Linagliptin

Linagliptin is a purine and quinazoline derivative that functions as a potentiator of incretin and as long lasting dipeptidyl-peptidase IV inhibitor. It is used as a hypoglycemic agent in the treatment of Type II diabetes mellitus

General

Type : Drug, Purine, Gliptin, Quinazoline

Chemical_Nomenclature : 8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione. Linagliptin inhibits also fibroblast activation protein (FAP)

Canonical SMILES : CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C

InChI : InChI=1S\/C25H28N8O2\/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20\/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3\/t17-\/m1\/s1

InChIKey : LTXREWYXXSTFRX-QGZVFWFLSA-N

Other name(s) : Tradjenta  ||  BI-1356  ||  Trajenta  ||  Ondero


MW : 472.54

Formula : C25H28N8O2

CAS_number : 668270-12-0

PubChem : 10096344

UniChem : LTXREWYXXSTFRX-QGZVFWFLSA-N

IUPHAR : 6318

Wikipedia : Linagliptin

Target

Families : Linagliptin ligand of proteins in family
DPP4N_Peptidase_S9

Structure :
2RGU 6Y0F

Protein :
human-DPP4 human-FAP

References (24)

Title : Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats - Zakaria_2024_Pharm.Dev.Technol__1
Author(s) : Zakaria EM , El-Gamal SF , Mahmoud SM , El-Nahas HM , El-Bassossy HM
Ref : Pharm Dev Technol , :1 , 2024
Abstract :
PubMedSearch : Zakaria_2024_Pharm.Dev.Technol__1
PubMedID: 39311002

Title : Targeting DPP4-RBD interactions by sitagliptin and linagliptin delivers a potential host-directed therapy against pan-SARS-CoV-2 infections - Mani_2023_Int.J.Biol.Macromol_245_125444
Author(s) : Mani S , Kaur A , Jakhar K , Kumari G , Sonar S , Kumar A , Das S , Kumar S , Kumar V , Kundu R , Pandey AK , Singh UP , Majumdar T
Ref : Int J Biol Macromol , 245 :125444 , 2023
Abstract :
PubMedSearch : Mani_2023_Int.J.Biol.Macromol_245_125444
PubMedID: 37385308
Gene_locus related to this paper: human-DPP4

Title : Linagliptin ameliorated cardiac fibrosis and restored cardiomyocyte structure in diabetic mice associated with the suppression of necroptosis - Adhikari_2023_J.Diabetes.Investig__
Author(s) : Adhikari J , Hirai T , Kawakita E , Iwai K , Koya D , Kanasaki K
Ref : J Diabetes Investig , : , 2023
Abstract :
PubMedSearch : Adhikari_2023_J.Diabetes.Investig__
PubMedID: 37092329

Title : A Quantitative Systems Pharmacology Model of the Incretin Hormones GIP and GLP1, Glucagon, Glucose, Insulin, and the Small Molecule DPP-4 Inhibitor, Linagliptin - Wu_2023_J.Pharm.Sci__
Author(s) : Wu N , An G
Ref : J Pharm Sci , : , 2023
Abstract :
PubMedSearch : Wu_2023_J.Pharm.Sci__
PubMedID: 37716531

Title : The dipeptidyl peptidase-4 inhibitor linagliptin ameliorates LPS-induced acute lung injury by maintenance of pulmonary microvascular barrier via activating the Epac1\/AKT pathway - Zhang_2022_Biomed.Pharmacother_155_113704
Author(s) : Zhang N , Tang S , Zhang J , Pei B , Pang T , Sun G
Ref : Biomed Pharmacother , 155 :113704 , 2022
Abstract :
PubMedSearch : Zhang_2022_Biomed.Pharmacother_155_113704
PubMedID: 36115114

Title : Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal - Listos_2022_Molecules_27_
Author(s) : Listos J , Listos P , Baranowska-Bosiacka I , Karpiuk A , Filarowska J , Lupina M , Slowik T , Zawislak S , Kotlinska J
Ref : Molecules , 27 : , 2022
Abstract :
PubMedSearch : Listos_2022_Molecules_27_
PubMedID: 35458676

Title : Linagliptin, a DPP-4 inhibitor, ameliorates Abeta (1-42) peptides induced neurodegeneration and brain insulin resistance (BIR) via insulin receptor substrate-1 (IRS-1) in rat model of Alzheimer's disease - Siddiqui_2021_Neuropharmacol__108662
Author(s) : Siddiqui N , Ali J , Parvez S , Zameer S , Najmi AK , Akhtar M
Ref : Neuropharmacology , :108662 , 2021
Abstract :
PubMedSearch : Siddiqui_2021_Neuropharmacol__108662
PubMedID: 34119519

