ALOGLIPTIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H21N5O2
Molecular Weight	339.3916
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC3=C(C=CC=C3)C#N)C1=O

InChI

InChIKey=ZSBOMTDTBDDKMP-OAHLLOKOSA-N

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

HIDE SMILES / InChI

Molecular Formula	C18H21N5O2
Molecular Weight	339.3916
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022271s009lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.takeda.com/news/2013/20130924_5997.html; http://www.ncbi.nlm.nih.gov/pubmed/22651127; http://www.ncbi.nlm.nih.gov/pubmed/17441705

Alogliptin (trade name Nesina in the US and Vipidia in Europe) is an orally administered anti-diabetic drug in the DPP-4 inhibitor class, discovered by Takeda Pharmaceutical Company's wholly owned subsidiary, Takeda San Diego, Inc. (former Syrrx) which was acquired by Takeda in 2005. Alogliptin does not decrease the risk of heart attack and stroke. Like other members of the gliptin class, it causes little or no weight gain, exhibits relatively little risk of causing hypoglycemia, and exhibits relatively modest glucose-lowering activity. Alogliptin and other gliptins are commonly used in combination with metformin in patients whose diabetes cannot adequately be controlled with metformin alone.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dipeptidyl peptidase 4 8 Target ID: P27487 Gene ID: 1803.0 Gene Symbol: DPP4 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022271s009lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022271s009lbl.pdf	Secondary		Approved 8429	NESINA Approved Use Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitation of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis. Launch Date 1.35907194E12

C_max

Value	Dose	Analyte	Population
165 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25936384/	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	[NO STEREO] ALOGLIPTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
154.83 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
335.36 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
75.38 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg 1 times / day multiple, oral dose: 12.5 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
114.08 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg single, oral dose: 25 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
246 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg single, oral dose: 50 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
55.28 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg single, oral dose: 12.5 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:

AUC

Value	Dose	Analyte	Population
1511 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25936384/	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	[NO STEREO] ALOGLIPTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1174.76 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg single, oral dose: 25 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
1625.58 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg 1 times / day multiple, oral dose: 25 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
2488.48 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg single, oral dose: 50 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
3389.21 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
601.65 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg single, oral dose: 12.5 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
842.17 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg 1 times / day multiple, oral dose: 12.5 mg route of administration: oral experiment type: multiple co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
1674.87999999999 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg single, oral dose: 25 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
3306.68 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg single, oral dose: 50 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
895.28 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg single, oral dose: 12.5 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:

T_1/2

Value	Dose	Analyte	Population
16.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25936384/	25 mg 1 times / day steady-state, oral dose: 25 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	[NO STEREO] ALOGLIPTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022271s011lbl.pdf	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	[NO STEREO] ALOGLIPTIN plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
20.67 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	12.5 mg single, oral dose: 12.5 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
19.45 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	25 mg single, oral dose: 25 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:
17 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01391663	50 mg single, oral dose: 50 mg route of administration: oral experiment type: single co-administered:	ALOGLIPTIN plasma	Homo sapiens population: healthy age: Adults sex: food status:

F_unbound

Value	Dose	Co-administered	Analyte	Population
80% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022271s011lbl.pdf	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		[NO STEREO] ALOGLIPTIN plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18405789	healthy, 26.6 years (range: 18-55 years) n = 5 Health Status: healthy Age Group: 26.6 years (range: 18-55 years) Sex: M Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/18405789	Sources: https://pubmed.ncbi.nlm.nih.gov/18405789
400 mg 1 times / day steady, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18405788/	unhealthy, 55.6 years (range: 18 - 75 years) n = 16 Health Status: unhealthy Condition: type 2 diabetes Age Group: 55.6 years (range: 18 - 75 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/18405788/	Other AEs: Headache, Dizziness... Other AEs: Headache (6 patients) Dizziness (4 patients) Constipation (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/18405788/
25 mg 1 times / day steady, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: steady Dose: 25 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000MedRedt2.pdf Page: p. 48	unhealthy, adult n = 6626 Health Status: unhealthy Age Group: adult Population Size: 6626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000MedRedt2.pdf Page: p. 48	Disc. AE: Acute myocardial infarction, Angina unstable... AEs leading to discontinuation/dose reduction: Acute myocardial infarction (8 patients) Angina unstable (2 patients) Myocardial infarction (12 patients) Abdominal pain (2 patients) Diarrhea (1 patient) Nausea (3 patients) Edema peripheral (4 patients) Blood creatinine increased (6 patients) Creatinine renal clearance abnormal (3 patients) Creatinine renal clearance decreased (22 patients) Lipase increased (10 patients) Hyperglycemia (3 patients) Dizziness (4 patients) Headache (2 patients) Renal impairment (13 patients) Rash (2 patients) Rash pruritic (3 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000MedRedt2.pdf Page: p. 48

