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Compound Detail

CHEMBL3891221

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O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3)cc12

Basic Information

ChEMBL ID CHEMBL3891221
Phase Preclinical
Structure Type MOL
InChI Key FHQXLWCFSUSXBF-UHFFFAOYSA-N
7
Targets
19
Activities
3
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

341.8
MW (Da)
4.56
ALogP
2
HBA
3
HBD
73.3
PSA (Ų)
0.65
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C19H16ClNO3
MW 341.79
Aromatic Rings 3
Heavy Atoms 24
NP-Likeness 0.15

Activity Summary

EC50 14 meas. best 8.72
Kd 3 meas. best 8.05
IC50 2 meas. best 6.4

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1
CHEMBL2111345
EC50 8.72 8.2314 1.9 7
AMP-activated protein kinase, AMPK
CHEMBL2096907
EC50 8.38 7.67 4.2 2
AMPK alpha2/beta1/gamma1
CHEMBL3038455
EC50 8.17 8.06 6.8 2
5'-AMP-activated protein kinase catalytic subunit alpha-1/beta-1/gamma-1
CHEMBL3885503
EC50 8.15 8.15 7.0 1
Unchecked
CHEMBL612545
EC50 8.15 6.865 7.0 2
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1
CHEMBL2111345
Kd 8.05 8.05 9.0 3
5'-AMP-activated protein kinase subunit beta-1
CHEMBL3847
IC50 6.4 6.4 400.0 1
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
CHEMBL241
IC50 4.85 4.85 14000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 744.0 ng.hr.mL-1 Rattus norvegicus
AUC 329.0 ng.hr.mL-1 Rattus norvegicus
AUC 1880.0 ng.hr.mL-1 Rattus norvegicus
AUC 10500.0 ng.hr.mL-1 Rattus norvegicus
AUC 631.0 ng.hr.mL-1 Canis lupus familiaris
AUC 4020.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1970.0 ng.hr.mL-1 Macaca fascicularis
AUC 2690.0 ng.hr.mL-1 Macaca fascicularis
AUC 744.0 ng.hr.mL-1 Rattus norvegicus
AUC 1970.0 ng.hr.mL-1 Macaca fascicularis
CL 22.6 mL.min-1.kg-1 Rattus norvegicus
CL 12.9 mL.min-1.kg-1 Canis lupus familiaris
CL 8.57 mL.min-1.kg-1 Macaca fascicularis
CL 492.0 mL.min-1.g-1 Rattus norvegicus
CL 19.5 mL.min-1.g-1 Macaca mulatta
CL 18.5 mL.min-1.g-1 Homo sapiens
CL 55.0 mL.min-1.kg-1 Macaca fascicularis
CL 54.0 mL.min-1.kg-1 Canis lupus familiaris
CL 849.0 mL.min-1.kg-1 Rattus norvegicus
CL 2.48 mL.min-1.kg-1 Macaca fascicularis
CL 2.82 mL.min-1.kg-1 Canis lupus familiaris
CL 7.64 mL.min-1.kg-1 Rattus norvegicus
CL 22.6 mL.min-1.kg-1 Rattus norvegicus
CL 22.6 mL.min-1.kg-1 Rattus norvegicus
CL 8.57 mL.min-1.kg-1 Macaca fascicularis
Cmax 321.84 nM Rattus norvegicus
Cmax 5558.97 nM Rattus norvegicus
Cmax 11761.61 nM Rattus norvegicus
Cmax 3803.51 nM Canis lupus familiaris
Cmax 2144.59 nM Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 1.9 nM 8.72 Activation of full-length recombinant N-terminal His-tagged human AMPKalpha1beta... 30036059
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 3.3 nM 8.48 Activation of recombinant human AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS... 27490827
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 4.2 nM 8.38 Activation of full length human phosphorylated His-tagged AMPK alpha1/beta1/gamm... 27727125
AMP-activated protein kinase, AMPK EC50 = 4.2 nM 8.38 33P-Based Assay: The biochemical EC50 (half-maximal concentration required for f... -
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 5.6 nM 8.25 Allosteric activation of human AMPK alpha1/beta1/gamma1 by TR-FRET assay 29466005
AMPK alpha2/beta1/gamma1 EC50 = 6.8 nM 8.17 Activation of recombinant human AMPK alpha2/beta1/gamma1 using Cy5-labelled SAMS... 27490827
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 7.0 nM 8.15 Activation of recombinant human AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS... 27490827
5'-AMP-activated protein kinase catalytic subunit alpha-1/beta-1/gamma-1 EC50 = 7.0 nM 8.15 Activation of recombinant rat AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS a... 27490827
Unchecked EC50 = 7.0 nM 8.15 Activation of rat hepatocytes AMPK alpha1/beta1/gamma1 expressed in baculovirus ... 31930920
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 8.2 nM 8.09 Activation of recombinant human AMPK alpha1/beta1/gamma1 assessed as protection ... 27490827
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 Kd = 9.0 nM 8.05 Binding affinity to recombinant human AMPK alpha1/beta1/gamma1 by SPR binding as... 27490827
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 Kd = 9.0 nM 8.05 Binding affinity to human BAP-tagged AMPK alpha1/beta1/gamma1 by SPR assay 29466005
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 Kd = 8.96 nM 8.05 Binding affinity to Bap-tagged human AMPKalpha1beta1gamma1 expressed in Escheric... 30036059
AMPK alpha2/beta1/gamma1 EC50 = 11.3 nM 7.95 Activation of full-length recombinant N-terminal His-tagged human AMPKalpha2beta... 30036059
AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 EC50 = 28.2 nM 7.55 Activation of recombinant human BAP-tagged AMPK alpha1/beta1/gamma1 assessed as ... 27490827
AMP-activated protein kinase, AMPK EC50 = 110.0 nM 6.96 Activation of AMPK in cryopreserved human hepatocytes assessed as increase in ph... 30036059
5'-AMP-activated protein kinase subunit beta-1 IC50 = 400.0 nM 6.4 Activation of recombinant AMPKbeta1 in cryopreserved human hepatocytes assessed ... 30036059
Unchecked EC50 = 2600.0 nM 5.58 Activation of AMPK in African green monkey Vero cells infected with Zika virus P... 31549836
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A IC50 = 14000.0 nM 4.85 Inhibition of PDE3A (unknown origin) 27490827

