Saxagliptin Anhydrous

Summary

Saxagliptin Anhydrous (CHEMBL385517) is an approved small-molecule hypoglycemic agent targeting DPP4.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 1 (DPP4)
• Clinical trials: 106
• Chemistry: 315.4 Da · C18H25N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL385517
Name	Saxagliptin Anhydrous
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11243969
ChEBI	CHEBI:71272
Molecular formula	C18H25N3O2
Molecular weight	315.4
InChIKey	QGJUIPDUBHWZPV-SGTAVMJGSA-N

SMILES: C1[C@@H]2C[C@@H]2N([C@@H]1C#N)C(=O)[C@H](C34CC5CC(C3)CC(C5)(C4)O)N

IUPAC name: (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile

ChEBI definition: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2S)-amino(3-hydroxyadamantan-1-yl)acetic acid with the amino group of (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carbonitrile. Used in its monohydrate form for the treatment of Type II diabetes.

Pharmacological roles (ChEBI): hypoglycemic agent, EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor.

Also known as: BMS-477118, Saxagliptin anhydrous, SBMS-477118, saxagliptin, Saxagliptin, SID144206461, SAXAGLIPTIN (BMS-477118,ONGLYZA), Saxagliptin (BMS-477118;Onglyza), SAXAGLIPTIN

Parent form; salt/anhydrous children: CHEMBL1201743, CHEMBL2103745, CHEMBL3542376

Patent coverage: 4,605 distinct patent families (18,553 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DPP4	dipeptidyl peptidase 4	Inhibition	9.2	0%	P27487

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Dipeptidyl peptidase 4, Cytochrome P450 3A4, Dipeptidyl peptidase 4, Dipeptidyl peptidase 8, Dipeptidyl peptidase 9.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DPP4	9.52	Kd	0.3	nM	CHEMBL_ACT_19442630
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_1487117
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_1774983
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_1997822
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_2605865
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_2713694
DPP4	9.22	Ki	0.6	nM	CHEMBL_ACT_29106215
DPP4	9.22	IC50	0.6	nM	CHEMBL_ACT_6311244
DPP4	8.89	Ki	1.3	nM	CHEMBL_ACT_25636174
DPP4	8.82	IC50	1.5	nM	CHEMBL_ACT_24967494
DPP4	8.82	IC50	1.5	nM	CHEMBL_ACT_25636151
P28843	8.72	IC50	1.9	nM	CHEMBL_ACT_25636169
DPP4	8.52	IC50	3	nM	CHEMBL_ACT_2697712
DPP4	8.47	IC50	3.37	nM	CHEMBL_ACT_12044047
DPP4	8.47	IC50	3.4	nM	CHEMBL_ACT_3313853
DPP4	7.8	Kd	15.9	nM	CHEMBL_ACT_19442666
DPP4	7.52	IC50	30.3	nM	CHEMBL_ACT_13910924
DPP4	7.3	IC50	50	nM	CHEMBL_ACT_13317270
DPP4	7.3	IC50	50	nM	CHEMBL_ACT_14583364
DPP4	7.3	IC50	50	nM	CHEMBL_ACT_25636163
DPP9	7.15	Ki	71	nM	CHEMBL_ACT_1774985
DPP9	7.01	Ki	98	nM	CHEMBL_ACT_25636122
DPP9	7	IC50	100	nM	CHEMBL_ACT_3313797
DPP9	6.98	IC50	104	nM	CHEMBL_ACT_12044035
DPP8	6.89	Ki	130	nM	CHEMBL_ACT_1774984
DPP8	6.62	IC50	240	nM	CHEMBL_ACT_3313825
DPP8	6.61	IC50	244	nM	CHEMBL_ACT_12044029
DPP8	6.29	Ki	508	nM	CHEMBL_ACT_25636119

Target pathways

Aggregated over 1 target gene(s): DPP4.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	DPP4
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	DPP4

Dominant GO biological processes

GO term	Targets
behavioral fear response	1
response to hypoxia	1
proteolysis	1
cell adhesion	1
positive regulation of cell population proliferation	1
negative regulation of extracellular matrix disassembly	1
peptide hormone processing	1
receptor-mediated endocytosis of virus by host cell	1
T cell costimulation	1
regulation of cell-cell adhesion mediated by integrin	1
locomotory exploration behavior	1
psychomotor behavior	1
T cell activation	1
endothelial cell migration	1
symbiont entry into host cell	1

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 106.

