Details
Stereochemistry | MIXED |
Molecular Formula | C18H25N3O2.ClH |
Molecular Weight | 351.871 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
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=TUAZNHHHYVBVBR-NHKADLRUSA-N
InChI=1S/C18H25N3O2.ClH/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/t10?,11?,12-,13+,14+,15-,17?,18?;/m1./s1
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 |
DescriptionSources: http://www.drugbank.ca/drugs/DB06335Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/monograph/saxagliptin-hydrochloride.html
Sources: http://www.drugbank.ca/drugs/DB06335
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
Sources: http://adisinsight.springer.com/drugs/800016588
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL284 |
30.3 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Onglyza Approved UseDiabetes 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 Date2009 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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%) Sources: Page: 4Rash (0.2%) Blood creatinine increased (0.3%) Blood creatine phosphokinase increased (0.1%) |
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%) Sources: Page: 4Rash (0.3%) Blood creatine phosphokinase increased (0.2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | |||
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 unchagned Page: 17.0 |
||
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 |
||
Page: 16.0 |
no | no (co-administration study) Comment: administration with metformin did not alter PK of metformin Page: 16.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | no (co-administration study) Comment: administered with digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
no | no (co-administration study) Comment: administered with digoxin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_ClinPharmR_P1.pdf#page=39 Page: 39.0 |
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022350s000_PharmR_P5.pdf#page=31 Page: 31.0 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19904014
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
Edited
Fri Dec 15 17:17:13 GMT 2023
by
admin
on
Fri Dec 15 17:17:13 GMT 2023
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Record UNII |
Z8J84YIX6L
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C98086
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C81702
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100000115533
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