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Compound Detail

CHEMBL1738758

ONVANSERTIB
🧪 Phase II
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🧪 Phase II
CN1CCN(c2ccc(OC(F)(F)F)c(Nc3ncc4c(n3)-c3c(c(C(N)=O)nn3CCO)CC4)c2)CC1

Basic Information

ChEMBL ID CHEMBL1738758
Name ONVANSERTIB
Phase Phase II
Structure Type MOL
InChI Key QHLVBNKYJGBCQJ-UHFFFAOYSA-N

Known Names

Nms-1286937 NMS-P937 Onvansertib PCM-075
167
Targets
199
Activities
2
Assay Types
30
PK Parameters
20
Publications
4
Known Names
6
Indications
1
Mechanisms

Molecular Properties

532.5
MW (Da)
1.92
ALogP
10
HBA
3
HBD
134.7
PSA (Ų)
0.42
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -sertib
USAN Year 2018

Extended Properties

Molecular Formula C24H27F3N8O3
MW 532.53
Aromatic Rings 3
Heavy Atoms 38
NP-Likeness -1.38

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serine/threonine-protein kinase PLK1 inhibitor INHIBITOR Serine/threonine-protein kinase PLK1

Indications

Carcinoma, Pancreatic Ductal Prostatic Neoplasms, Castration-Resistant Inflammatory Breast Neoplasms Leukemia, Myeloid, Acute Neoplasms Pancreatic Neoplasms

