Details of the Drug

General Information of Drug (ID: DMS0ZBI)

• Drug Name: AG-221
• Synonyms: AG-221 (IDH2 inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Phase 3	[1]
Acute myeloid leukaemia	2A60	Phase 1/2	[2]

• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 473.4
  Logarithm of the Partition Coefficient (xlogp); 3.5
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 14
• Chemical Identifiers:
  Formula: C19H17F6N7O
  IUPAC Name: 2-methyl-1-[[4-[6-(trifluoromethyl)pyridin-2-yl]-6-[[2-(trifluoromethyl)pyridin-4-yl]amino]-1,3,5-triazin-2-yl]amino]propan-2-ol
  Canonical SMILES: CC(C)(CNC1=NC(=NC(=N1)C2=NC(=CC=C2)C(F)(F)F)NC3=CC(=NC=C3)C(F)(F)F)O
  InChI: 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)
  InChIKey: DYLUUSLLRIQKOE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 89683805
  ChEBI ID: CHEBI:145374
  CAS Number: 1446502-11-9
  TTD ID: D0K7FT
  ACDINA ID: D00230
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Isocitrate dehydrogenase (IDH)	TTDTWV0	IDHC_HUMAN ; IDHP_HUMAN ; IDH3A_HUMAN ; IDH3B_HUMAN ; IDH3G_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Acute myelogenous leukaemia
• ICD Disease Classification: 2A41

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Isocitrate dehydrogenase (IDH)	DTT	IDH1; IDH2; IDH3A; IDH3B; IDH3G	6.06E-02	0.11	0.24

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from AG-221 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Berotralstat	DMWA2DZ	Major	Decreased clearance of Ag-221 due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[4]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Ag-221 due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[5]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Hypromellose acetate succinate	E00696	Not Available	Coating agent; Solubilizing agent; Modified-release agent;Film/membrane-forming agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Enasidenib 100 mg tablet	100 mg	Oral Tablet	Oral
Enasidenib 50 mg tablet	50 mg	Oral Tablet	Oral
Enasidenib Mesylate 100 mg tablet	100 mg	Tablet	Oral
Enasidenib Mesylate 50 mg tablet	50 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] ClinicalTrials.gov (NCT02273739) Study of Orally Administered AG-221 in Subjects With Advanced Solid Tumors, Including Glioma, and With Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation. U.S.National Institutes of Health.
• [3] New Developments in the Pathogenesis and Therapeutic Targeting of the IDH1 Mutation in Glioma. Int J Med Sci. 2015; 12(3): 201-213.
• [4] Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90. [PMID: 6882885]
• [5] Cerner Multum, Inc. "Australian Product Information.".