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Compound Detail

CHEMBL4518483

DANUGLIPRON
🧪 Phase II
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🧪 Phase II
N#Cc1ccc(COc2cccc(C3CCN(Cc4nc5ccc(C(=O)O)cc5n4C[C@@H]4CCO4)CC3)n2)c(F)c1

Basic Information

ChEMBL ID CHEMBL4518483
Name DANUGLIPRON
Phase Phase II
Structure Type MOL
InChI Key HYBAKUMPISVZQP-DEOSSOPVSA-N

Known Names

Danuglipron Pf-06882961
5
Targets
30
Activities
3
Assay Types
30
PK Parameters
20
Publications
2
Known Names
4
Indications
1
Mechanisms

Molecular Properties

555.6
MW (Da)
4.89
ALogP
8
HBA
1
HBD
113.5
PSA (Ų)
0.31
QED
1
Ro5 Violations
9
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -glipron
USAN Year 2020

Extended Properties

Molecular Formula C31H30FN5O4
MW 555.61
Aromatic Rings 4
Heavy Atoms 41
NP-Likeness -1.63

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Glucagon-like peptide 1 receptor agonist AGONIST Glucagon-like peptide 1 receptor

Indications

Diabetes Mellitus, Type 2 Obesity Liver Diseases Non-alcoholic Fatty Liver Disease

Activity Summary

EC50 23 meas. best 10.4
IC50 5 meas. best 5.9
Ki 2 meas. best 7.1

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Glucagon-like peptide 1 receptor
CHEMBL1784
EC50 10.4 7.9114 0.0 22
Unchecked
CHEMBL612545
EC50 8.36 8.36 4.4 1
Glucagon-like peptide 1 receptor
CHEMBL1784
Ki 7.1 6.77 80.0 2
Cytochrome P450 2C8
CHEMBL3721
IC50 5.9 5.9 1250.0 1
5-hydroxytryptamine receptor 1A
CHEMBL214
IC50 5.62 5.62 2424.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.58 5.3967 2600.0 3

