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Compound Detail

CHEMBL4637208

GSK973
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CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3COC[C@@H]32)cc2c1O[C@H](CF)[C@H]2c1ccccc1

Basic Information

ChEMBL ID CHEMBL4637208
Name GSK973
Phase Preclinical
Structure Type MOL
InChI Key WZQLVEPIBAOOGF-RMMWZPCPSA-N
33
Targets
63
Activities
3
Assay Types
3
PK Parameters
20
Publications
0
Known Names

Molecular Properties

410.4
MW (Da)
2.28
ALogP
4
HBA
2
HBD
76.7
PSA (Ų)
0.79
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C23H23FN2O4
MW 410.45
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness 0.04

Activity Summary

Kd 43 meas. best 8.7
IC50 14 meas. best 7.8
Ki 6 meas. best 6.59

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bromodomain-containing protein 4
CHEMBL1163125
Kd 8.7 7.214 2.0 5
Bromodomain-containing protein 3
CHEMBL1795186
Kd 8.5 6.85 3.2 4
Bromodomain-containing protein 2
CHEMBL1293289
Kd 8.3 6.8 5.0 4
Bromodomain testis-specific protein
CHEMBL1795185
Kd 8.3 6.85 5.0 4
Unchecked
CHEMBL612545
IC50 7.8 6.6 15.8 3
Bromodomain-containing protein 4
CHEMBL1163125
IC50 7.8 6.52 15.8 5
Bromodomain-containing protein 3
CHEMBL1795186
IC50 7.8 6.15 15.8 2
Bromodomain-containing protein 2
CHEMBL1293289
IC50 7.5 5.95 31.6 2
C-C motif chemokine 2
CHEMBL1649052
IC50 7.3 7.3 50.1 1
D(3) dopamine receptor
CHEMBL234
Ki 6.59 6.59 257.0 2
Transcription initiation factor TFIID subunit 1
CHEMBL3217390
Kd 6.4 6.4 398.1 1
D(2) dopamine receptor
CHEMBL217
Ki 6.09 6.05 812.8 2
D(4) dopamine receptor
CHEMBL219
Ki 6.03 6.02 933.2 2
Transcription initiation factor TFIID subunit 1-like
CHEMBL3108641
Kd 5.7 5.7 1995.3 1
Bromodomain-containing protein 9
CHEMBL3108640
Kd 5.7 5.7 1995.3 1
Bromodomain adjacent to zinc finger domain protein 2A
CHEMBL3108642
Kd 5.5 5.5 3162.3 1
Chromatin remodeling regulator CECR2
CHEMBL3108639
Kd 5.5 5.5 3162.3 1
Bromodomain adjacent to zinc finger domain protein 2B
CHEMBL1741220
Kd 5.1 5.1 7943.3 1
Protein polybromo-1
CHEMBL1795184
Kd 5.0 4.85 10000.0 2
Probable global transcription activator SNF2L2
CHEMBL2362979
Kd 4.8 4.8 15848.9 1
Transcription activator BRG1
CHEMBL3085620
Kd 4.8 4.8 15848.9 1
Histone acetyltransferase KAT2A
CHEMBL5501
Kd 4.7 4.7 19952.6 1
CREB-binding protein
CHEMBL5747
Kd 4.6 4.6 25118.9 1
Peregrin
CHEMBL3132741
Kd 4.5 4.5 31622.8 1
Bromodomain testis-specific protein
CHEMBL1795185
IC50 4.5 4.5 31622.8 1
Histone acetyltransferase KAT2B
CHEMBL5500
Kd 4.5 4.5 31622.8 1
Histone acetyltransferase p300
CHEMBL3784
Kd 4.5 4.5 31622.8 1
Bromodomain-containing protein 8
CHEMBL3588731
Kd 4.5 4.5 31622.8 2
Bromodomain and WD repeat-containing protein 1
CHEMBL3351192
Kd 4.5 4.5 31622.8 1
ATPase family AAA domain-containing protein 2
CHEMBL2150837
Kd 4.5 4.5 31622.8 1
Bromodomain and PHD finger-containing protein 3
CHEMBL3108644
Kd 4.5 4.5 31622.8 1
E3 ubiquitin-protein ligase TRIM33
CHEMBL2176772
Kd 4.5 4.5 31622.8 1
Bromodomain-containing protein 1
CHEMBL2176774
Kd 4.5 4.5 31622.8 1
ATPase family AAA domain-containing protein 2B
CHEMBL2176775
Kd 4.5 4.5 31622.8 1
Transcription intermediary factor 1-alpha
CHEMBL3108638
Kd 4.5 4.5 31622.8 1
Bromodomain-containing protein 7
CHEMBL3085622
Kd 4.5 4.5 31622.8 1
Nucleosome-remodeling factor subunit BPTF
CHEMBL3085621
Kd 4.5 4.5 31622.8 1

