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Compound Detail

CHEMBL3915620

LY2881835
Phase I
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Phase I
CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1

Basic Information

ChEMBL ID CHEMBL3915620
Name LY2881835
Phase Phase I
Structure Type MOL
InChI Key FHRWHNJJQGSCQC-LJAQVGFWSA-N

Known Names

LY-2881835 Ly2881835
3
Targets
13
Activities
3
Assay Types
27
PK Parameters
20
Publications
2
Known Names
1
Indications
1
Mechanisms

Molecular Properties

491.6
MW (Da)
6.41
ALogP
3
HBA
1
HBD
49.8
PSA (Ų)
0.37
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Extended Properties

Molecular Formula C33H33NO3
MW 491.63
Aromatic Rings 3
Heavy Atoms 37
NP-Likeness 0.02

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Free fatty acid receptor 1 agonist AGONIST Free fatty acid receptor 1

Indications

Diabetes Mellitus, Type 2

Activity Summary

EC50 10 meas. best 9.07
Ki 2 meas. best 8.33
Kd 1 meas. best 8.6

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Free fatty acid receptor 1
CHEMBL5411
EC50 9.07 9.07 0.8 1
Free fatty acid receptor 1
CHEMBL4422
EC50 8.92 7.655 1.2 8
Free fatty acid receptor 1
CHEMBL1795180
EC50 8.7 8.7 2.0 1
Free fatty acid receptor 1
CHEMBL4422
Kd 8.6 8.6 2.5 1
Free fatty acid receptor 1
CHEMBL4422
Ki 8.33 8.33 4.7 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 5150.0 ng.hr.mL-1 Mus musculus
AUC 218.0 ng.hr.mL-1 Mus musculus
CL 11.0 L/hr Homo sapiens
CL 20.4 mL.min-1.kg-1 Mus musculus
CL 11.6 mL.min-1.kg-1 Rattus norvegicus
CL 4.9 mL.min-1.kg-1 Canis lupus familiaris
Cmax 5797.04 nM Mus musculus
Cmax 2243.56 nM Mus musculus
Cmax 22781.36 nM Rattus norvegicus
Cmax 5817.38 nM Canis lupus familiaris
F 64.0 % Rattus norvegicus
F 71.0 % Mus musculus
F 74.0 % Canis lupus familiaris
T1/2 0.3 hr Homo sapiens
T1/2 1.3 hr Mus musculus
T1/2 0.03333 hr Mus musculus
T1/2 2.1 hr Mus musculus
T1/2 2.1 hr Rattus norvegicus
T1/2 5.05 hr Canis lupus familiaris
T1/2 2.0 hr Rattus norvegicus
T1/2 2.0 hr Mus musculus
T1/2 2.0 hr Canis lupus familiaris
Tmax 0.7 hr Mus musculus
Tmax 0.5 hr Mus musculus
Tmax 0.25 hr Rattus norvegicus
Tmax 3.0 hr Canis lupus familiaris
Vd 111.0 l Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Free fatty acid receptor 1 EC50 = 0.85 nM 9.07 Agonist activity at Prolink-tagged mouse GPR40 fused with EA-tagged beta-arresti... 27749056
Free fatty acid receptor 1 EC50 = 1.2 nM 8.92 Agonist activity at human recombinant full length GPR40 overexpressed in human H... 27749056
Free fatty acid receptor 1 EC50 = 2.0 nM 8.7 Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin ... 27749056
Free fatty acid receptor 1 Kd = 2.5 nM 8.6 Displacement of [3H]-(S)-2-(6-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)bip... 27749056
Free fatty acid receptor 1 Ki = 4.7 nM 8.33 Competitive displacement of [3H]-TAK-875 from full length human recombinant GPR4... 29236497
Free fatty acid receptor 1 Ki = 4.7 nM 8.33 Displacement of [3H]-TAK-875 from human recombinant full-length GPR40 expressed ... 27749056
Free fatty acid receptor 1 EC50 = 8.7 nM 8.06 Agonist activity at human recombinant full-length Prolink-tagged GPR40 fused wit... 27749056
Free fatty acid receptor 1 EC50 = 9.0 nM 8.05 Agonist activity at FFA1 (unknown origin) 36343410
Free fatty acid receptor 1 EC50 = 9.1 nM 8.04 Agonist activity at human GPR40 receptor expressed in HEK293 cells assessed as i... 29236497
Free fatty acid receptor 1 EC50 = 9.1 nM 8.04 Agonist activity at human recombinant full length GPR40 overexpressed in human H... 27749056
Free fatty acid receptor 1 EC50 = 134.0 nM 6.87 Agonist activity at human GPR40 expressed in HEK293 cells assessed as increase i... 29705709
Free fatty acid receptor 1 EC50 = 233.0 nM 6.63 Agonist activity at FFA1 receptor (unknown origin) 27647366
Free fatty acid receptor 1 EC50 = 233.0 nM 6.63 Agonist activity at human GPR40 expressed in HEK293 cells assessed as increase i... 27825762

Literature References

PubMed DOI Target Context # Activities
27749056 10.1021/acs.jmedchem.6b00892 ADMET 40
27749056 10.1021/acs.jmedchem.6b00892 Free fatty acid receptor 1 19
29236497 10.1021/acs.jmedchem.7b01411 ADMET 12
27749056 10.1021/acs.jmedchem.6b00892 No relevant target 6
29705709 10.1016/j.ejmech.2018.04.023 ADMET 6
27749056 10.1021/acs.jmedchem.6b00892 Rattus norvegicus 4
29705709 10.1016/j.ejmech.2018.04.023 Mus musculus 4
29236497 10.1021/acs.jmedchem.7b01411 Unchecked 3
29236497 10.1021/acs.jmedchem.7b01411 No relevant target 3
29236497 10.1021/acs.jmedchem.7b01411 Free fatty acid receptor 1 3
27749056 10.1021/acs.jmedchem.6b00892 Mus musculus 3
27749056 10.1021/acs.jmedchem.6b00892 Peroxisome proliferator-activated receptor alpha 3
27749056 10.1021/acs.jmedchem.6b00892 Peroxisome proliferator-activated receptor delta 3
29236497 10.1021/acs.jmedchem.7b01411 Rattus norvegicus 2
29236497 10.1021/acs.jmedchem.7b01411 Homo sapiens 2
27749056 10.1021/acs.jmedchem.6b00892 Voltage-gated inwardly rectifying potassium channel KCNH2 2
27749056 10.1021/acs.jmedchem.6b00892 RXR alpha/PPAR gamma 2
29705709 10.1016/j.ejmech.2018.04.023 Free fatty acid receptor 1 1
36343410 10.1016/j.ejmech.2022.114883 Free fatty acid receptor 1 1
27647366 10.1016/j.bmc.2016.09.004 Free fatty acid receptor 1 1

Data from ChEMBL 36 via Core Engine