Pharmacokinetic Data

Parameter Value Units Species
AUC 1240.0 ng.hr.mL-1 Macaca fascicularis
AUC 303.0 ng.hr.mL-1 Macaca fascicularis
AUC 11000.0 ng.hr.mL-1 Macaca fascicularis
AUC 296.0 ng.hr.mL-1 Rattus norvegicus
AUC 168.0 ng.hr.mL-1 Rattus norvegicus
AUC 11900.0 ng.hr.mL-1 Rattus norvegicus
AUC 3383.0 ng.hr.mL-1 Macaca fascicularis
AUC 1100.0 ng.hr.mL-1 Macaca fascicularis
AUC 1670.0 ng.hr.mL-1 Mus musculus
AUC 2280.0 ng.hr.mL-1 Mus musculus
AUC 520.0 ng.hr.mL-1 Rattus norvegicus
AUC 170.0 ng.hr.mL-1 Rattus norvegicus
CL 57.3 mL.min-1.kg-1 Rattus norvegicus
CL 13.8 mL.min-1.kg-1 Macaca fascicularis
CL 5.0 mL.min-1.g-1 Homo sapiens
CL 13.0 mL.min-1.g-1 Rattus norvegicus
CL 13.0 mL.min-1.g-1 Mus musculus
Cmax 5075.5 nM Rattus norvegicus
Cmax 253.78 nM Rattus norvegicus
Cmax 123.65 nM Macaca fascicularis
Cmax 2069.8 nM Macaca fascicularis
Cmax 670.0 nM Macaca fascicularis
Cmax 163000.0 nM Macaca fascicularis
Cmax 5111.5 nM Mus musculus
Cmax 197.98 nM Rattus norvegicus
F 5.0 % Macaca fascicularis
F 9.0 % Macaca fascicularis
F 11.0 % Rattus norvegicus
F 39.0 % Rattus norvegicus
F 3.41 % Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Glucagon-like peptide 1 receptor EC50 = 0.04 nM 10.4 Agonist activity at N-terminal HA-tagged human GLP-1R expressed in HEK293 cells ... 37286364
Glucagon-like peptide 1 receptor EC50 = 0.058 nM 10.24 Agonist activity human GLP-1R stably expressed in HEK293 cells assessed as reduc... 38795571
Glucagon-like peptide 1 receptor EC50 = 0.12 nM 9.92 Agonist activity at human GLP-1R expressed in HEK293 cells assessed as accumulat... 39140772
Glucagon-like peptide 1 receptor EC50 = 0.71 nM 9.15 Agonist activity at human GLP-1R expressed in CHO-K1 cells assessed as cAMP accu... 35647711
Glucagon-like peptide 1 receptor EC50 = 0.71 nM 9.15 Activation of GLP-1R (unknown origin) 38959726
Glucagon-like peptide 1 receptor EC50 = 0.95 nM 9.02 CHO GLP-1R Clone H6-Assay 1: GLP-1R-mediated agonist activity was determined wit... -
Glucagon-like peptide 1 receptor EC50 = 1.1 nM 8.96 CHO GLP-1R Clone H6-Assay 1: GLP-1R-mediated agonist activity was determined wit... -
Glucagon-like peptide 1 receptor EC50 = 1.1 nM 8.96 Agonist activity at GLP-1 receptor (unknown origin) expressed in CHO cells by cA... 37591316
Glucagon-like peptide 1 receptor EC50 = 1.1 nM 8.96 Agonist activity at human GLP-1R expressed in CHO-K1 cells assessed as cAMP accu... 35647711
Unchecked EC50 = 4.4 nM 8.36 Activation of cynomolgus monkey GLP-1R expressed in CHO cells assessed as increa... 35647711
Glucagon-like peptide 1 receptor EC50 = 12.0 nM 7.92 Displacement of [125I]GLP-1 from human GLP-1R (7 to 36 residues) expressed in HE... 31930920
Glucagon-like peptide 1 receptor EC50 = 13.0 nM 7.89 Agonist activity at GLP-1R (unknown origin) expressed in candidate selection CHO... 35647711
Glucagon-like peptide 1 receptor EC50 = 13.0 nM 7.89 Displacement of [125I]-GLP1 from GLP-1 receptor (unknown origin) expressed in CH... 37591316
Glucagon-like peptide 1 receptor EC50 = 13.0 nM 7.89 CHO GLP-1R Clone C6-Assay 2: GLP-1R-mediated agonist activity was determined wit... -
Glucagon-like peptide 1 receptor EC50 = 17.0 nM 7.77 CHO GLP-1R Clone C6-Assay 2: GLP-1R-mediated agonist activity was determined wit... -
Glucagon-like peptide 1 receptor Ki = 80.0 nM 7.1 Displacement of [3H]PF-06883365 from FAP-tagged human GLP-1R expressed in CHO ce... 35647711
Glucagon-like peptide 1 receptor EC50 = 132.0 nM 6.88 Agonist activity at GLP-1R (unknown origin) transfected in HEK293 cells assessed... 38795571
Glucagon-like peptide 1 receptor EC50 = 194.0 nM 6.71 Agonist activity at GLP-1R (unknown origin) transfected in HEK293 cells assessed... 38795571
Glucagon-like peptide 1 receptor EC50 = 230.0 nM 6.64 Agonist activity at FAP-tagged human GLP-1R expressed in HEK293 cells assessed a... 35647711
Glucagon-like peptide 1 receptor Ki = 360.0 nM 6.44 Displacement of [125I]GLP-1 from FAP-tagged human GLP-1R expressed in CHO cells ... 35647711

Literature References

PubMed DOI Target Context # Activities
35647711 10.1021/acs.jmedchem.1c01856 ADMET 30
39140772 10.1021/acs.jmedchem.4c01177 ADMET 29
35647711 10.1021/acs.jmedchem.1c01856 Glucagon-like peptide 1 receptor 18
37286364 10.1021/acs.jmedchem.3c00320 Glucagon-like peptide 1 receptor 9
35647711 10.1021/acs.jmedchem.1c01856 Unchecked 7
37286364 10.1021/acs.jmedchem.3c00320 ADMET 6
38795571 10.1016/j.bmc.2024.117761 Glucagon-like peptide 1 receptor 6
37286364 10.1021/acs.jmedchem.3c00320 Voltage-gated inwardly rectifying potassium channel KCNH2 2
37286364 10.1021/acs.jmedchem.3c00320 Unchecked 2
37591316 10.1016/j.bmcl.2023.129454 Glucagon-like peptide 1 receptor 2
37591316 10.1016/j.bmcl.2023.129454 ADMET 2
38795571 10.1016/j.bmc.2024.117761 Mus musculus 2
39140772 10.1021/acs.jmedchem.4c01177 5-hydroxytryptamine receptor 1A 2
39140772 10.1021/acs.jmedchem.4c01177 Cytochrome P450 3A4 2
35647711 10.1021/acs.jmedchem.1c01856 Cynomolgus monkey 1
35647711 10.1021/acs.jmedchem.1c01856 Mus musculus 1
31930920 10.1021/acs.jmedchem.9b01701 Glucagon-like peptide 1 receptor 1
35647711 10.1021/acs.jmedchem.1c01856 Voltage-gated inwardly rectifying potassium channel KCNH2 1
38959726 10.1016/j.ejmech.2024.116632 Glucagon-like peptide 1 receptor 1
39140772 10.1021/acs.jmedchem.4c01177 Glucagon-like peptide 1 receptor 1

Data from ChEMBL 36 via Core Engine