Literature References

PubMed DOI Target Context # Activities
27490827 10.1021/acs.jmedchem.6b00866 ADMET 55
27490827 10.1021/acs.jmedchem.6b00866 AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 11
30036059 10.1021/acs.jmedchem.8b00807 ADMET 8
27490827 10.1021/acs.jmedchem.6b00866 NON-PROTEIN TARGET 7
30036059 10.1021/acs.jmedchem.8b00807 AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 6
29466005 10.1021/acs.jmedchem.7b01641 ADMET 6
30036059 10.1021/acs.jmedchem.8b00807 Rattus norvegicus 5
27490827 10.1021/acs.jmedchem.6b00866 No relevant target 4
30036059 10.1021/acs.jmedchem.8b00807 Cynomolgus monkey 4
27490827 10.1021/acs.jmedchem.6b00866 Rattus norvegicus 4
29466005 10.1021/acs.jmedchem.7b01641 Rattus norvegicus 3
29466005 10.1021/acs.jmedchem.7b01641 Plasma 3
29466005 10.1021/acs.jmedchem.7b01641 AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 3
27727125 10.1016/j.bmcl.2016.09.065 AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 2
29466005 10.1021/acs.jmedchem.7b01641 Organic anion transporter 3 2
27490827 10.1021/acs.jmedchem.6b00866 5-hydroxytryptamine receptor 2B 2
27490827 10.1021/acs.jmedchem.6b00866 5'-AMP-activated protein kinase catalytic subunit alpha-1/beta-1/gamma-1 2
27490827 10.1021/acs.jmedchem.6b00866 AMPK alpha2/beta1/gamma1 2
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
29466005 10.1021/acs.jmedchem.7b01641 Canis familiaris 2

Data from ChEMBL 36 via Core Engine