Saxagliptin

Saxagliptin
Clinical data
Trade names	Onglyza
Other names	BMS-477118
AHFS/Drugs.com	Professional Drug Facts
MedlinePlus	a610003
License data	EU EMA: by INN; US DailyMed: Saxagliptin; US FDA: Saxagliptin;
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth (tablets)
Drug class	DPP-4 inhibitors
ATC code	A10BH03 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	~75% (Tmax = 2 h)
Protein binding	negligible
Metabolism	Liver (CYP3A4 and CYP3A5)
Elimination half-life	2.5 h (saxagliptin), 3.1 h (main metabolite)
Excretion	22% (Bile duct), 75% (Urine)
Identifiers
	IUPAC name (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile;
CAS Number	HCl: 709031-78-7 ;
PubChem CID	11243969; HCl: 49800073;
IUPHAR/BPS	6316;
DrugBank	DB06335 ;
ChemSpider	9419005 ;
UNII	9GB927LAJW; HCl: Z8J84YIX6L ;
KEGG	D08996; HCl: D10262;
ChEBI	CHEBI:71272;
ChEMBL	ChEMBL385517 ; HCl: ChEMBL1201743;
CompTox Dashboard (EPA)	DTXSID7048580 ;
Chemical and physical data
Formula	C18H25N3O2
Molar mass	315.417 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N1[C@H](C#N)C[C@@H]2C[C@H]12)[C@@H](N)C35CC4CC(C3)CC(O)(C4)C5;
	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 ; Key:QGJUIPDUBHWZPV-SGTAVMJGSA-N ;
	(what is this?) (verify)

Saxagliptin, sold under the brand name Onglyza, is an oral hypoglycemic (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class.^[1]^[2] Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug.

In April 2016, the U.S. FDA added a warning about increased risk of heart failure.^[3] This was based on data in an article that concluded "DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes."^[4]

^ Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, et al. (July 2005). "Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes". Journal of Medicinal Chemistry. 48 (15): 5025–5037. doi:10.1021/jm050261p. PMID 16033281.
^ "Bristol, Takeda Drugs Offer Alternatives to Januvia (Update2)". Bloomberg. 2008-06-07.
^ "Safety Alerts for Human Medical Products - Diabetes Medications Containing Saxagliptin and Alogliptin: Drug Safety Communication - Risk of Heart Failure". www.fda.gov. Retrieved 7 April 2016.
^ Cite error: The named reference Sci2013 was invoked but never defined (see the help page).

[ahren-1] Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, et al. (July 2005). "Discovery and preclinical profile of Saxagliptin (BMS-477118): a highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes". Journal of Medicinal Chemistry. 48 (15): 5025–5037. doi:10.1021/jm050261p. PMID 16033281.

[Bloomberg-2] "Bristol, Takeda Drugs Offer Alternatives to Januvia (Update2)". Bloomberg. 2008-06-07.

[3] "Safety Alerts for Human Medical Products - Diabetes Medications Containing Saxagliptin and Alogliptin: Drug Safety Communication - Risk of Heart Failure". www.fda.gov. Retrieved 7 April 2016.

[Sci2013-4] Cite error: The named reference Sci2013 was invoked but never defined (see the help page).

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