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Compound Detail

CHEMBL4647810

ELIMUSERTIB
Phase I
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Phase I
C[C@@H]1COCCN1c1cc(-c2ccnn2C)c2ccnc(-c3ccn[nH]3)c2n1

Basic Information

ChEMBL ID CHEMBL4647810
Name ELIMUSERTIB
Phase Phase I
Structure Type MOL
InChI Key YBXRSCXGRPSTMW-CYBMUJFWSA-N

Known Names

BAY-1895344 Elimusertib
16
Targets
29
Activities
3
Assay Types
13
PK Parameters
20
Publications
2
Known Names
4
Indications
1
Mechanisms

Molecular Properties

375.4
MW (Da)
2.65
ALogP
7
HBA
1
HBD
84.8
PSA (Ų)
0.59
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer
USAN Stem -sertib

Extended Properties

Molecular Formula C20H21N7O
MW 375.44
Aromatic Rings 4
Heavy Atoms 28
NP-Likeness -1.36

Mechanism of Action

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

Indications

Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Neoplasms Ovarian Neoplasms

Activity Summary

IC50 24 meas. best 9.22
Kd 3 meas. best 7.62
Ki 2 meas. best 8.42

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase ATR
CHEMBL5024
IC50 9.22 8.3 0.6 6
Serine/threonine-protein kinase ATR
CHEMBL5024
Ki 8.42 8.285 3.8 2
ATR/ATRIP
CHEMBL4106138
IC50 8.15 7.7275 7.0 4
SU-DHL-8
CHEMBL4523562
IC50 8.05 8.05 9.0 2
Serine/threonine-protein kinase mTOR
CHEMBL2842
Kd 7.62 7.62 24.0 1
LoVo
CHEMBL614721
IC50 7.57 7.37 27.0 3
Molecular identity unknown
CHEMBL612546
IC50 7.46 7.46 35.0 1
A549
CHEMBL392
IC50 7.05 7.05 90.0 1
HT-29
CHEMBL384
IC50 6.8 6.8 160.0 1
DNA-dependent protein kinase catalytic subunit
CHEMBL3142
IC50 6.48 6.48 332.0 1
Cyclin-G-associated kinase
CHEMBL4355
Kd 6.24 6.24 580.0 1
Serine/threonine-protein kinase RIO2
CHEMBL6000
Kd 6.18 6.18 660.0 1
Serine-protein kinase ATM
CHEMBL3797
IC50 5.85 5.85 1420.0 1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
CHEMBL3145
IC50 5.49 5.49 3270.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.16 5.16 7000.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.01 5.01 9800.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.96 4.96 11000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 6.833 mL.min-1.kg-1 Homo sapiens
CL 12.33 mL.min-1.kg-1 Rattus norvegicus
CL 8.667 mL.min-1.kg-1 Rattus norvegicus
CL 20.0 mL.min-1.kg-1 Rattus norvegicus
CL 13.17 mL.min-1.kg-1 Canis lupus familiaris
CL 58.33 mL.min-1.kg-1 Mus musculus
F 87.0 % Rattus norvegicus
F 51.0 % Canis lupus familiaris
Fu 0.03 - Homo sapiens
Fu 0.17 - Rattus norvegicus
T1/2 1.3 hr Rattus norvegicus
T1/2 0.17 hr Mus musculus
T1/2 1.0 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase ATR IC50 = 0.6 nM 9.22 Inhibition of ATR in gemcitabine-stimulated human LoVo cells assessed as decreas... 38299539
Serine/threonine-protein kinase ATR IC50 = 2.0 nM 8.7 Inhibition of ATR in human HeLa S3 cells assessed as decrease in CHK1 phosphoryl... 38299539
Serine/threonine-protein kinase ATR Ki = 3.8 nM 8.42 Inhibition of ATR (unknown origin) by Morrison equation based analysis 38299539
Serine/threonine-protein kinase ATR Ki = 7.0 nM 8.15 Binding affinity to ATR (unknown origin) assessed as inhibition constant 35793579
Serine/threonine-protein kinase ATR IC50 = 7.0 nM 8.15 Inhibition of ATR (unknown origin) 38325007
Serine/threonine-protein kinase ATR IC50 = 7.0 nM 8.15 Inhibition of 5'-TAMRA-labeled tracer 3',6'-bis(dimethylamino)-N-(4-{[2(1H-indol... 32502336
ATR/ATRIP IC50 = 7.0 nM 8.15 Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full ... 33135887
Serine/threonine-protein kinase ATR IC50 = 7.24 nM 8.14 Time-Resolved Fluorescence Energy Transfer (TR-FRET Tracer A): To determine of b... -
ATR/ATRIP IC50 = 7.24 nM 8.14 Binding Assay ATR (tracer A): To determine of binding activity of the test compo... -
ATR/ATRIP IC50 = 7.24 nM 8.14 Binding Assay ATR (tracer A): For the assay 50 nl of a 100-fold concentrated sol... -
SU-DHL-8 IC50 = 9.0 nM 8.05 Antiproliferative activity against human SU-DHL-8 cells measured after 72 to 96 ... 33135887
SU-DHL-8 IC50 = 9.0 nM 8.05 Antiproliferative activity against human SUDHL8 cells assessed as reduction in c... 32502336
Serine/threonine-protein kinase mTOR Kd = 24.0 nM 7.62 Binding affinity to wild-type human partial length mTOR (L1382 to W2549 residues... 32502336
LoVo IC50 = 27.0 nM 7.57 Cytotoxicity against human LoVo cells assessed as reduction in cell viability in... 38299539
Molecular identity unknown IC50 = 35.0 nM 7.46 Inhibition of PI3K/AKT/mTOR signaling pathway in human MCF7 cells assessed as re... 32502336
Serine/threonine-protein kinase ATR IC50 = 36.0 nM 7.44 Inhibition of ATR in human HT-29 cells assessed as reduction in histone H2AX pho... 32502336
LoVo IC50 = 41.0 nM 7.39 Antiproliferative activity against human LoVo cells incubated for 72 hrs by CCK-... 37130473
LoVo IC50 = 71.0 nM 7.15 Antiproliferative activity against human LoVo cells assessed as reduction in cel... 32502336
A549 IC50 = 90.0 nM 7.05 Cytotoxicity against human A549 cells assessed as reduction in cell viability me... 35191694
HT-29 IC50 = 160.0 nM 6.8 Antiproliferative activity against human HT-29 cells assessed as reduction in ce... 32502336

