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Compound Detail

CHEMBL237500

LINAGLIPTIN
💊 Approved Drug
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💊 Approved Drug
CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1c(=O)n(Cc1nc(C)c3ccccc3n1)c(=O)n2C

Basic Information

ChEMBL ID CHEMBL237500
Name LINAGLIPTIN
Phase Approved
Structure Type MOL
InChI Key LTXREWYXXSTFRX-QGZVFWFLSA-N
Therapeutic ✓ Yes

Known Names

BI 1356 BI 1356 BS BI-1356 BI-1356-BS BI-1356BS BI1356 BS 1356 BS BS-1356-BS Linagliptin Linagliptin component of glyxambi Linagliptin component of jentadueto Linagliptin component of trijardy xr +5 more
10
Targets
45
Activities
3
Assay Types
16
PK Parameters
20
Publications
17
Known Names
11
Indications
1
Mechanisms

Molecular Properties

472.6
MW (Da)
1.15
ALogP
10
HBA
1
HBD
116.9
PSA (Ų)
0.44
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2011
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -gliptin
USAN Year 2009

Extended Properties

Molecular Formula C25H28N8O2
MW 472.55
Aromatic Rings 4
Heavy Atoms 35
NP-Likeness -1.31

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dipeptidyl peptidase IV inhibitor INHIBITOR Dipeptidyl peptidase 4

Indications

Diabetes Mellitus Diabetes Mellitus, Type 2 Respiratory Tract Diseases Severe Acute Respiratory Syndrome Adenocarcinoma Carcinoma, Non-Small-Cell Lung Esophageal Neoplasms Hypertension Renal Insufficiency Schizophrenia Stomach Neoplasms

ATC Classification

A10BH05
linagliptin
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: DRUGS USED IN DIABETES

Activity Summary

IC50 42 meas. best 10.0
Kd 2 meas. best 8.28
EC50 1 meas. best 8.51

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Dipeptidyl peptidase 4
CHEMBL284
IC50 10.0 9.0973 0.1 26
Dipeptidyl peptidase 4
CHEMBL3883
IC50 9.92 9.92 0.1 1
Dipeptidyl peptidase 4
CHEMBL284
EC50 8.51 8.51 3.1 1
Dipeptidyl peptidase 4
CHEMBL284
Kd 8.28 8.28 5.3 1
Prolyl endopeptidase FAP
CHEMBL4683
IC50 7.15 6.92 70.8 4
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 6.53 6.5267 295.0 3
Prolyl endopeptidase FAP
CHEMBL5769
IC50 6.43 6.43 370.0 2
Dipeptidyl peptidase 8
CHEMBL4657
IC50 4.4 4.4 40000.0 1
POU domain, class 2, transcription factor 1
CHEMBL3509601
IC50 4.39 4.37 41000.0 2
ADMET
CHEMBL612558
IC50 4.18 4.18 66100.0 1
POU domain, class 2, transcription factor 2
CHEMBL3509582
IC50 4.1 4.1 80000.0 1
Dipeptidyl peptidase 9
CHEMBL4793
IC50 4.0 4.0 100000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 87.42 ng.hr.mL-1 Rattus norvegicus
CL 37.3 mL.min-1.kg-1 Rattus norvegicus
CL 15.8 mL.min-1.kg-1 Macaca fascicularis
CL 34.0 mL.min-1.kg-1 Rattus norvegicus
CL 2.7 % Mus musculus
CL 24.2 % Mus musculus
Cmax 21.0 nM Rattus norvegicus
Cmax 10.0 nM Homo sapiens
F 50.7 % Rattus norvegicus
F 50.1 % Macaca fascicularis
F 9.0 % Rattus norvegicus
MRT 14.3 hr Rattus norvegicus
MRT 17.4 hr Macaca fascicularis
T1/2 35.9 hr Rattus norvegicus
T1/2 41.4 hr Macaca fascicularis
T1/2 10.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Dipeptidyl peptidase 4 IC50 = 0.1 nM 10.0 Inhibition of human C-terminal step-tagged DPP4 expressed using baculovirus syst... 22177783
Dipeptidyl peptidase 4 IC50 = 0.1 nM 10.0 Inhibition of human DPP4 preincubated for 30 mins followed by Gly-Pro-AMC additi... 27190600
Dipeptidyl peptidase 4 IC50 = 0.12 nM 9.92 Inhibition of mouse DPP-4 using Gly-Pro-AMC as substrate measured after 5 mins b... 37647598
Dipeptidyl peptidase 4 IC50 = 0.14 nM 9.85 Inhibition of human recombinant DPP-4 (1 to 530 residues) using Gly-Pro-AMC as s... 37647598
Dipeptidyl peptidase 4 IC50 = 0.21 nM 9.68 DPP-IV Activity Inhibition Tests In Vitro: DPP-IV could hydrolyze Gly-Pro-Aminol... -
Dipeptidyl peptidase 4 IC50 = 0.4 nM 9.4 Inhibition of human DPP4 using Gly-Pro-AMC as substrate incubated for 30 mins by... 36209967
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 DPP-IV Assay: 50 μl substrate solution (AFC; AFC is amido-4-trifluoromethylcouma... -
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP4 in human Caco2 cells using H-Ala-Pro-7-amido-4-trifluoromethy... 23623674
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of human DPP4 -
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP4 in human plasma using Gly-Pro-AMC as substrate by fluorimetri... 22938786
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP4 in human Caco-2 cells after 1 hr 18485703
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of human DPP4 in Caco-2 cells by fluorescene assay 18052023
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 DPP-IV Activity InhibitoryAssay: Gly-Pro-7-amido-4-methylcoumarin can be hydroly... -
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of human recombinant DPP4 (39 to 766 residues) using Ala-Pro-AFC as s... 27438064
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP4 (unknown origin) 33243532
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP-4 (unknown origin) 37647598
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of human recombinant DPP-4 expressed in human Caco-2 cells using H-Al... 37647598
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Inhibition of DPP4 (unknown origin) 38704940
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 Fluorescence Assay: 50 μl substrate solution (AFC; AFC is amido-4-trifluoromethy... -
Dipeptidyl peptidase 4 IC50 = 1.0 nM 9.0 DPP-IV assay: 50 μl substrate solution (AFC; AFC is amido-4-trifluoromethylcouma... -

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 53
23073734 10.1124/dmd.112.048470 ADMET 23
27438064 10.1021/acs.jmedchem.6b00475 Dipeptidyl peptidase 4 8
18052023 10.1021/jm701280z Rattus norvegicus 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
37647598 10.1021/acs.jmedchem.3c00412 Dipeptidyl peptidase 4 5
18052023 10.1021/jm701280z Cynomolgus monkey 5
23073734 10.1124/dmd.112.048470 POU domain, class 2, transcription factor 2 5
18052023 10.1021/jm701280z No relevant target 4
22177783 10.1016/j.bmcl.2011.11.054 Rattus norvegicus 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 3
22938786 10.1016/j.bmc.2012.07.046 Unchecked 3
27438064 10.1021/acs.jmedchem.6b00475 ADMET 3
23073734 10.1124/dmd.112.048470 POU domain, class 2, transcription factor 1 3
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 3
23073734 10.1124/dmd.112.048470 Solute carrier organic anion transporter family member 1B1 3
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 3
23073734 10.1124/dmd.112.048470 Organic anion transporter 3 3
18052023 10.1021/jm701280z Mus musculus 3
30074791 10.1021/acs.jmedchem.8b00727 Mus musculus 3

Data from ChEMBL 36 via Core Engine