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 inducer 389	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278 OAT1 599 OAT3 642 OCT2 647	P-gp 1537 OAT1 326 OAT3 339 OCT2 355	CYP1A2 701 CYP2B6 547 CYP2C19 293 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166.0	little or no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166.0	little or no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166.0	little or no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166.0	little or no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	no [IC50 78 uM]	no (co-administration study) Comment: mechanism-based inhibition using midazolam; did not change in vivo 3A4 substrates (midazolam and atorvastatin exposure) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	no
OAT1 603	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
OAT3 644	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
OCT2 648	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0	some [IC50 >100 uM]	weak (co-administration study) Comment: increased dextromethorphan AUC by 26% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=165 Page: 165.0
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166;62	yes	no (co-administration study) Comment: induction at 100 µM was 27.6% as effective as rifampin; did not affect exposure of 3A4 substrates (midazolam and atorvastatin) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166;62

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166151.0	inconclusive	no (co-administration study) Comment: cyclosporin does not have significant impact on plasma PK of SYR-322 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=166 Page: 166151.0
OAT1 326	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
OAT3 339	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
OCT2 355	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136081/	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000ClinPharmR.pdf#page=164 Page: 164.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022271Orig1s000PharmR.pdf#page=109 Page: 109.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:72323	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72323
ChemicalBook	CB91011068	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB91011068
MolPort	MolPort-005-933-065	https://www.molport.com/shop/molecule-link/MolPort-005-933-065
Selleck Chemicals	alogliptin-syr-322	http://www.selleckchem.com/products/alogliptin-syr-322.html
ZINC	ZINC000014961096	http://zinc15.docking.org/substances/ZINC000014961096
eMolecules	31229135	https://www.emolecules.com/cgi-bin/more?vid=31229135

PubMed

Title	Date	PubMed
Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV.	2007 May 17	17441705
Alogliptin, a potent and selective dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes.	2008 Apr	18393107
Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis.	2008 Oct 27	18954434
Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia.	2009 Dec	19758359
Alogliptin: a new, highly selective dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.	2009 Feb	19191685
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy.	2009 Feb	19125778
Incretin-based therapies: new treatments for type 2 diabetes in the new millennium.	2009 Jun	19707284
DPP4 inhibitors: from sitagliptin monotherapy to the new alogliptin-pioglitazone combination therapy.	2009 Mar	19259628
Diabetes treatment.	2009 Mar	19246581
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.	2009 Oct	19650752
Coadministration of pioglitazone or glyburide and alogliptin: pharmacokinetic drug interaction assessment in healthy participants.	2009 Oct	19622714
Dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: safety, tolerability, and efficacy.	2010	21701614
DPP-4 (CD26) inhibitor alogliptin inhibits TLR4-mediated ERK activation and ERK-dependent MMP-1 expression by U937 histiocytes.	2010 Dec	20843518
Incretin concepts.	2010 Feb	20103551
Type 2 diabetes mellitus and the cardiometabolic syndrome: impact of incretin-based therapies.	2010 Jul 9	21437091
Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin.	2010 Mar 29	21437074
New treatments in the management of type 2 diabetes: a critical appraisal of saxagliptin.	2010 May 10	21437082
Initial combination therapy with alogliptin and pioglitazone in drug-naïve patients with type 2 diabetes.	2010 Nov	20724648
Exenatide once weekly: clinical outcomes and patient satisfaction.	2010 Sep 7	20859458

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose in patients with normal renal function or mild renal impairment is 25 mg once daily. Can be taken with or without food. Adjust dose if moderate or severe renal impairment or end-stage renal disease (ESRD).

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:57:30 UTC 2023` Edited by `admin` on `Sat Dec 16 17:57:30 UTC 2023`
Record UNII	JHC049LO86
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALOGLIPTIN

Official Name

English

ALOGLIPTIN [MI]

Common Name

English

Alogliptin [WHO-DD]

Common Name

English

ALOGLIPTIN [VANDF]

Common Name

English

alogliptin [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

A10BH04