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Compound Detail

CHEMBL5290005

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CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O

Basic Information

ChEMBL ID CHEMBL5290005
Phase Preclinical
Structure Type MOL
InChI Key LACMSNCHWBQXEK-HXUWFJFHSA-N
7
Targets
14
Activities
2
Assay Types
3
PK Parameters
12
Publications
0
Known Names

Molecular Properties

459.9
MW (Da)
5.30
ALogP
5
HBA
2
HBD
104.7
PSA (Ų)
0.41
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H19ClFN5O
MW 459.91
Aromatic Rings 4
Heavy Atoms 33
NP-Likeness -1.08

Activity Summary

IC50 11 meas. best 7.89
EC50 3 meas. best 5.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
CHEMBL1795194
IC50 7.89 7.03 13.0 4
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
CHEMBL1795194
EC50 5.8 5.4067 1600.0 3
Cytochrome P450 2C8
CHEMBL3721
IC50 5.64 5.64 2300.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.47 5.47 3400.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.08 5.04 8350.0 2
EBC-1
CHEMBL4296411
IC50 5.02 5.02 9500.0 1
NCI-H460
CHEMBL396
IC50 4.67 4.67 21200.0 1
THP-1
CHEMBL614245
IC50 4.52 4.52 30000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 2.333 mL.min-1.kg-1 Rattus norvegicus
CL 5.0 mL.min-1.kg-1 Rattus norvegicus
CL - mL.min-1.kg-1 Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha IC50 = 13.0 nM 7.89 Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expres... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha IC50 = 69.0 nM 7.16 Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expres... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha IC50 = 110.0 nM 6.96 Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expres... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha IC50 = 770.0 nM 6.11 Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expres... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha EC50 = 1600.0 nM 5.8 Binding affinity to human PIP4K2A in human THP-1 intact cells sessed as thermal ... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha EC50 = 2100.0 nM 5.68 Binding affinity to human PIP4K2A in human THP-1 cell lysate assessed as thermal... 34699202
Cytochrome P450 2C8 IC50 = 2300.0 nM 5.64 Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by... 34699202
Cytochrome P450 2C9 IC50 = 3400.0 nM 5.47 Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate by ... 34699202
Cytochrome P450 3A4 IC50 = 8350.0 nM 5.08 Inhibition of CYP3A4 in human liver microsomes preincubated with compound follow... 34699202
EBC-1 IC50 = 9500.0 nM 5.02 Antiproliferative activity against human EBC-1 cells harboring p53 mutation asse... 34699202
Cytochrome P450 3A4 IC50 = 10000.0 nM 5.0 Inhibition of CYP3A4 in human liver microsomes using dextromethorphan as substra... 34699202
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha EC50 = 18100.0 nM 4.74 Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in mitocho... 34699202
NCI-H460 IC50 = 21200.0 nM 4.67 Antiproliferative activity against human NCI-H460 cells harboring wild type p53 ... 34699202
THP-1 IC50 = 30000.0 nM 4.52 Antiproliferative activity against human THP-1 cells harboring p53 mutation asse... 34699202

Literature References

PubMed DOI Target Context # Activities
34699202 10.1021/acs.jmedchem.1c01245 Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha 12
34699202 10.1021/acs.jmedchem.1c01245 ADMET 11
34699202 10.1021/acs.jmedchem.1c01245 No relevant target 5
34699202 10.1021/acs.jmedchem.1c01245 Cytochrome P450 3A4 2
34699202 10.1021/acs.jmedchem.1c01245 Voltage-gated inwardly rectifying potassium channel KCNH2 1
34699202 10.1021/acs.jmedchem.1c01245 Cytochrome P450 1A2 1
34699202 10.1021/acs.jmedchem.1c01245 Cytochrome P450 2C8 1
34699202 10.1021/acs.jmedchem.1c01245 Cytochrome P450 2C9 1
34699202 10.1021/acs.jmedchem.1c01245 Cytochrome P450 2D6 1
34699202 10.1021/acs.jmedchem.1c01245 THP-1 1
34699202 10.1021/acs.jmedchem.1c01245 EBC-1 1
34699202 10.1021/acs.jmedchem.1c01245 NCI-H460 1

Data from ChEMBL 36 via Core Engine