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Compound Detail

CHEMBL3408248

AZD-8186
Phase I
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Phase I
C[C@@H](Nc1cc(F)cc(F)c1)c1cc(C(=O)N(C)C)cc2c(=O)cc(N3CCOCC3)oc12

Basic Information

ChEMBL ID CHEMBL3408248
Name AZD-8186
Phase Phase I
Structure Type MOL
InChI Key LMJFJIDLEAWOQJ-CQSZACIVSA-N

Known Names

Azd 8186 Azd-8186 AZD8186
10
Targets
15
Activities
2
Assay Types
12
PK Parameters
20
Publications
3
Known Names
8
Indications
2
Mechanisms

Molecular Properties

457.5
MW (Da)
3.78
ALogP
6
HBA
1
HBD
75.0
PSA (Ų)
0.63
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Extended Properties

Molecular Formula C24H25F2N3O4
MW 457.48
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -1.06

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
PI3-kinase p110-beta subunit inhibitor INHIBITOR Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
PI3-kinase p110-delta subunit inhibitor INHIBITOR Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform

Indications

Breast Neoplasms Breast Neoplasms Carcinoma, Non-Small-Cell Lung Prostatic Neoplasms Prostatic Neoplasms Prostatic Neoplasms, Castration-Resistant Stomach Neoplasms Triple Negative Breast Neoplasms

Activity Summary

IC50 13 meas. best 8.7
Kd 2 meas. best 6.03

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
IC50 8.7 8.54 2.0 3
PI3K p110 beta/p85 alpha
CHEMBL3038510
IC50 8.52 8.52 3.0 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
CHEMBL3130
IC50 7.92 7.845 12.0 2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
CHEMBL4005
IC50 7.46 6.79 35.0 2
PI3-kinase p110-delta/p85-alpha
CHEMBL2111432
IC50 7.44 7.44 36.0 1
PI3-kinase p110-alpha/p85-alpha
CHEMBL2111367
IC50 6.35 6.35 450.0 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
CHEMBL3267
IC50 6.17 5.695 675.0 2
DNA topoisomerase 2-beta
CHEMBL3396
Kd 6.03 6.03 936.0 1
Serine/threonine-protein kinase/endoribonuclease IRE2
CHEMBL4105932
Kd 5.82 5.82 1500.0 1
MDA-MB-231
CHEMBL400
IC50 5.16 5.16 6985.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 548.98 ng.hr.mL-1 Mus musculus
CL 77.0 mL.min-1.kg-1 Mus musculus
CL 73.0 uL/min Mus musculus
CL 36.0 mL.min-1.kg-1 Canis lupus familiaris
CL 11.0 uL/min Canis lupus familiaris
F 18.0 % Mus musculus
F 23.0 % Canis lupus familiaris
Fu 0.16 - Mus musculus
Fu 0.31 - Canis lupus familiaris
Fu 0.19 - Homo sapiens
Vd 1.3 L.kg-1 Mus musculus
Vd 2.2 L.kg-1 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 beta isoform IC50 = 2.0 nM 8.7 In Vitro Enzyme Inhibition Assay: Compounds in 100% DMSO were added to assay pla... -
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform IC50 = 3.0 nM 8.52 Inhibition of PI3Kbeta in PTEN-null human MDA-MB-468 cells assessed as inhibitio... 25514658
PI3K p110 beta/p85 alpha IC50 = 3.0 nM 8.52 Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/huma... 32551006
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform IC50 = 4.0 nM 8.4 Inhibition of human recombinant PI3Kbeta using PIP2 by Kinase-Glo Plus assay 25514658
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform IC50 = 12.0 nM 7.92 Inhibition of human recombinant PI3Kdelta using PIP2 by Kinase-Glo Plus assay 25514658
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform IC50 = 17.0 nM 7.77 Inhibition of PI3Kdelta in human Jeko B cells assessed as inhibition of Akt phos... 25514658
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 35.0 nM 7.46 Inhibition of human recombinant PI3Kalpha using PIP2 by Kinase-Glo Plus assay 25514658
PI3-kinase p110-delta/p85-alpha IC50 = 36.0 nM 7.44 Inhibition of human p110delta catalytic subunit/p85alpha using PIP2 as substrate... 32551006
PI3-kinase p110-alpha/p85-alpha IC50 = 450.0 nM 6.35 Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after... 32551006
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 675.0 nM 6.17 Inhibition of human recombinant PI3Kgamma using PIP2 by Kinase-Glo Plus assay 25514658
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform IC50 = 752.0 nM 6.12 Inhibition of PI3Kalpha mutant human BT474 cells assessed as inhibition of Akt p... 25514658
DNA topoisomerase 2-beta Kd = 936.0 nM 6.03 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Serine/threonine-protein kinase/endoribonuclease IRE2 Kd = 1500.0 nM 5.82 Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ... 29191878
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform IC50 = 6000.0 nM 5.22 Inhibition of human full length p110gamma using PIP2 as substrate after 30 mins ... 32551006
MDA-MB-231 IC50 = 6985.0 nM 5.16 Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition... 34990979

Literature References

PubMed DOI Target Context # Activities
25514658 10.1021/jm501629p Mus musculus 6
25514658 10.1021/jm501629p Canis familiaris 4
29191878 10.1126/science.aan4368 Unchecked 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
32551006 10.1021/acsmedchemlett.0c00095 Unchecked 3
25514658 10.1021/jm501629p Plasma 3
25514658 10.1021/jm501629p Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
25514658 10.1021/jm501629p Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform 2
25514658 10.1021/jm501629p NON-PROTEIN TARGET 2
25514658 10.1021/jm501629p Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
29191878 10.1126/science.aan4368 AP2-associated protein kinase 1 1
29191878 10.1126/science.aan4368 Peroxisomal acyl-coenzyme A oxidase 1 1
29191878 10.1126/science.aan4368 Very long-chain specific acyl-CoA dehydrogenase, mitochondrial 1
34990979 10.1016/j.bmc.2021.116594 MDA-MB-231 1
29191878 10.1126/science.aan4368 Tyrosine-protein kinase ABL2 1
29191878 10.1126/science.aan4368 Tyrosine-protein kinase ABL1 1
25514658 10.1021/jm501629p No relevant target 1
25514658 10.1021/jm501629p Voltage-gated inwardly rectifying potassium channel KCNH2 1

Data from ChEMBL 36 via Core Engine