Activity Summary

IC50 198 meas. best 8.7
Ki 1 meas. best 8.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serine/threonine-protein kinase PLK1
CHEMBL3024
Ki 8.8 8.8 1.6 1
Serine/threonine-protein kinase PLK1
CHEMBL3024
IC50 8.7 8.45 2.0 6
MFM-223
CHEMBL1075504
IC50 8.0 8.0 10.0 1
AU565
CHEMBL1075393
IC50 7.96 7.96 11.0 1
HCC1954
CHEMBL1075459
IC50 7.82 7.82 15.0 1
NCI-H2170
CHEMBL1075534
IC50 7.82 7.82 15.0 1
Unchecked
CHEMBL612545
IC50 7.82 6.8414 15.0 22
NCI-H82
CHEMBL2366077
IC50 7.8 7.8 16.0 1
HCC1806
CHEMBL1075457
IC50 7.75 7.75 18.0 1
CAL-51
CHEMBL1075411
IC50 7.72 7.72 19.0 1
KU812 cell line
CHEMBL613997
IC50 7.7 7.7 20.0 1
MOLM-13
CHEMBL3706572
IC50 7.66 7.66 22.0 1
MDA-MB-435S
CHEMBL4483284
IC50 7.64 7.64 23.0 1
697
CHEMBL2366253
IC50 7.58 7.58 26.0 1
Granta-519
CHEMBL4483240
IC50 7.54 7.54 29.0 1
SH-SY5Y
CHEMBL614910
IC50 7.52 7.52 30.0 1
NCI-H526
CHEMBL2366102
IC50 7.51 7.51 31.0 1
SU-DHL-8
CHEMBL4523562
IC50 7.51 7.51 31.0 1
LCLC-97TM1
CHEMBL1075489
IC50 7.5 7.5 32.0 1
SW48
CHEMBL614055
IC50 7.5 7.5 32.0 1
THP-1
CHEMBL614245
IC50 7.5 7.5 32.0 1
COLO 205
CHEMBL614561
IC50 7.5 7.5 32.0 1
NCI-H522
CHEMBL614387
IC50 7.47 7.47 34.0 1
SK-BR-3
CHEMBL613834
IC50 7.46 7.46 35.0 1
L-363
CHEMBL2366267
IC50 7.43 7.43 37.0 1
SW-620
CHEMBL612262
IC50 7.43 7.43 37.0 1
OPM-2
CHEMBL2366353
IC50 7.42 7.42 38.0 1
NCI-H1437
CHEMBL1075513
IC50 7.41 7.41 39.0 1
HT-29
CHEMBL384
IC50 7.41 7.41 39.0 1
U-266
CHEMBL2366315
IC50 7.4 7.4 40.0 1
A-375
CHEMBL613859
IC50 7.4 7.4 40.0 1
A2780
CHEMBL614004
IC50 7.4 7.39 40.0 2
U-937
CHEMBL612794
IC50 7.39 7.39 41.0 1
OVCAR-3
CHEMBL614213
IC50 7.39 7.39 41.0 1
EVSA-T
CHEMBL614295
IC50 7.39 7.39 41.0 1
HCC1419
CHEMBL1075455
IC50 7.38 7.38 42.0 1
Toledo
CHEMBL4296505
IC50 7.38 7.38 42.0 1
RS4-11
CHEMBL2366159
IC50 7.37 7.37 43.0 1
SU-DHL10
CHEMBL4483268
IC50 7.37 7.37 43.0 1
MOLT-4
CHEMBL614177
IC50 7.35 7.35 45.0 1
SAOS-2
CHEMBL614894
IC50 7.35 7.35 45.0 1
KMS-11
CHEMBL4296454
IC50 7.34 7.34 46.0 1
SW-403
CHEMBL6066749
IC50 7.34 7.34 46.0 1
DU-4475
CHEMBL2366246
IC50 7.33 7.33 47.0 1
SR
CHEMBL614300
IC50 7.33 7.33 47.0 1
SF-539
CHEMBL614860
IC50 7.33 7.33 47.0 1
Jurkat
CHEMBL397
IC50 7.32 7.32 48.0 1
HEL
CHEMBL613888
IC50 7.32 7.32 48.0 1
HCC1395
CHEMBL1075454
IC50 7.31 7.31 49.0 1
BT-549
CHEMBL614072
IC50 7.31 7.31 49.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 4579.76 ng.hr.mL-1 Mus musculus
AUC 7348.91 ng.hr.mL-1 Rattus norvegicus
AUC 2236.63 ng.hr.mL-1 Canis lupus familiaris
AUC 7508.67 ng.hr.mL-1 Macaca fascicularis
AUC 1065.06 ng.hr.mL-1 Mus musculus
AUC 24709.39 ng.hr.mL-1 Rattus norvegicus
AUC 4313.49 ng.hr.mL-1 Canis lupus familiaris
AUC 7881.44 ng.hr.mL-1 Macaca fascicularis
CL 165.0 mL.min-1.kg-1 Rattus norvegicus
CL 16.9 mL.min-1.kg-1 Homo sapiens
CL 39.4 mL.min-1.kg-1 Mus musculus
CL 20.6 mL.min-1.kg-1 Rattus norvegicus
CL 43.8 mL.min-1.kg-1 Canis lupus familiaris
CL 11.2 mL.min-1.kg-1 Macaca fascicularis
Cmax 8300.0 nM Mus musculus
Cmax 6800.0 nM Rattus norvegicus
Cmax 1700.0 nM Canis lupus familiaris
Cmax 3000.0 nM Macaca fascicularis
Cmax 600.0 nM Mus musculus
Cmax 4200.0 nM Rattus norvegicus
Cmax 1200.0 nM Canis lupus familiaris
Cmax 1900.0 nM Macaca fascicularis
F 24.0 % Mus musculus
F 100.0 % Rattus norvegicus
F 63.0 % Canis lupus familiaris
F 35.0 % Macaca fascicularis
T1/2 0.9 hr Mus musculus
T1/2 2.7 hr Rattus norvegicus
T1/2 3.9 hr Canis lupus familiaris
T1/2 5.0 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serine/threonine-protein kinase PLK1 Ki = 1.58 nM 8.8 Binding affinity to PLK1 (unknown origin) assessed as inhibition constant incuba... 22319201
Serine/threonine-protein kinase PLK1 IC50 = 2.0 nM 8.7 Affinity Biochemical interaction (Radiometric kinase assay) EUB0000677a PLK1 -
Serine/threonine-protein kinase PLK1 IC50 = 2.0 nM 8.7 Inhibition of PLK1 (unknown origin) in presence of [gamma-33P]ATP 22319201
Serine/threonine-protein kinase PLK1 IC50 = 2.0 nM 8.7 Inhibition of PLK1 (unknown origin) by ATP competitive assay 36889251
Serine/threonine-protein kinase PLK1 IC50 = 2.0 nM 8.7 Inhibition of PLK1 assessed as [33P]gamma-ATP incorporation into substrate after... 21470862
Serine/threonine-protein kinase PLK1 IC50 = 3.0 nM 8.52 Biochemical Assay: The inhibitory activity of putative kinase inhibitors and the... -
MFM-223 IC50 = 10.0 nM 8.0 Antiproliferative activity against human MFM-223 cells assessed as inhibition of... 22319201
AU565 IC50 = 11.0 nM 7.96 Antiproliferative activity against human AU565 cells assessed as inhibition of c... 22319201
HCC1954 IC50 = 15.0 nM 7.82 Antiproliferative activity against human HCC1954 cells assessed as inhibition of... 22319201
Unchecked IC50 = 15.0 nM 7.82 Antiproliferative activity against human HCC15 cells assessed as inhibition of c... 22319201
NCI-H2170 IC50 = 15.0 nM 7.82 Antiproliferative activity against human NCI-H2170 cells assessed as inhibition ... 22319201
NCI-H82 IC50 = 16.0 nM 7.8 Antiproliferative activity against human NCI-H82 cells assessed as inhibition of... 22319201
HCC1806 IC50 = 18.0 nM 7.75 Antiproliferative activity against human HCC1806 cells assessed as inhibition of... 22319201
CAL-51 IC50 = 19.0 nM 7.72 Antiproliferative activity against human CAL-51 cells assessed as inhibition of ... 22319201
KU812 cell line IC50 = 20.0 nM 7.7 Antiproliferative activity against human KU812 cell line assessed as inhibition ... 22319201
MOLM-13 IC50 = 22.0 nM 7.66 Antiproliferative activity against human MOLM-13 cells assessed as inhibition of... 22319201
Unchecked IC50 = 22.0 nM 7.66 Antiproliferative activity against human PL-21 cells assessed as inhibition of c... 22319201
MDA-MB-435S IC50 = 23.0 nM 7.64 Antiproliferative activity against human MDA-MB-435S cells assessed as inhibitio... 22319201
697 IC50 = 26.0 nM 7.58 Antiproliferative activity against human 697 cells assessed as inhibition of cel... 22319201
Granta-519 IC50 = 29.0 nM 7.54 Antiproliferative activity against human Granta-519 cells assessed as inhibition... 22319201

