| Bioactivity | Linagliptin is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM. | ||||||||||||
| Target | IC50: 1 nM (DPP-4) | ||||||||||||
| Invitro | Linagliptin inhibits DPP-4 activity in vitro in several independent experiments with IC50 values of 0.4, 0.5, 0.9, and 1.1 nM (mean IC50, approximately 1 nM). Linagliptin inhibits FAP with an IC50 of 89 nM (approximately 90-fold selectivity versus DPP-4)[2]. | ||||||||||||
| In Vivo | In male Wistar rats, Beagle dogs, and Rhesus monkeys, xanthine linagliptin proves to be a highly efficacious, long-lasting, and potent DPP-4 inhibitor providing >70% inhibition for >7 h for all three species after oral administration of 1 mg/kg. Single oral administration of linagliptin to db/db mice 45 min prior to an oral glucose tolerance test reduced plasma glucose excursion in a dose-dependent manner from 0.1 mg/kg (15% inhibition) to 1 mg/kg (66% inhibition)[1]. Linagliptin (3 and 10 mg/kg) dose-dependently inhibits the DPP-4 enzyme in plasma within 30 min of administration. Linagliptin (1 mg/kg, p.o.) significantly reduces glucose excursion by approximately 50%[2]. Oral administration of the DPP-4 inhibitor linagliptin (3 mg/kg, p.o.) strongly reduces DPP-4 activity, stabilizes active GLP-1 in chronic wounds, and improves healing in ob/ob mice. At day 10 postwounding, linagliptin-treated ob/ob mice show largely epithelialized wounds characterized by the absence of neutrophils[3]. | ||||||||||||
| Name | Linagliptin | ||||||||||||
| CAS | 668270-12-0 | ||||||||||||
| Formula | C25H28N8O2 | ||||||||||||
| Molar Mass | 472.54 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Eckhardt M, et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 d [2]. Thomas L, et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action [3]. Schurmann C, et al. The dipeptidyl peptidase-4 inhibitor linagliptin attenuates inflammation and accelerates epithelialization in wounds of diabetic ob/ob mice. J Pharmacol Exp Ther. 2012 Jul;342(1):71-80. [4]. Huan Y, et al. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Sci Rep. 2017 Jun 28;7(1):4351. |