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Compound Detail

CHEMBL4127396

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CC(=O)Nc1nc(C)c(-c2cc3c(c(NS(C)(=O)=O)c2)C(=O)N([C@@H](C)C2CC2)C3)s1

Basic Information

ChEMBL ID CHEMBL4127396
Phase Preclinical
Structure Type MOL
InChI Key RMZMULPZUXWJGE-NSHDSACASA-N
8
Targets
10
Activities
1
Assay Types
9
PK Parameters
15
Publications
0
Known Names

Molecular Properties

448.6
MW (Da)
3.20
ALogP
6
HBA
2
HBD
108.5
PSA (Ų)
0.71
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C20H24N4O4S2
MW 448.57
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -1.25

Activity Summary

IC50 10 meas. best 9.2

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
IC50 9.2 9.1667 0.6 3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL2189158
IC50 8.6 8.6 2.5 1
PI3-kinase p110-delta/p85-alpha
CHEMBL2111432
IC50 6.6 6.6 251.2 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
IC50 6.1 6.1 794.3 1
PI3-kinase p110-alpha/p85-alpha
CHEMBL2111367
IC50 5.2 5.2 6309.6 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.7 4.7 19952.6 1
PI3K p110 beta/p85 alpha
CHEMBL3038510
IC50 4.7 4.7 19952.6 1
THP-1
CHEMBL614245
IC50 4.7 4.7 19952.6 1

Pharmacokinetic Data

Parameter Value Units Species
CL 0.7 mL.min-1.kg-1 Rattus norvegicus
CL 6.2 mL.min-1.kg-1 Canis lupus familiaris
F 49.0 % Rattus norvegicus
F 1.6 % Canis lupus familiaris
Fu 0.01 - Homo sapiens
Fu 0.01 - Rattus norvegicus
Fu 0.05 - Canis lupus familiaris
T1/2 6.7 hr Rattus norvegicus
T1/2 1.3 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 0.631 nM 9.2 Inhibition of recombinant human 6His-tagged PI3Kgamma (144 to 1102 residues) usi... 29852070
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 0.631 nM 9.2 Enzymatic Activity Assay for Rec Human PI3Kgamma: The activity of recombinant hu... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 0.794 nM 9.1 Enzymatic Activity Assay for Rec Human PI3Kgamma: The activity of recombinant hu... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 2.512 nM 8.6 Inhibition of PI3Kgamma in mouse RAW264 cells assessed as reduction in Akt phosp... 29852070
PI3-kinase p110-delta/p85-alpha IC50 = 251.19 nM 6.6 Inhibition of recombinant human 6His-tagged PI3K p110delta/p85alpha using DiC8-P... 29852070
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform IC50 = 794.33 nM 6.1 Inhibition of PI3Kdelta in human JeKo1B cells assessed as reduction in AKT phosp... 29852070
PI3-kinase p110-alpha/p85-alpha IC50 = 6309.57 nM 5.2 Inhibition of recombinant human 6His-tagged PI3K p110alpha/p85alpha using DiC8-P... 29852070
PI3K p110 beta/p85 alpha IC50 = 19952.62 nM 4.7 Inhibition of recombinant human 6His-tagged PI3K p110beta/p85alpha using DiC8-PI... 29852070
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 19952.62 nM 4.7 Inhibition of human ERG 29852070
THP-1 IC50 = 19952.62 nM 4.7 Cytotoxicity against human THP1 cells 29852070

Literature References

PubMed DOI Target Context # Activities
29852070 10.1021/acs.jmedchem.8b00447 ADMET 4
29852070 10.1021/acs.jmedchem.8b00447 Rattus norvegicus 4
29852070 10.1021/acs.jmedchem.8b00447 Canis familiaris 4
29852070 10.1021/acs.jmedchem.8b00447 No relevant target 3
29852070 10.1021/acs.jmedchem.8b00447 Hepatocyte 3
29852070 10.1021/acs.jmedchem.8b00447 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform 2
29852070 10.1021/acs.jmedchem.8b00447 PI3-kinase p110-alpha/p85-alpha 1
29852070 10.1021/acs.jmedchem.8b00447 PI3K p110 beta/p85 alpha 1
29852070 10.1021/acs.jmedchem.8b00447 PI3-kinase p110-delta/p85-alpha 1
29852070 10.1021/acs.jmedchem.8b00447 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 1
29852070 10.1021/acs.jmedchem.8b00447 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 1
29852070 10.1021/acs.jmedchem.8b00447 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 1
29852070 10.1021/acs.jmedchem.8b00447 Unchecked 1
29852070 10.1021/acs.jmedchem.8b00447 Voltage-gated inwardly rectifying potassium channel KCNH2 1
29852070 10.1021/acs.jmedchem.8b00447 THP-1 1

Data from ChEMBL 36 via Core Engine