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Details

Stereochemistry ACHIRAL
Molecular Formula C19H17F6N7O
Molecular Weight 473.3757
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENASIDENIB

SMILES

CC(C)(CN=c1nc(-c2cccc(C(F)(F)F)n2)[nH]c(=Nc3ccnc(c3)C(F)(F)F)[nH]1)O

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

Description
Curator's Comment:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
12 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1501459200000
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
822 ng/mL
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
13 μg/mL
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
49500 ng × h/mL
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
25.5 h
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
137 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Abdominal distension, Diarrhea...
Other AEs:
Abdominal distension (1 patient)
Diarrhea (1 patient)
Fatigue (1 patient)
Hyperbilirubinemia (3 patients)
Rash (1 patient)
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
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:
unhealthy, adult
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 11.7%)
Sources:
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:
unhealthy, adult
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 4.2%)
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
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:
unhealthy, adult
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
PubMed

PubMed

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

Sample Use Guides

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
Name Type Language
ENASIDENIB
INN   USAN   WHO-DD  
USAN   INN  
Official 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
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
ENASIDENIB [WHO-DD]
Common Name English
AG 221 [WHO-DD]
Common Name English
ENASIDENIB [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 434514
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
NDF-RT N0000193615
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
NCI_THESAURUS C137826
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
WHO-ATC L01XX59
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
Code System Code Type Description
CAS
1446502-11-9
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
PUBCHEM
89683805
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
DRUG BANK
DB13874
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
NCI_THESAURUS
C111573
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
FDA UNII
3T1SS4E7AG
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
MERCK INDEX
M12047
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
CAS
1802003-09-3
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
NO STRUCTURE GIVEN
LACTMED
Enasidenib
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
INN
10162
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
RXCUI
1940332
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY
DRUG CENTRAL
5251
Created by admin on Sat Jun 26 13:48:45 UTC 2021 , Edited by admin on Sat Jun 26 13:48:45 UTC 2021
PRIMARY