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Details

Stereochemistry MIXED
Molecular Formula C18H25N3O2.ClH.2H2O
Molecular Weight 387.901
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAXAGLIPTIN HYDROCHLORIDE DIHYDRATE

SMILES

O.O.Cl.[H][C@@]12C[C@]1([H])N([C@@H](C2)C#N)C(=O)[C@@H](N)C34CC5CC(CC(O)(C5)C3)C4

InChI

InChIKey=AJXATZPZZXZZRE-ZEGDOHPJSA-N
InChI=1S/C18H25N3O2.ClH.2H2O/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17;;;/h10-15,23H,1-7,9,20H2;1H;2*1H2/t10?,11?,12-,13+,14+,15-,17?,18?;;;/m1.../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C18H25N3O2
Molecular Weight 315.41
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 4 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/monograph/saxagliptin-hydrochloride.html

Saxagliptin is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.

Originator

Curator's Comment: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
30.3 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Onglyza

Approved Use

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM) as monotherapy or in combination therapy.

Launch Date

2009
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
24 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
78 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SAXAGLIPTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10 mg 1 times / day steady, oral
Highest studied dose
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources: Page: table 4
unhealthy, adult
n = 98
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: M+F
Population Size: 98
Sources: Page: table 4
Disc. AE: Adverse event...
AEs leading to
discontinuation/dose reduction:
Adverse event (5.1%)
Sources: Page: table 4
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Disc. AE: Lymphopenia, Rash...
AEs leading to
discontinuation/dose reduction:
Lymphopenia (0.1%)
Rash (0.2%)
Blood creatinine increased (0.3%)
Blood creatine phosphokinase increased (0.1%)
Sources: Page: 4
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Disc. AE: Lymphopenia, Rash...
AEs leading to
discontinuation/dose reduction:
Lymphopenia (0.5%)
Rash (0.3%)
Blood creatine phosphokinase increased (0.2%)
Sources: Page: 4
AEs

AEs

AESignificanceDosePopulation
Adverse event 5.1%
Disc. AE
10 mg 1 times / day steady, oral
Highest studied dose
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources: Page: table 4
unhealthy, adult
n = 98
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: M+F
Population Size: 98
Sources: Page: table 4
Blood creatine phosphokinase increased 0.1%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Lymphopenia 0.1%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Rash 0.2%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Blood creatinine increased 0.3%
Disc. AE
2.5 mg 1 times / day steady, oral
Recommended
Dose: 2.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 2.5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Blood creatine phosphokinase increased 0.2%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Rash 0.3%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
Lymphopenia 0.5%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources: Page: 4
unhealthy, adult
n = 882
Health Status: unhealthy
Condition: type 2 diabetes
Age Group: adult
Sex: unknown
Population Size: 882
Sources: Page: 4
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
no
no
no
no
no
no
no
no
no
no
no (co-administration study)
Comment: administration with simvastatin did not alter PK of metformin; administration with diltiazem increased the plasma Cmax of diltiazem by 16%, AUC of diltiazem was unchagned
Page: 17.0
no
no (co-administration study)
Comment: administration with simvastatin did not alter PK of metformin; administration with diltiazem increased the plasma Cmax of diltiazem by 16%, AUC of diltiazem was unchanged; administration with ketoconazole decreased Cmax and AUC of ketoconazole by 16% and 13%, respectively;
Page: 17.0
no
no (co-administration study)
Comment: administration with metformin did not alter PK of metformin
Page: 16.0
no
no (co-administration study)
no
no (co-administration study)
no
unlikely (co-administration study)
Comment: no concentration and time-dependent inhibtion; administration with pioglitazone increased the plasma Cmax of glyburide by 14%, AUC was unchanged.
Page: 39.0
no
unlikely (co-administration study)
Comment: no concentration and time-dependent inhibtion; administration with glyburide increased the plasma Cmax of glyburide by 16%, AUC was unchanged.
Page: 39.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: ketoconazole increased the Cmax for saxagliptin by 62% and the AUC by 2.5-fold
Page: 38,42
minor
minor
minor
no
no
no
no
no
no
no
no
yes
no (co-administration study)
Comment: administration with digoxin did not alter PK of saxagliptin
Page: 39.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

Diabetes Mellitus Monotherapy Oral 2.5 or 5 mg once daily.1 Higher dosages (e.g., 10 mg once daily) did not provide additional benefit in clinical trials and are not recommended by manufacturer.
Route of Administration: Oral
Saxagliptin inhibited rat plasma DPP-IV activity in vitro with an IC(50) value of 2.00 nmol/l
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:34:10 GMT 2023
Edited
by admin
on Sat Dec 16 08:34:10 GMT 2023
Record UNII
4N19ON48ZN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SAXAGLIPTIN HYDROCHLORIDE DIHYDRATE
Common Name English
2-AZABICYCLO(3.1.0)HEXANE-3-CARBONITRILE, 2-((2S)-2-AMINO-2-(3-HYDROXYTRICYCLO(3.3.1.13,7)DEC-1-YL)ACETYL)-, HYDROCHLORIDE, HYDRATE (1:1:2), (1S,3S,5S)-
Systematic Name English
Code System Code Type Description
SMS_ID
300000047033
Created by admin on Sat Dec 16 08:34:11 GMT 2023 , Edited by admin on Sat Dec 16 08:34:11 GMT 2023
PRIMARY
FDA UNII
4N19ON48ZN
Created by admin on Sat Dec 16 08:34:11 GMT 2023 , Edited by admin on Sat Dec 16 08:34:11 GMT 2023
PRIMARY
CAS
1073057-20-1
Created by admin on Sat Dec 16 08:34:11 GMT 2023 , Edited by admin on Sat Dec 16 08:34:11 GMT 2023
PRIMARY
PUBCHEM
91617922
Created by admin on Sat Dec 16 08:34:11 GMT 2023 , Edited by admin on Sat Dec 16 08:34:11 GMT 2023
PRIMARY
EPA CompTox
DTXSID30861540
Created by admin on Sat Dec 16 08:34:11 GMT 2023 , Edited by admin on Sat Dec 16 08:34:11 GMT 2023
PRIMARY
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