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Compound Detail

CHEMBL220241

GSK-269962A
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CCn1c(-c2nonc2N)nc2cnc(Oc3cccc(NC(=O)c4ccc(OCCN5CCOCC5)cc4)c3)cc21

Basic Information

ChEMBL ID CHEMBL220241
Name GSK-269962A
Phase Preclinical
Structure Type MOL
InChI Key YOVNFNXUCOWYSG-UHFFFAOYSA-N
283
Targets
422
Activities
2
Assay Types
5
PK Parameters
20
Publications
0
Known Names

Molecular Properties

570.6
MW (Da)
3.84
ALogP
12
HBA
2
HBD
155.7
PSA (Ų)
0.25
QED
2
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C29H30N8O5
MW 570.61
Aromatic Rings 5
Heavy Atoms 42
NP-Likeness -1.80

Activity Summary

IC50 378 meas. best 9.86
Ki 44 meas. best 8.5

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
SR
CHEMBL614300
IC50 9.86 9.86 0.1 1
Rho-associated protein kinase 1
CHEMBL3231
IC50 8.8 8.02 1.6 6
Ribosomal protein S6 kinase beta-1
CHEMBL4501
Ki 8.5 8.5 3.2 1
Rho-associated protein kinase 2
CHEMBL2973
IC50 8.4 8.0033 4.0 3
KS-1
CHEMBL2366228
IC50 8.34 8.34 4.6 1
Protein kinase C delta type
CHEMBL2996
Ki 8.3 8.3 5.0 1
GI-1
CHEMBL2366272
IC50 8.28 8.28 5.2 1
BB49-HNC
CHEMBL2366295
IC50 8.1 8.1 7.9 1
Serine/threonine-protein kinase N2
CHEMBL3032
Ki 7.6 7.6 25.1 1
Protein kinase C zeta type
CHEMBL3438
Ki 7.6 7.6 25.1 1
Protein kinase C iota type
CHEMBL2598
Ki 7.5 7.5 31.6 1
cAMP-dependent protein kinase catalytic subunit alpha
CHEMBL4101
Ki 7.5 7.5 31.6 1
Aorta
CHEMBL613606
IC50 7.46 7.46 35.0 2
Ribosomal protein S6 kinase alpha-3
CHEMBL2345
Ki 7.4 7.4 39.8 1
cGMP-dependent protein kinase 2
CHEMBL2896
Ki 7.4 7.4 39.8 1
Ribosomal protein S6 kinase alpha-5
CHEMBL4237
IC50 7.31 7.31 49.0 1
GI-ME-N
CHEMBL2366074
IC50 7.3 7.3 49.5 1
Glycogen synthase kinase-3 alpha
CHEMBL2850
Ki 7.3 7.3 50.1 1
cAMP-dependent protein kinase catalytic subunit PRKX
CHEMBL5818
Ki 7.3 7.3 50.1 1
Testis-specific serine/threonine-protein kinase 1
CHEMBL6003
Ki 7.3 7.3 50.1 1
Glycogen synthase kinase-3 beta
CHEMBL262
Ki 7.2 7.2 63.1 1
Ribosomal protein S6 kinase alpha-5
CHEMBL4237
Ki 7.2 7.2 63.1 1
MHH-NB-11
CHEMBL2366185
IC50 7.17 7.17 66.9 1
Cell division cycle 7-related protein kinase
CHEMBL5443
Ki 7.1 7.1 79.4 1
D-263MG
CHEMBL2366183
IC50 7.07 7.07 85.1 1
Ribosomal protein S6 kinase alpha-1
CHEMBL2553
IC50 6.88 6.88 132.0 1
NB10
CHEMBL2366243
IC50 6.86 6.86 137.8 1
MV4-11
CHEMBL613835
IC50 6.86 6.86 139.2 1
BE-13
CHEMBL2366303
IC50 6.85 6.85 140.8 1
cGMP-dependent protein kinase 1
CHEMBL4273
Ki 6.8 6.8 158.5 1
Serine/threonine-protein kinase MRCK alpha
CHEMBL4516
Ki 6.8 6.8 158.5 1
Serine/threonine-protein kinase 17A
CHEMBL4525
Ki 6.8 6.8 158.5 1
Serine/threonine-protein kinase Sgk2
CHEMBL5794
Ki 6.7 6.7 199.5 1
ES6
CHEMBL2366373
IC50 6.61 6.61 247.3 1
Protein kinase C gamma type
CHEMBL2938
Ki 6.6 6.6 251.2 1
697
CHEMBL2366253
IC50 6.52 6.52 299.1 1
Serine/threonine-protein kinase pim-1
CHEMBL2147
Ki 6.5 6.5 316.2 1
Serine/threonine-protein kinase PLK4
CHEMBL3788
Ki 6.5 6.5 316.2 1
RXF 393
CHEMBL614886
IC50 6.41 6.41 393.0 1
QIMR-WIL
CHEMBL2366337
IC50 6.31 6.31 490.0 1
Death-associated protein kinase 3
CHEMBL2468
Ki 6.3 6.3 501.2 1
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
Ki 6.3 6.3 501.2 1
Aurora kinase A
CHEMBL4722
Ki 6.3 6.3 501.2 1
KGN
CHEMBL2366154
IC50 6.25 6.25 567.4 1
MRK-nu-1
CHEMBL2366325
IC50 6.24 6.24 575.7 1
NB6
CHEMBL2366318
IC50 6.23 6.23 591.1 1
D-336MG
CHEMBL2366113
IC50 6.2 6.2 628.5 1
D-247MG
CHEMBL2366237
IC50 6.2 6.2 628.1 1
RAC-beta serine/threonine-protein kinase
CHEMBL2431
Ki 6.2 6.2 631.0 1