Literature References

PubMed DOI Target Context # Activities
32502336 10.1021/acs.jmedchem.0c00369 ADMET 23
38299539 10.1021/acs.jmedchem.3c01917 Unchecked 5
32502336 10.1021/acs.jmedchem.0c00369 Serine/threonine-protein kinase ATR 4
32502336 10.1021/acs.jmedchem.0c00369 Cytochrome P450 3A4 4
32502336 10.1021/acs.jmedchem.0c00369 Unchecked 3
38325007 10.1016/j.ejmech.2024.116159 Unchecked 3
38299539 10.1021/acs.jmedchem.3c01917 Serine/threonine-protein kinase ATR 3
38299539 10.1021/acs.jmedchem.3c01917 ADMET 3
37130473 10.1016/j.ejmech.2023.115370 LoVo 2
32502336 10.1021/acs.jmedchem.0c00369 No relevant target 2
32502336 10.1021/acs.jmedchem.0c00369 SU-DHL-8 2
32502336 10.1021/acs.jmedchem.0c00369 Molecular identity unknown 1
32502336 10.1021/acs.jmedchem.0c00369 Serine-protein kinase ATM 1
32502336 10.1021/acs.jmedchem.0c00369 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform 1
32502336 10.1021/acs.jmedchem.0c00369 Serine/threonine-protein kinase mTOR 1
32502336 10.1021/acs.jmedchem.0c00369 Cyclin-G-associated kinase 1
32502336 10.1021/acs.jmedchem.0c00369 Serine/threonine-protein kinase RIO2 1
32502336 10.1021/acs.jmedchem.0c00369 Cytochrome P450 1A2 1
32502336 10.1021/acs.jmedchem.0c00369 Voltage-gated inwardly rectifying potassium channel KCNH2 1
32502336 10.1021/acs.jmedchem.0c00369 Cytochrome P450 2C8 1

Data from ChEMBL 36 via Core Engine