Title : The dipeptidyl peptidase 4 inhibitor linagliptin ameliorates renal injury and accelerated resolution in a rat model of crescentic nephritis - Mayer_2021_Br.J.Pharmacol_178_878
Author(s) : Mayer AL , Scheitacker I , Ebert N , Klein T , Amann K , Daniel C
Ref : British Journal of Pharmacology , 178 :878 , 2021
Abstract :
PubMedSearch : Mayer_2021_Br.J.Pharmacol_178_878
PubMedID: 33171531

Title : A Single Second Shell Amino Acid Determines Affinity and Kinetics of Linagliptin Binding to Type 4 Dipeptidyl Peptidase and Fibroblast Activation Protein - Schnapp_2021_ChemMedChem_16_630
Author(s) : Schnapp G , Hoevels Y , Bakker RA , Schreiner P , Klein T , Nar H
Ref : ChemMedChem , 16 :630 , 2021
Abstract :
PubMedSearch : Schnapp_2021_ChemMedChem_16_630
PubMedID: 33030297
Gene_locus related to this paper: human-FAP

Title : Metformin dose increase versus added linagliptin in non-alcoholic fatty liver disease and type 2 diabetes: An analysis of the J-LINK study - Komorizono_2021_Diabetes.Obes.Metab_23_832
Author(s) : Komorizono Y , Hosoyamada K , Imamura N , Kajiya S , Hashiguchi Y , Ueyama N , Shinmaki H , Koriyama N , Tsukasa M , Kamada T
Ref : Diabetes Obes Metab , 23 :832 , 2021
Abstract :
PubMedSearch : Komorizono_2021_Diabetes.Obes.Metab_23_832
PubMedID: 33236464

Title : A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice - Berger_2018_Endocrinol.Diabetes.Metab_1_e00002
Author(s) : Berger JP , SinhaRoy R , Pocai A , Kelly TM , Scapin G , Gao YD , Pryor KAD , Wu JK , Eiermann GJ , Xu SS , Zhang X , Tatosian DA , Weber AE , Thornberry NA , Carr RD
Ref : Endocrinol Diabetes Metab , 1 :e00002 , 2018
Abstract :
PubMedSearch : Berger_2018_Endocrinol.Diabetes.Metab_1_e00002
PubMedID: 30815539
Gene_locus related to this paper: human-DPP4

Title : Pharmacokinetic and pharmacodynamic evaluation of linagliptin for the treatment of type 2 diabetes mellitus, with consideration of Asian patient populations - Ceriello_2017_J.Diabetes.Investig_8_19
Author(s) : Ceriello A , Inagaki N
Ref : J Diabetes Investig , 8 :19 , 2017
Abstract :
PubMedSearch : Ceriello_2017_J.Diabetes.Investig_8_19
PubMedID: 27180612

Title : Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes - Jojima_2016_Diabetol.Metab.Syndr_8_45
Author(s) : Jojima T , Tomotsune T , Iijima T , Akimoto K , Suzuki K , Aso Y
Ref : Diabetol Metab Syndr , 8 :45 , 2016
Abstract :
PubMedSearch : Jojima_2016_Diabetol.Metab.Syndr_8_45
PubMedID: 27462372

Title : Long-Term Efficacy and Safety of Linagliptin in Patients With Type 2 Diabetes and Severe Renal Impairment: A 1-year, randomized, double-blind, placebo-controlled study - McGill_2013_Diabetes.Care_36_237
Author(s) : McGill JB , Sloan L , Newman J , Patel S , Sauce C , von Eynatten M , Woerle HJ
Ref : Diabetes Care , 36 :237 , 2013
Abstract :
PubMedSearch : McGill_2013_Diabetes.Care_36_237
PubMedID: 23033241

Title : Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase-4 inhibitor linagliptin: a 4-week multicenter, randomized, double-blind, placebo-controlled phase IIa study in Japanese type 2 diabetes patients - Horie_2011_Clin.Ther_33_973
Author(s) : Horie Y , Kanada S , Watada H , Sarashina A , Taniguchi A , Hayashi N , Graefe-Mody EU , Woerle HJ , Dugi KA
Ref : Clin Ther , 33 :973 , 2011
Abstract :
PubMedSearch : Horie_2011_Clin.Ther_33_973
PubMedID: 21723606

