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], [2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

339.4

Topological Polar Surface Area (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 [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 21 hours [5]
Metabolism: The drug is not metabolised [6]
Vd: The volume of distribution (Vd) of drug is 417 L [4]

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	[7], [8], [9]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[10]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

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]	[37]
-----------

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
--------------------


⏷ Show the Full List of 13 Pharmaceutical Excipients of This Drug

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	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
7	Clinical pipeline report, company report or official report of Takeda (2009).
8	Combining a dipeptidyl peptidase-4 inhibitor, alogliptin, with pioglitazone improves glycaemic control, lipid profiles and beta-cell function in db... Br J Pharmacol. 2009 Jun;157(3):415-26.
9	Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
10	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.
11	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
12	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
13	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
14	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
15	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
16	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
17	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
18	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
19	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
20	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
21	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
22	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
23	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
24	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
25	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
26	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
27	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
28	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
29	Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
30	Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
31	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
32	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. (Target id: 1612).
33	Diabetes Treatment. Diabetes Care. 2009 March; 32(3): e25-e30.
34	Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for type 2 diabetes. Cardiol Rev. 2010 Jul-Aug;18(4):213-7.
35	Clinical pipeline report, company report or official report of ShangHai APIs Chemical.
36	Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. Diabetes Obes Metab. 2010 Apr;12(4):348-55.
37	Cerner Multum, Inc. "Australian Product Information.".