Phase distribution

Phase	Trials
PHASE4	35
PHASE3	35
PHASE1	18
Not specified	10
PHASE2	6
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01006590	PHASE4	COMPLETED	Efficacy and Tolerability of Saxagliptin add-on Compared to Uptitration of Metformin in Patients With Type 2 Diabetes
NCT01006603	PHASE4	COMPLETED	Saxagliptin Compared to Glimepiride in Elderly Type 2 Diabetes Patients, With Inadequate Glycemic Control on Metformin
NCT01107886	PHASE4	COMPLETED	Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications
NCT01206647	PHASE4	UNKNOWN	Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus
NCT01267448	PHASE4	COMPLETED	Outpatient Discharge Therapy With Saxagliptin+MetforminXR vs GlipizideXL for Type 2 Diabetes With Severe Hyperglycemia
NCT01527747	PHASE4	SUSPENDED	Effects of DPP-4 Inhibition on Triglycerides
NCT01548651	PHASE4	TERMINATED	Effect of Saxagliptin Treatment on Myocardial Fat Content, and Monocyte Inflammation
NCT01552018	PHASE4	COMPLETED	Saxagliptin and Atherosclerosis
NCT01608724	PHASE4	COMPLETED	The Efficacy and Safety Study in Patients With Type 2 Diabetes Mellitus
NCT01660386	PHASE4	UNKNOWN	Study of Comparing the Different Effect of DPP-4 Inhibitors and Sulfonylurea by Using Biphase-Hyperglycemic Clamp
NCT01765270	PHASE4	TERMINATED	Mechanistic Assessment of the Properties of Saxagliptin in Subjects Undergoing Coronary Artery Bypass Graft Surgery
NCT01768208	PHASE4	UNKNOWN	Metabolomic Variations in the Saxagliptin-Treated Type 2 Diabetes Mellitus Patients
NCT01960205	PHASE4	UNKNOWN	Effect of Saxagliptin on Pre-Diabetes Mellitus and Obesity
NCT02024477	PHASE4	COMPLETED	Effect of Saxagliptin on EPCs as a Cellular Biomarker for Evaluating Endothelial Dysfunction in Early T2DM Patients
NCT02089438	PHASE4	COMPLETED	DPP-4 Inhibition, Incretins and Islet Function
NCT02104739	PHASE4	COMPLETED	Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
NCT02182895	PHASE4	COMPLETED	Safety and Efficacy of Saxagliptin for Glycemic Control in Non-Critically Ill Hospitalized Patient
NCT02243176	PHASE4	COMPLETED	24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy, Safety and Tolerability of Saxagliptin Compared With Acarbose When in Combination With Metformin in Patients With T2D Inadequately Controlled With Metformin Monotherapy
NCT02280486	PHASE4	COMPLETED	Efficacy and Safety of Saxagliptin VS. Glimepiride in Chinese T2DM Patients Controlled Inadequately With Metformin
NCT02285985	PHASE4	COMPLETED	Effects of Saxagliptin on Adipose Tissue Inflammation in Humans
NCT02304081	PHASE4	COMPLETED	Saxagliptin in Combination With Dapagliflozin - Effects on Islet Cell Function
NCT02307695	PHASE4	UNKNOWN	The Effect of Saxagliptin on Glucose Fluctuation and Immune Regulation in Patients With Type 1 Diabetes
NCT02386943	PHASE4	UNKNOWN	Study on Exploring the Effect of DPP-4 Inhibitors on β-cell Function by Using the Two-step Hyperglycemic Clamp
NCT02407899	PHASE4	COMPLETED	Protective Effects of Saxagliptin (And Vitamin D3) on β Cell Function in Adult-onset Latent Autoimmune Diabetes
NCT02462369	PHASE4	UNKNOWN	Saxagliptin’s Effects on Microalbuminuria Improvement in Type 2 Diabetic Patients
NCT02471404	PHASE4	COMPLETED	Efficacy and Safety of Dapagliflozin and Dapagliflozin Plus Saxagliptin in Combination With Metformin in Type 2 Diabetes Patients Compared With Sulphonylurea
NCT02481479	PHASE4	COMPLETED	Saxagliptin and Cardiac Structure and Function
NCT02605772	PHASE4	UNKNOWN	Safety and Efficacy of Acarbose+Saxagliptin Compared With Metformin+Saxagliptin in Patients With Type 2 Diabetes
NCT02742233	PHASE4	UNKNOWN	Dipeptidyl Peptidase 4 Inhibition Facilitate Healing of Diabetic Ulcers
NCT02765204	PHASE4	COMPLETED	A Single-dose Cross-over Study to Assess Direct and Indirect Effects of Dapagliflozin on Pancreatic Alpha and Beta Cells in Patients With Type 2 Diabetes
NCT02917031	PHASE4	COMPLETED	Mechanistic Evaluation of Glucose-lowering Strategies in Patients With Heart Failure
NCT02920801	PHASE4	COMPLETED	Study About Effect of Saxagliptin on Circulating Endothelial Progenitor Cells and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients
NCT03660683	PHASE4	TERMINATED	Effect of Saxagliptin and Dapagliflozin on Endothelial Progenitor Cell in Patients With Type 2 Diabetes Mellitus
NCT04445714	PHASE4	COMPLETED	To Assess Safety of Fixed Dose Combination of Dapagliflozin and Saxagliptin in Type 2 Diabetes Mellitus Patients
NCT04521049	PHASE4	COMPLETED	Tubular Markers in Response to Saxagliptin Therapy
NCT00121641	PHASE3	COMPLETED	Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise
NCT00121667	PHASE3	COMPLETED	Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone
NCT00295633	PHASE3	COMPLETED	A Study Assessing Saxagliptin Treatment in Type 2 Diabetic Subjects Who Are Not Controlled With TZD Therapy Alone
NCT00313313	PHASE3	COMPLETED	A Study of Saxagliptin in Subjects With Type 2 Diabetes Who Have Inadequate Blood Sugar Control With Sulfonylureas
NCT00316082	PHASE3	COMPLETED	Study of BMS-477118 as Monotherapy With Titration in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 4 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