Title : Assessment of the pharmacokinetic interaction between the novel DPP-4 inhibitor linagliptin and a sulfonylurea, glyburide, in healthy subjects - Graefe-Mody_2011_Drug.Metab.Pharmacokinet_26_123
Author(s) : Graefe-Mody U , Rose P , Ring A , Zander K , Iovino M , Woerle HJ
Ref : Drug Metab Pharmacokinet , 26 :123 , 2011
Abstract :
PubMedSearch : Graefe-Mody_2011_Drug.Metab.Pharmacokinet_26_123
PubMedID: 21084763

Title : The dipeptidyl peptidase-4 inhibitor linagliptin exhibits time- and dose-dependent localization in kidney, liver, and intestine after intravenous dosing: results from high resolution autoradiography in rats - Greischel_2010_Drug.Metab.Dispos_38_1443
Author(s) : Greischel A , Binder R , Baierl J
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 38 :1443 , 2010
Abstract :
PubMedSearch : Greischel_2010_Drug.Metab.Dispos_38_1443
PubMedID: 20538719

Title : Pharmacokinetics and pharmacodynamics of single rising intravenous doses (0.5 mg-10 mg) and determination of absolute bioavailability of the dipeptidyl peptidase-4 inhibitor linagliptin (BI 1356) in healthy male subjects - Retlich_2010_Clin.Pharmacokinet_49_829
Author(s) : Retlich S , Duval V , Ring A , Staab A , Huttner S , Jungnik A , Jaehde U , Dugi KA , Graefe-Mody U
Ref : Clinical Pharmacokinetics , 49 :829 , 2010
Abstract :
PubMedSearch : Retlich_2010_Clin.Pharmacokinet_49_829
PubMedID: 21053992

Title : The metabolism and disposition of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, in humans - Blech_2010_Drug.Metab.Dispos_38_667
Author(s) : Blech S , Ludwig-Schwellinger E , Grafe-Mody EU , Withopf B , Wagner K
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 38 :667 , 2010
Abstract :
PubMedSearch : Blech_2010_Drug.Metab.Dispos_38_667
PubMedID: 20086031

Title : Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes - Forst_2010_Diabet.Med_27_1409
Author(s) : Forst T , Uhlig-Laske B , Ring A , Graefe-Mody U , Friedrich C , Herbach K , Woerle HJ , Dugi KA
Ref : Diabet Med , 27 :1409 , 2010
Abstract :
PubMedSearch : Forst_2010_Diabet.Med_27_1409
PubMedID: 21059094

Title : Evaluation of the pharmacokinetic interaction between the dipeptidyl peptidase-4 inhibitor linagliptin and pioglitazone in healthy volunteers - Graefe-Mody_2010_Int.J.Clin.Pharmacol.Ther_48_652
Author(s) : Graefe-Mody EU , Jungnik A , Ring A , Woerle HJ , Dugi KA
Ref : Int J Clinical Pharmacology & Therapeutics , 48 :652 , 2010
Abstract :
PubMedSearch : Graefe-Mody_2010_Int.J.Clin.Pharmacol.Ther_48_652
PubMedID: 20875371

Title : Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients - Heise_2009_Diabetes.Obes.Metab_11_786
Author(s) : Heise T , Graefe-Mody EU , Huttner S , Ring A , Trommeshauser D , Dugi KA
Ref : Diabetes Obes Metab , 11 :786 , 2009
Abstract :
PubMedSearch : Heise_2009_Diabetes.Obes.Metab_11_786
PubMedID: 19476474

Title : Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI 1356)--investigations in DPP-4 deficient and wildtype rats - Retlich_2009_Biopharm.Drug.Dispos_30_422
Author(s) : Retlich S , Withopf B , Greischel A , Staab A , Jaehde U , Fuchs H
Ref : Biopharmaceutics & Drug Disposition , 30 :422 , 2009
Abstract :
PubMedSearch : Retlich_2009_Biopharm.Drug.Dispos_30_422
PubMedID: 19771584

Title : 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylme thyl)-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 diabetes - Eckhardt_2007_J.Med.Chem_50_6450
Author(s) : Eckhardt M , Langkopf E , Mark M , Tadayyon M , Thomas L , Nar H , Pfrengle W , Guth B , Lotz R , Sieger P , Fuchs H , Himmelsbach F
Ref : Journal of Medicinal Chemistry , 50 :6450 , 2007
Abstract :
PubMedSearch : Eckhardt_2007_J.Med.Chem_50_6450
PubMedID: 18052023
Gene_locus related to this paper: human-DPP4