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Compound Detail

CHEMBL5394686

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COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OCCON1CCN(C)CC1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL5394686
Phase Preclinical
Structure Type MOL
InChI Key OXIJKGCVPJOUEO-UHFFFAOYSA-N
10
Targets
16
Activities
2
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

461.9
MW (Da)
3.73
ALogP
8
HBA
1
HBD
72.0
PSA (Ų)
0.51
QED
0
Ro5 Violations
8
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C22H25ClFN5O3
MW 461.93
Aromatic Rings 3
Heavy Atoms 32
NP-Likeness -1.21

Activity Summary

IC50 15 meas. best 8.6
Kd 1 meas. best 7.68

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Unchecked
CHEMBL612545
 IC50 8.6 8.47 2.5 2
HCC827
CHEMBL4296422
 IC50 8.51 8.51 3.1 1
NCI-H3255
CHEMBL4296476
 IC50 8.14 8.14 7.2 1
Receptor tyrosine-protein kinase erbB-2
CHEMBL1824
 Kd 7.68 7.68 21.0 1
A-431
CHEMBL614069
 IC50 7.08 7.08 83.0 1
AU565
CHEMBL1075393
 IC50 6.01 6.01 986.0 1
Cytochrome P450 2D6
CHEMBL289
 IC50 5.98 5.715 1050.0 6
SK-BR-3
CHEMBL613834
 IC50 5.82 5.82 1510.0 1
ZR-75-30
CHEMBL1075613
 IC50 5.79 5.79 1632.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 5.19 5.19 6480.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 281.78 ng.hr.mL-1 Rattus norvegicus
AUC 1804.76 ng.hr.mL-1 Rattus norvegicus
AUC 400.03 ng.hr.mL-1 Mus musculus
AUC 2445.92 ng.hr.mL-1 Mus musculus
AUC 279.0 ng.hr.mL-1 Rattus norvegicus
CL 46.0 mL.min-1.kg-1 Homo sapiens
CL 146.0 mL.min-1.kg-1 Rattus norvegicus
CL 12.0 mL.min-1.kg-1 Homo sapiens
CL 70.0 mL.min-1.kg-1 Rattus norvegicus
CL 59.6 mL.min-1.kg-1 Rattus norvegicus
CL 58.6 mL.min-1.kg-1 Mus musculus
CL 29.0 mL.min-1.kg-1 Macaca fascicularis
CL 13.0 mL.min-1.kg-1 Canis lupus familiaris
Cmax 653.0 nM Rattus norvegicus
Cmax 2180.0 nM Mus musculus
F 64.0 % Rattus norvegicus
F 61.0 % Mus musculus
Fu 0.044 - Homo sapiens
Fu 0.128 - Rattus norvegicus
Fu 0.07 - Mus musculus
Fu 0.045 - Rattus norvegicus
Fu 0.041 - Mus musculus
T1/2 0.5 hr Homo sapiens
T1/2 0.1583 hr Rattus norvegicus
T1/2 1.948 hr Homo sapiens
T1/2 0.3283 hr Rattus norvegicus
T1/2 2.4 hr Rattus norvegicus
T1/2 2.37 hr Rattus norvegicus
T1/2 1.67 hr Mus musculus
T1/2 1.84 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 2.5 nM 8.6 Antiproliferative activity against mouse Osimertinib-resistant Ba/F3 EGFR-DelE74... 37934858
HCC827 IC50 = 3.1 nM 8.51 Antiproliferative activity against human HCC827 cells harboring EGFR del E746_A7... 37934858
Unchecked IC50 = 4.6 nM 8.34 Antiproliferative activity against mouse Osimertinib-resistant Ba/F3 EGFR-C797S/... 37934858
NCI-H3255 IC50 = 7.2 nM 8.14 Antiproliferative activity against human NCI-H3255 cells harboring EGFR L858R mu... 37934858
Receptor tyrosine-protein kinase erbB-2 Kd = 21.0 nM 7.68 Inhibition of human ERBB2 assessed as dissociation constant by KINOMEScan assay 37934858
A-431 IC50 = 83.0 nM 7.08 Antiproliferative activity against human A-431 cells overexpressing wild type EG... 37934858
AU565 IC50 = 986.0 nM 6.01 Antiproliferative activity against patient-derived HER2-positive human AU565 cel... 37934858
Cytochrome P450 2D6 IC50 = 1050.0 nM 5.98 Time dependent inhibition of CYP2D6 in human liver microsomes assessed as bufura... 37934858
Cytochrome P450 2D6 IC50 = 1100.0 nM 5.96 Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substra... 37934858
Cytochrome P450 2D6 IC50 = 1160.0 nM 5.94 Time dependent inhibition of CYP2D6 in human liver microsomes assessed as bufura... 37934858
SK-BR-3 IC50 = 1510.0 nM 5.82 Antiproliferative activity against patient-derived HER2-positive human SK-BR-3 c... 37934858
ZR-75-30 IC50 = 1632.0 nM 5.79 Antiproliferative activity against patient-derived HER2-positive human ZR-75-30 ... 37934858
Cytochrome P450 2D6 IC50 = 1820.0 nM 5.74 Time dependent inhibition of CYP2D6 in human liver microsomes assessed as bufura... 37934858
Cytochrome P450 2D6 IC50 = 4570.0 nM 5.34 Time dependent inhibition of CYP2D6 in human hepatocytes assessed as dextrometho... 37934858
Cytochrome P450 2D6 IC50 = 4730.0 nM 5.33 Time dependent inhibition of CYP2D6 in human hepatocytes assessed as dextrometho... 37934858
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 6480.0 nM 5.19 Inhibition of human ERG expressed in HEK293 cells by patch clamp assay 37934858

Literature References

PubMed DOI Target Context # Activities
37934858 10.1021/acs.jmedchem.3c01669 ADMET 61
37934858 10.1021/acs.jmedchem.3c01669 Cytochrome P450 2D6 6
37934858 10.1021/acs.jmedchem.3c01669 No relevant target 4
37934858 10.1021/acs.jmedchem.3c01669 Epidermal growth factor receptor 4
37934858 10.1021/acs.jmedchem.3c01669 Voltage-gated inwardly rectifying potassium channel KCNH2 3
37934858 10.1021/acs.jmedchem.3c01669 HCC827 2
37934858 10.1021/acs.jmedchem.3c01669 Unchecked 2
37934858 10.1021/acs.jmedchem.3c01669 Receptor tyrosine-protein kinase erbB-2 2
37934858 10.1021/acs.jmedchem.3c01669 ZR-75-30 1
37934858 10.1021/acs.jmedchem.3c01669 AU565 1
37934858 10.1021/acs.jmedchem.3c01669 1-phosphatidylinositol 3-phosphate 5-kinase 1
37934858 10.1021/acs.jmedchem.3c01669 Tyrosine-protein kinase Lyn 1
37934858 10.1021/acs.jmedchem.3c01669 Serine/threonine-protein kinase 17A 1
37934858 10.1021/acs.jmedchem.3c01669 Tyrosine-protein kinase ABL1 1
37934858 10.1021/acs.jmedchem.3c01669 Cytochrome P450 2C19 1
37934858 10.1021/acs.jmedchem.3c01669 Cytochrome P450 2C9 1
37934858 10.1021/acs.jmedchem.3c01669 Cytochrome P450 1A2 1
37934858 10.1021/acs.jmedchem.3c01669 Cytochrome P450 3A4 1
37934858 10.1021/acs.jmedchem.3c01669 NCI-H1975 1
37934858 10.1021/acs.jmedchem.3c01669 A-431 1

Data from ChEMBL 36 via Core Engine