERMEABILITY CHEMICAL MEMBRANE TYPE

Tmax PHARMACOKINETIC
NIH
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