Details of the Drug

General Information of Drug (ID: DM8WI3R)

• Drug Name: Alogliptin
• Synonyms: 850649-61-5; UNII-JHC049LO86; alogliptina; 2-({6-[(3r)-3-Aminopiperidin-1-Yl]-3-Methyl-2,4-Dioxo-3,4-Dihydropyrimidin-1(2h)-Yl}methyl)benzonitrile; SYR-322; JHC049LO86; (R)-2-((6-(3-aminopiperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile; CHEBI:72323; AK322010; 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}methyl)benzonitrile; vipidia; Alogliptin [INN]; Alogliptin (SYR-322); alogliptinum; alogliptine; HSDB 8203; UNII-JHC049LO86

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 339.4
  Logarithm of the Partition Coefficient (xlogp); 0.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Clearance: The renal clearance of drug is 9.6 L/h []
  Half-life: The concentration or amount of drug in body reduced by one-half in 21 hours [2]
  Metabolism: The drug is not metabolised []
  Vd: The volume of distribution (Vd) of drug is 417 L []

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Hypoglycaemia	Not Available	CYP3A4	OTQGYY83	[3]
Hypoglycaemia	Not Available	CYP2D6	OTZJC802	[3]

• Chemical Identifiers:
  Formula: C18H21N5O2
  IUPAC Name: 2-[[6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxopyrimidin-1-yl]methyl]benzonitrile
  Canonical SMILES: CN1C(=O)C=C(N(C1=O)CC2=CC=CC=C2C#N)N3CCC[C@H](C3)N
  InChI: InChI=1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1
  InChIKey: ZSBOMTDTBDDKMP-OAHLLOKOSA-N
• Cross-matching ID:
  PubChem CID: 11450633
  ChEBI ID: CHEBI:72323
  CAS Number: 850649-61-5
  DrugBank ID: DB06203
  TTD ID: D0NJ5H
  INTEDE ID: DR0071
  ACDINA ID: D00022

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Drug Response	[3]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Drug Response	[3]
Dipeptidyl peptidase 4 (DPP4)	OT16MVL9	DPP4_HUMAN	Protein Interaction/Cellular Processes	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Type-2 diabetes
• ICD Disease Classification: 5A11

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dipeptidyl peptidase 4 (DPP-4)	DTT	DPP4	9.54E-01	-0.27	-1.85
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.04E-01	-2.88E-01	-5.42E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alogliptin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Alogliptin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[7]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Alogliptin 12.5 mg tablet	12.5 mg	Oral Tablet	Oral
Alogliptin 25 mg tablet	25 mg	Oral Tablet	Oral
Alogliptin 6.25 mg tablet	6.25 mg	Oral Tablet	Oral
Alogliptin Benzoate eq 6.25mg base tablet	eq 6.25mg base	Tablet	Oral
Alogliptin Benzoate eq 12.5mg base tablet	eq 12.5mg base	Tablet	Oral
Alogliptin Benzoate eq 25mg base tablet	eq 25mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6319).
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [4] Clinical pipeline report, company report or official report of Takeda (2009).
• [5] An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus. Clin Exp Pharmacol Physiol. 2015 Dec;42(12):1225-38.
• [6] Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual screening and validation through molecular dynamics simulations. J Mol Model. 2014 Apr;20(4):2118. doi: 10.1007/s00894-014-2118-7. Epub 2014 Apr 1.
• [7] Cerner Multum, Inc. "Australian Product Information.".