28 molecules share ≥1 primary target. Top 28 by shared-target count:

Molecule	Source	Status	Shared targets
ALOGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	DPP4
LINAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	DPP4
ANAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
EVOGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
GEMIFLOXACIN	ChEMBL	Phase 4 (approved)	DPP4
GOSOGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
METFORMIN	ChEMBL	Phase 4 (approved)	DPP4
OMARIGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
SITAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
TENELIGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
TRELAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
VIDARABINE	ChEMBL	Phase 4 (approved)	DPP4
VILDAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
CAFFEIC ACID	ChEMBL	Phase 3	DPP4
DBPR-108	ChEMBL	Phase 3	DPP4
DUTOGLIPTIN	ChEMBL	Phase 3	DPP4
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	DPP4
QUERCETIN	ChEMBL	Phase 3	DPP4
RESVERATROL	ChEMBL	Phase 3	DPP4
RETAGLIPTIN	ChEMBL	Phase 3	DPP4
TALABOSTAT	ChEMBL	Phase 3	DPP4
CARMEGLIPTIN	ChEMBL	Phase 2	DPP4
COFROGLIPTIN	ChEMBL	Phase 2	DPP4
FLAVONE	ChEMBL	Phase 2	DPP4
GALLIC ACID	ChEMBL	Phase 2	DPP4
GENISTEIN	ChEMBL	Phase 2	DPP4
LUTEOLIN	ChEMBL	Phase 2	DPP4
Carfilzomib	PubChem	Approved	DPP4