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 HEK-293T 346
- 10.6019/CHEMBL4689842 U2OS 345
- 10.6019/CHEMBL4689842 Fibroblast 344
22319201 10.1158/1535-7163.mct-11-0765 Unchecked 44
22319201 10.1158/1535-7163.mct-11-0765 ADMET 43
22319201 10.1158/1535-7163.mct-11-0765 A2780 17
22319201 10.1158/1535-7163.mct-11-0765 Tyrosine-protein kinase ABL1 15
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
22319201 10.1158/1535-7163.mct-11-0765 Mast/stem cell growth factor receptor Kit 11
22319201 10.1158/1535-7163.mct-11-0765 Epidermal growth factor receptor 9
22319201 10.1158/1535-7163.mct-11-0765 Serine/threonine-protein kinase PLK1 8
22319201 10.1158/1535-7163.mct-11-0765 Proto-oncogene tyrosine-protein kinase receptor Ret 7
22319201 10.1158/1535-7163.mct-11-0765 U2OS 7
22319201 10.1158/1535-7163.mct-11-0765 HL-60 7
22319201 10.1158/1535-7163.mct-11-0765 MAP kinase-activated protein kinase 2 7
22319201 10.1158/1535-7163.mct-11-0765 Serine/threonine-protein kinase Chk2 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
22319201 10.1158/1535-7163.mct-11-0765 Receptor-type tyrosine-protein kinase FLT3 6
22319201 10.1158/1535-7163.mct-11-0765 Proto-oncogene tyrosine-protein kinase Src 6

Data from ChEMBL 36 via Core Engine