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Compound Detail

CHEMBL3819587

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COc1cc([C@@H](CC(=O)O)c2ccc(C)c(CN3C[C@@H](C)Oc4ccccc4S3(=O)=O)c2)cc2nnn(C)c12

Basic Information

ChEMBL ID CHEMBL3819587
Phase Preclinical
Structure Type MOL
InChI Key ZDNGJXBUEQNFBQ-GCJKJVERSA-N
5
Targets
14
Activities
4
Assay Types
2
PK Parameters
20
Publications
0
Known Names

Molecular Properties

550.6
MW (Da)
3.86
ALogP
8
HBA
1
HBD
123.8
PSA (Ų)
0.37
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C28H30N4O6S
MW 550.64
Aromatic Rings 4
Heavy Atoms 39
NP-Likeness -0.63

Activity Summary

EC50 6 meas. best 7.92
IC50 4 meas. best 8.1
Kd 3 meas. best 8.89
Ki 1 meas. best 9.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Kelch-like ECH-associated protein 1
CHEMBL2069156
Ki 9.0 9.0 1.0 1
Kelch-like ECH-associated protein 1
CHEMBL2069156
Kd 8.89 8.8767 1.3 3
Kelch-like ECH-associated protein 1
CHEMBL2069156
IC50 8.1 8.1 8.0 1
Keap1/Nrf2
CHEMBL3038498
EC50 7.92 7.678 12.0 5
Kelch-like ECH-associated protein 1
CHEMBL2069156
EC50 5.72 5.72 1900.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 5.6 5.6 2500.0 1
Bile salt export pump
CHEMBL6020
IC50 5.4 5.4 4000.0 1
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
CHEMBL241
IC50 5.0 5.0 10000.0 1

Pharmacokinetic Data

Parameter Value Units Species
F 7.0 % Rattus norvegicus
Ka 1.1 10'6/M/s Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Kelch-like ECH-associated protein 1 Ki = 1.0 nM 9.0 Inhibition of Cys5-LDEETGEFL-NH2 binding to recombinant human KEAP1 Kelch domain... 31411465
Kelch-like ECH-associated protein 1 Kd = 1.3 nM 8.89 Binding affinity to human recombinant N-terminal His6 and Avi-tagged KEAP1 (321 ... 27031670
Kelch-like ECH-associated protein 1 Kd = 1.3 nM 8.89 Binding affinity to KEAP1 (unknown origin) by isothermal titration calorimetry 38621319
Kelch-like ECH-associated protein 1 Kd = 1.4 nM 8.85 Binding affinity to recombinant human KEAP1 Kelch domain (321 to 609 residues) e... 31411465
Kelch-like ECH-associated protein 1 IC50 = 8.0 nM 8.1 Inhibition of Cys5-LDEETGEFL-NH2 binding to recombinant human KEAP1 Kelch domain... 31411465
Keap1/Nrf2 EC50 = 12.0 nM 7.92 Inhibition of KEAP1/NRF2 interaction in human BEAS2B cells assessed as induction... 27031670
Keap1/Nrf2 EC50 = 16.0 nM 7.8 Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from CO... 27031670
Keap1/Nrf2 EC50 = 22.0 nM 7.66 Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from CO... 27031670
Keap1/Nrf2 EC50 = 27.0 nM 7.57 Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from CO... 27031670
Keap1/Nrf2 EC50 = 36.0 nM 7.44 Inhibition of KEAP1/NRF2 interaction in human bronchial epithelial cells from CO... 27031670
Kelch-like ECH-associated protein 1 EC50 = 1900.0 nM 5.72 Binding affinity to recombinant human KEAP1 Kelch domain (321 to 609 residues) e... 31411465
Solute carrier organic anion transporter family member 1B1 IC50 = 2500.0 nM 5.6 Inhibition of OATP1B1 (unknown origin) 27031670
Bile salt export pump IC50 = 4000.0 nM 5.4 Inhibition of BSEP (unknown origin) 27031670
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A IC50 = 10000.0 nM 5.0 Inhibition of PDE3A (unknown origin) 27031670

Literature References

PubMed DOI Target Context # Activities
27031670 10.1021/acs.jmedchem.6b00228 Rattus norvegicus 23
27031670 10.1021/acs.jmedchem.6b00228 Keap1/Nrf2 17
31411465 10.1021/acs.jmedchem.9b00723 Kelch-like ECH-associated protein 1 9
27031670 10.1021/acs.jmedchem.6b00228 Blood 3
27031670 10.1021/acs.jmedchem.6b00228 Muscarinic acetylcholine receptor M2 2
27031670 10.1021/acs.jmedchem.6b00228 Kelch-like ECH-associated protein 1 2
27031670 10.1021/acs.jmedchem.6b00228 Unchecked 2
27031670 10.1021/acs.jmedchem.6b00228 Muscarinic acetylcholine receptor M1 2
27031670 10.1021/acs.jmedchem.6b00228 5-hydroxytryptamine receptor 2C 2
27031670 10.1021/acs.jmedchem.6b00228 5-hydroxytryptamine receptor 2A 2
27031670 10.1021/acs.jmedchem.6b00228 5-hydroxytryptamine receptor 3A 2
27031670 10.1021/acs.jmedchem.6b00228 Beta-2 adrenergic receptor 2
27031670 10.1021/acs.jmedchem.6b00228 Kappa-type opioid receptor 2
27031670 10.1021/acs.jmedchem.6b00228 Acetylcholine receptor subunit alpha 2
27031670 10.1021/acs.jmedchem.6b00228 D(2) dopamine receptor 2
27031670 10.1021/acs.jmedchem.6b00228 5-hydroxytryptamine receptor 1B 2
27031670 10.1021/acs.jmedchem.6b00228 Bile salt export pump 1
38621319 10.1016/j.bmc.2024.117718 Kelch-like ECH-associated protein 1 1
27031670 10.1021/acs.jmedchem.6b00228 Alpha-1B adrenergic receptor 1
27031670 10.1021/acs.jmedchem.6b00228 Cannabinoid receptor 2 1

Data from ChEMBL 36 via Core Engine