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Compound Detail

CHEMBL4285417

CERALASERTIB
🧪 Phase III
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🧪 Phase III
C[C@@H]1COCCN1c1cc(C2([S@](C)(=N)=O)CC2)nc(-c2cc[nH]c3nccc2-3)n1

Basic Information

ChEMBL ID CHEMBL4285417
Name CERALASERTIB
Phase Phase III
Structure Type MOL
InChI Key OHUHVTCQTUDPIJ-JYCIKRDWSA-N

Known Names

Atr kinase inhibitor azd6738 Azd 6738 Azd-6738 AZD6738 Ceralasertib
18
Targets
35
Activities
3
Assay Types
13
PK Parameters
20
Publications
5
Known Names
20
Indications
1
Mechanisms

Molecular Properties

412.5
MW (Da)
2.86
ALogP
7
HBA
2
HBD
107.8
PSA (Ų)
0.68
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -sertib
USAN Year 2019

Extended Properties

Molecular Formula C20H24N6O2S
MW 412.52
Aromatic Rings 1
Heavy Atoms 29
NP-Likeness -0.71

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine-protein kinase ATR inhibitor INHIBITOR Serine/threonine-protein kinase ATR

Indications

Carcinoma, Non-Small-Cell Lung Adenocarcinoma Bile Duct Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Carcinoma Carcinoma, Squamous Cell Carcinoma, Squamous Cell Cholangiocarcinoma Melanoma Neoplasms Neoplasms Osteosarcoma Ovarian Neoplasms Prostatic Neoplasms, Castration-Resistant Small Cell Lung Carcinoma Triple Negative Breast Neoplasms Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Prolymphocytic

Activity Summary

IC50 30 meas. best 9.0
Kd 4 meas. best 6.76
Ki 1 meas. best 10.22

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase ATR
CHEMBL5024
Ki 10.22 10.22 0.1 1
Serine/threonine-protein kinase ATR
CHEMBL5024
IC50 9.0 7.7525 1.0 8
ATR/ATRIP
CHEMBL4106138
IC50 7.85 7.85 14.0 1
Unchecked
CHEMBL612545
IC50 6.87 6.87 134.0 1
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
Kd 6.76 6.17 175.0 4
Serine/threonine-protein kinase mTOR
CHEMBL2842
IC50 6.43 5.6967 370.0 3
LoVo
CHEMBL614721
IC50 6.42 6.1467 377.0 3
OCI-Ly10
CHEMBL4483285
IC50 6.28 6.28 520.0 1
Granta-519
CHEMBL4483240
IC50 6.26 6.26 550.0 1
A2780
CHEMBL614004
IC50 6.21 6.21 620.0 1
HCT-116
CHEMBL394
IC50 5.95 5.695 1120.0 2
NCI-H446
CHEMBL612440
IC50 5.71 5.71 1960.0 1
A549
CHEMBL392
IC50 5.7 5.7 2000.0 1
SUD4
CHEMBL613711
IC50 5.65 5.65 2260.0 1
HT-29
CHEMBL384
IC50 5.59 5.59 2590.0 1
DLD-1
CHEMBL614285
IC50 5.28 5.28 5280.0 1
CAPAN-1
CHEMBL614536
IC50 5.26 5.26 5540.0 1
DNA-dependent protein kinase catalytic subunit
CHEMBL3142
IC50 5.13 5.13 7400.0 1
PC-3
CHEMBL390
IC50 4.95 4.95 11280.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 37350.0 ng.hr.mL-1 Mus musculus
AUC 41583.0 ng.hr.mL-1 Mus musculus
CL 22.0 % Rattus norvegicus
CL 10.0 % Canis lupus familiaris
Cmax 12.0 ug.mL-1 Mus musculus
F 67.0 % Rattus norvegicus
F 100.0 % Canis lupus familiaris
Fu 0.26 - Homo sapiens
Fu 0.54 - Mus musculus
T1/2 11.0 hr Homo sapiens
T1/2 1.93 hr Mus musculus
Tmax 1.5 hr Homo sapiens
Tmax 0.25 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase ATR Ki = 0.06 nM 10.22 Inhibition of ATR (unknown origin) by Morrison equation based analysis 38299539
Serine/threonine-protein kinase ATR IC50 = 1.0 nM 9.0 Inhibition of ATR (unknown origin) 38325007
Serine/threonine-protein kinase ATR IC50 = 3.747 nM 8.43 Enzyme Assay: ATR for use in the in vitro enzyme assay was obtained from HeLa nu... -
Serine/threonine-protein kinase ATR IC50 = 4.0 nM 8.4 Inhibition of ATR in human HeLa cell nuclear extract using GST-fused p53N66 as s... 30346772
ATR/ATRIP IC50 = 14.0 nM 7.85 Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3... 38299539
Serine/threonine-protein kinase ATR IC50 = 18.0 nM 7.75 Inhibition of human recombinant full length ATR using GST-cMyc-p53 as substrate ... 35183872
Serine/threonine-protein kinase ATR IC50 = 47.0 nM 7.33 Inhibition of ATR in gemcitabine-stimulated human LoVo cells assessed as decreas... 38299539
Serine/threonine-protein kinase ATR IC50 = 58.34 nM 7.23 Cellular Assay: ATM and ATR have distinct and overlapping responses to DNA damag... -
Serine/threonine-protein kinase ATR IC50 = 74.0 nM 7.13 Inhibition of ATR in human HT29 cells after 60 mins by Hoechst 33258 staining-ba... 30346772
Unchecked IC50 = 134.0 nM 6.87 Inhibition of human full length recombinant ATR M211T mutant using GST-c-Myc-p53... 38299539
Transcription initiation factor TFIID subunit 1 Kd = 175.0 nM 6.76 Binding affinity to human TAF1 BD 2 (1501 to 1635 residues) transfected in Esche... 35191694
Serine/threonine-protein kinase ATR IC50 = 180.0 nM 6.75 Inhibition of ATR in human HeLa S3 cells assessed as decrease in CHK1 phosphoryl... 38299539
Serine/threonine-protein kinase mTOR IC50 = 370.0 nM 6.43 Inhibition of mTOR (unknown origin) 30346772
LoVo IC50 = 377.0 nM 6.42 Cytotoxicity against human LoVo cells assessed as reduction in cell viability in... 38299539
Transcription initiation factor TFIID subunit 1 Kd = 427.0 nM 6.37 Binding affinity to human TAF1 BD 2 (1501 to 1635 residues) transfected in Esche... 35191694
OCI-Ly10 IC50 = 520.0 nM 6.28 Antiproliferative activity against human OCI-Ly10 cells assessed as inhibition o... 39053006
Granta-519 IC50 = 550.0 nM 6.26 Antiproliferative activity against human Granta-519 cells assessed as inhibition... 39053006
A2780 IC50 = 620.0 nM 6.21 Antiproliferative activity against human A2780 cells assessed as inhibition of c... 39053006
LoVo IC50 = 830.0 nM 6.08 Antiproliferative activity against ATM deficient human LoVo cells incubated for ... 38325007
HCT-116 IC50 = 1120.0 nM 5.95 Antiproliferative activity against human HCT-116 cells assessed as inhibition of... 39053006

Literature References

Data from ChEMBL 36 via Core Engine