Pharmacokinetic Data

Parameter Value Units Species
CL 180.0 mL.min-1.kg-1 Rattus norvegicus
CL 1.8 mL.min-1.g-1 Rattus norvegicus
F 48.0 % Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bromodomain-containing protein 4 Kd = 1.995 nM 8.7 BRD4 (BD2) DiscoverX BROMOscan -
Bromodomain-containing protein 4 Kd = 1.995 nM 8.7 BRD4 BD2 Bromoscan (DiscoverX) -
Bromodomain-containing protein 3 Kd = 3.162 nM 8.5 BRD3 (BD2) DiscoverX BROMOscan -
Bromodomain-containing protein 3 Kd = 3.162 nM 8.5 BRD3 BD2 Bromoscan (DiscoverX) -
Bromodomain-containing protein 2 Kd = 5.012 nM 8.3 BRD2 BD2 Bromoscan (DiscoverX) -
Bromodomain testis-specific protein Kd = 5.012 nM 8.3 BRDT BD2 Bromoscan (DiscoverX) -
Bromodomain-containing protein 2 Kd = 5.012 nM 8.3 BRD2 (BD2) DiscoverX BROMOscan -
Bromodomain testis-specific protein Kd = 5.012 nM 8.3 BRDT (BD2) DiscoverX BROMOscan -
Bromodomain-containing protein 4 IC50 = 15.85 nM 7.8 Inhibition of 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incu... 34260229
Bromodomain-containing protein 4 IC50 = 15.85 nM 7.8 Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (u... 34255512
Unchecked IC50 = 15.85 nM 7.8 BET mutant TR-FRET assay (BRDT BD2) -
Bromodomain-containing protein 4 IC50 = 15.85 nM 7.8 BET mutant TR-FRET assay (BRD4 BD2) -
Bromodomain-containing protein 3 IC50 = 15.85 nM 7.8 BET mutant TR-FRET assay (BRD3 BD2) -
Bromodomain-containing protein 2 IC50 = 31.62 nM 7.5 BET mutant TR-FRET assay (BRD2 BD2) -
Bromodomain-containing protein 4 Kd = 34.0 nM 7.47 BRD4 BD2 SPR -
Unchecked IC50 = 39.81 nM 7.4 BET mutant TR-FRET assay (BRDT BD2) -
C-C motif chemokine 2 IC50 = 50.12 nM 7.3 In vitro inhibition of MCP-1 in Lipopolysaccharide-stimulated human whole blood -
D(3) dopamine receptor Ki = 257.04 nM 6.59 GPCRScan assay: inhibition of D3 -
D(3) dopamine receptor Ki = 257.47 nM 6.59 GPCRScan assay: inhibition of D3 -
Transcription initiation factor TFIID subunit 1 Kd = 398.11 nM 6.4 TAF1 (2) DiscoverX BROMOscan -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL4630902 Bromodomain-containing protein 4 8
- 10.6019/CHEMBL5303304 Fibroblast 7
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.6019/CHEMBL4630902 Bromodomain-containing protein 2 6
- 10.6019/CHEMBL4630902 Bromodomain-containing protein 3 6
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
- 10.6019/CHEMBL5303304 U2OS 5
- 10.6019/CHEMBL4630902 Bromodomain testis-specific protein 5
34255512 10.1021/acs.jmedchem.1c00365 ADMET 4
- 10.6019/CHEMBL4630902 D(2) dopamine receptor 3
- 10.6019/CHEMBL4630902 Unchecked 3
34260229 10.1021/acs.jmedchem.1c00344 No relevant target 3
- 10.6019/CHEMBL5303304 HEK-293T 3
- 10.6019/CHEMBL4630902 D(3) dopamine receptor 3
- 10.6019/CHEMBL4630902 D(4) dopamine receptor 3
34255512 10.1021/acs.jmedchem.1c00365 No relevant target 3
- 10.6019/CHEMBL5608109 Hepatocyte spheroids 2
34255512 10.1021/acs.jmedchem.1c00365 Unchecked 2

Data from ChEMBL 36 via Core Engine