Details of the Drug

General Information of Drug (ID: DMGXENV)

Drug Name

Saxagliptin

Synonyms

Onglyza; BMS 477118-11; BMS-477118; Kombiglyze XR (TN); OPC-262; Onglyza (TN); BMS-477118-11; (1S,5S)-2-[2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile; 2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2S)-amino(3-hydroxytricyclo[3.3

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

315.4

Logarithm of the Partition Coefficient (xlogp)

0.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance: The renal clearance of drug is 14 L/h []
Elimination: 24% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [3]
Metabolism: The drug is metabolized via the cytochrome P450 3A4/5 (CYP3A4/5) []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2265 micromolar/kg/day [4]
Unbound Fraction: The unbound fraction of drug in plasma is 1% [3]
Vd: The volume of distribution (Vd) of drug is 151 L []
Water Solubility: The ability of drug to dissolve in water is measured as 17.6 mg/mL [2]

Chemical Identifiers

Formula: C18H25N3O2
IUPAC Name: (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
Canonical SMILES: C1[C@@H]2C[C@@H]2N([C@@H]1C#N)C(=O)[C@H](C34CC5CC(C3)CC(C5)(C4)O)N
InChI: InChI=1S/C18H25N3O2/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/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
InChIKey: QGJUIPDUBHWZPV-SGTAVMJGSA-N

Cross-matching ID

PubChem CID: 11243969
ChEBI ID: CHEBI:71272
CAS Number: 361442-04-8
DrugBank ID: DB06335
TTD ID: D0K9MY
VARIDT ID: DR00226
INTEDE ID: DR1465
ACDINA ID: D00616

Combinatorial Drugs (CBD)

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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	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[6]
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[7]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[6]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[9]
Cytochrome P450 3A5 (CYP3A5)_{Main DME}	DEIBDNY	CP3A5_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Dipeptidyl peptidase 4 (DPP4)	OT16MVL9	DPP4_HUMAN	Gene/Protein Processing	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTP	OATP4C1	9.91E-01	2.18E-01	6.01E-01
Organic anion transporter 3 (SLC22A8)	DTP	OAT3	6.49E-01	3.37E-03	6.66E-02
P-glycoprotein 1 (ABCB1)	DTP	P-GP	2.30E-01	3.06E-01	7.43E-01
Multidrug resistance-associated protein 1 (ABCC1)	DTP	MRP1	3.82E-01	1.16E-01	9.50E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	8.58E-01	-3.73E-03	-1.00E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Saxagliptin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Saxagliptin caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Saxagliptin caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[12]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of Saxagliptin caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[13]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[14]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Saxagliptin caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[11]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Saxagliptin caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[13]
Palbociclib	DMD7L94	Moderate	Decreased metabolism of Saxagliptin caused by Palbociclib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[13]
PF-04449913	DMSB068	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[13]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Saxagliptin caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[13]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Saxagliptin caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[13]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Saxagliptin caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[11]
Boceprevir	DMBSHMF	Moderate	Decreased metabolism of Saxagliptin caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[13]
GS-5885	DMSL3DX	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by GS-5885.	Hepatitis virus infection [1E50-1E51]	[15]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Saxagliptin caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[13]
Etravirine	DMGV8QU	Moderate	Increased metabolism of Saxagliptin caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
BMS-201038	DMQTAGO	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by BMS-201038.	Hyper-lipoproteinaemia [5C80]	[16]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Saxagliptin caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[13]
Suvorexant	DM0E6S3	Moderate	Decreased metabolism of Saxagliptin caused by Suvorexant mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[13]
Crizotinib	DM4F29C	Moderate	Decreased metabolism of Saxagliptin caused by Crizotinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[13]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Saxagliptin caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[11]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Saxagliptin caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[13]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Saxagliptin caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[13]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Saxagliptin caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[13]
Ibrutinib	DMHZCPO	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by Ibrutinib.	Mature B-cell lymphoma [2A85]	[13]
Vemurafenib	DM62UG5	Moderate	Increased metabolism of Saxagliptin caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[11]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Saxagliptin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[12]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[17]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Saxagliptin caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[13]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Saxagliptin due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[18]
Netupitant	DMEKAYI	Moderate	Decreased metabolism of Saxagliptin caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[13]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of Saxagliptin caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[13]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Saxagliptin caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[13]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Saxagliptin caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[19]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Saxagliptin caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[20]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Saxagliptin caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[13]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Saxagliptin caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[11]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Saxagliptin caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[13]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Saxagliptin caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[13]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Saxagliptin caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[13]
Armodafinil	DMGB035	Minor	Increased metabolism of Saxagliptin caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[21]
LEE011	DMMX75K	Moderate	Decreased metabolism of Saxagliptin caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[13]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Saxagliptin caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[22]
Brilinta	DMBR01X	Moderate	Decreased metabolism of Saxagliptin caused by Brilinta mediated inhibition of CYP450 enzyme.	Thrombosis [DB61-GB90]	[13]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Saxagliptin caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[11]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Ferrosoferric oxide	E00231	14789	Colorant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Saxagliptin Hydrochloride eq 2.5mg base tablet	eq 2.5mg base	Tablet	Oral
Saxagliptin Hydrochloride eq 5mg base tablet	eq 5mg base	Tablet	Oral
Saxagliptin 2.5 mg tablet	2.5 mg	Oral Tablet	Oral
Saxagliptin 5 mg tablet	5 mg	Oral Tablet	Oral

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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: 6316).
2	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6	Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14.
7	Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88.
8	Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
9	Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102.
10	Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J Med Chem. 2011 Jan 27;54(2):510-24.
11	Product Information. Onglyza (saxagliptin). Bristol-Myers Squibb, Princeton, NJ.
12	Cerner Multum, Inc. "Australian Product Information.".
13	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
15	Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
16	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
17	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
18	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
19	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
20	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
21	Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
22	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.