Dual specificity protein kinase CLK4
CHEMBL4203
Ki 6.2 6.2 631.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 7.6 mL.min-1.kg-1 Rattus norvegicus
Cmax 2225.69 nM Rattus norvegicus
Cmax 1402.01 nM Rattus norvegicus
F 78.0 % Rattus norvegicus
T1/2 2.2 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
SR IC50 = 0.1371 nM 9.86 SANGER: Inhibition of human SR cell growth in a cell viability assay. -
Rho-associated protein kinase 1 IC50 = 1.6 nM 8.8 Inhibition of human recombinant N-terminal his-tagged ROCK1 (3-543) expressed in... 17018693
Rho-associated protein kinase 1 IC50 = 1.6 nM 8.8 Inhibition of N-terminal His-tagged human ROCK1 (3 to 543 residues) expressed in... 31330446
Rho-associated protein kinase 1 IC50 = 1.6 nM 8.8 Inhibition of ROCK1 (unknown origin) 34388381
Rho-associated protein kinase 1 IC50 = 1.8 nM 8.74 Inhibition of human ROCK1 in Sf9 cells 17201404
Ribosomal protein S6 kinase beta-1 Ki = 3.162 nM 8.5 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
Rho-associated protein kinase 2 IC50 = 4.0 nM 8.4 Inhibition of human ROCK2 17018693
Rho-associated protein kinase 2 IC50 = 4.0 nM 8.4 Inhibition of ROCK2 (unknown origin) 34388381
KS-1 IC50 = 4.598 nM 8.34 SANGER: Inhibition of human KS-1 cell growth in a cell viability assay. -
Protein kinase C delta type Ki = 5.012 nM 8.3 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
GI-1 IC50 = 5.227 nM 8.28 SANGER: Inhibition of human GI-1 cell growth in a cell viability assay. -
BB49-HNC IC50 = 7.885 nM 8.1 SANGER: Inhibition of human BB49-HNC cell growth in a cell viability assay. -
Serine/threonine-protein kinase N2 Ki = 25.12 nM 7.6 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
Protein kinase C zeta type Ki = 25.12 nM 7.6 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
cAMP-dependent protein kinase catalytic subunit alpha Ki = 31.62 nM 7.5 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
Protein kinase C iota type Ki = 31.62 nM 7.5 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -
Rho-associated protein kinase 1 IC50 = 35.0 nM 7.46 Inhibition of N terminal histidine tagged human recombinant ROCK1 (3 to 543 resi... 33569941
Aorta IC50 = 35.0 nM 7.46 Relaxation of phenylephrine contracted Sprague-Dawley rat aortic rings 17201404
Aorta IC50 = 35.0 nM 7.46 Vasodilatory activity in Sprague-Dawley rat aorta assessed as reversal of KCl/ph... 17018693
cGMP-dependent protein kinase 2 Ki = 39.81 nM 7.4 PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 HEK-293T 346
- 10.6019/CHEMBL4689842 U2OS 341
- 10.6019/CHEMBL4689842 Fibroblast 339
17201404 10.1021/jm060873p Rattus norvegicus 14
17018693 10.1124/jpet.106.110635 Unchecked 11
33569941 10.1021/acs.jmedchem.0c01901 Rattus norvegicus 6
19740074 10.1042/bj20091035 Leucine-rich repeat serine/threonine-protein kinase 2 6
37749892 10.1021/acs.jmedchem.3c00829 N2a 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
17201404 10.1021/jm060873p Unchecked 3
19740074 10.1042/bj20091035 Unchecked 3
17018693 10.1124/jpet.106.110635 Rattus norvegicus 3
17018693 10.1124/jpet.106.110635 Aorta 3
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
17018693 10.1124/jpet.106.110635 THP-1 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
19740074 10.1042/bj20091035 Rho-associated protein kinase 2 2
33569941 10.1021/acs.jmedchem.0c01901 Rho-associated protein kinase 1 2
19740074 10.1042/bj20091035 Ephrin type-B receptor 3 1
17018693 10.1124/jpet.106.110635 Cyclin-dependent kinase 2 1

Data from ChEMBL 36 via Core Engine