Compound Detail

CHEMBL4636881

GSK046

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CC(=O)Nc1c(F)cc(C(=O)N[C@H]2CC[C@H](O)CC2)cc1O[C@@H](C)c1ccccc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4636881
Name	GSK046
Phase	Preclinical
Structure Type	MOL
InChI Key	FRBRZGLUFOZRGD-JVPBZIDWSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

414.5

MW (Da)

3.96

ALogP

HBA

HBD

87.7

PSA (Å²)

0.67

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Unknown
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula	C23H27FN2O4
MW	414.48
Aromatic Rings	2
Heavy Atoms	30
NP-Likeness	-0.95

Activity Summary

Kd 49 meas. best 8.05

IC50 44 meas. best 7.7

EC50 2 meas. best 4.85

Ki 2 meas. best 5.46

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Bromodomain-containing protein 4 CHEMBL1163125	Kd	8.05	7.1471	9.0	7
Bromodomain testis-specific protein CHEMBL1795185	Kd	7.82	6.86	15.0	5
Bromodomain-containing protein 4 CHEMBL1163125	IC50	7.7	5.8659	19.9	17
Blood CHEMBL613416	IC50	7.5	7.5	31.6	1
Bromodomain-containing protein 3 CHEMBL1795186	Kd	7.5	6.734	32.0	5
C-C motif chemokine 2 CHEMBL1649052	IC50	7.5	7.0	31.6	4
Bromodomain-containing protein 2 CHEMBL1293289	Kd	7.46	6.7	35.0	5
Bromodomain-containing protein 3 CHEMBL1795186	IC50	7.01	5.8375	98.0	8
Bromodomain testis-specific protein CHEMBL1795185	IC50	6.7	6.0925	199.5	4
Bromodomain-containing protein 2 CHEMBL1293289	IC50	6.6	5.79	251.2	6
5-hydroxytryptamine receptor 1D CHEMBL1983	Ki	5.46	5.46	3438.8	2
Acetylcholinesterase CHEMBL220	IC50	5.1	5.1	7943.3	1
MOLM-14 CHEMBL3706570	EC50	4.85	4.85	14000.0	1
Acetylcholine receptor subunit alpha CHEMBL4808	IC50	4.6	4.6	25118.9	1
Histone acetyltransferase KAT2B CHEMBL5500	Kd	4.52	4.52	30000.0	1
Transcription intermediary factor 1-alpha CHEMBL3108638	Kd	4.52	4.52	30000.0	2
Histone acetyltransferase p300 CHEMBL3784	Kd	4.52	4.52	30000.0	1
Histone acetyltransferase KAT2A CHEMBL5501	Kd	4.52	4.52	30000.0	1
CREB-binding protein CHEMBL5747	Kd	4.52	4.52	30000.0	1
Bromodomain-containing protein 8 CHEMBL3588731	Kd	4.52	4.52	30000.0	2
Bromodomain and WD repeat-containing protein 1 CHEMBL3351192	Kd	4.52	4.52	30000.0	1
Transcription initiation factor TFIID subunit 1 CHEMBL3217390	Kd	4.52	4.52	30000.0	1
Peregrin CHEMBL3132741	Kd	4.52	4.52	30000.0	1
Bromodomain and PHD finger-containing protein 3 CHEMBL3108644	Kd	4.52	4.52	30000.0	1
Bromodomain adjacent to zinc finger domain protein 2A CHEMBL3108642	Kd	4.52	4.52	30000.0	1
Transcription initiation factor TFIID subunit 1-like CHEMBL3108641	Kd	4.52	4.52	30000.0	1
Bromodomain-containing protein 9 CHEMBL3108640	Kd	4.52	4.52	30000.0	1
Chromatin remodeling regulator CECR2 CHEMBL3108639	Kd	4.52	4.52	30000.0	1
Bromodomain adjacent to zinc finger domain protein 2B CHEMBL1741220	Kd	4.52	4.52	30000.0	1
Bromodomain-containing protein 7 CHEMBL3085622	Kd	4.52	4.52	30000.0	1
Nucleosome-remodeling factor subunit BPTF CHEMBL3085621	Kd	4.52	4.52	30000.0	1
Transcription activator BRG1 CHEMBL3085620	Kd	4.52	4.52	30000.0	1
Probable global transcription activator SNF2L2 CHEMBL2362979	Kd	4.52	4.52	30000.0	1
ATPase family AAA domain-containing protein 2B CHEMBL2176775	Kd	4.52	4.52	30000.0	1
Bromodomain-containing protein 1 CHEMBL2176774	Kd	4.52	4.52	30000.0	1
E3 ubiquitin-protein ligase TRIM33 CHEMBL2176772	Kd	4.52	4.52	30000.0	1
ATPase family AAA domain-containing protein 2 CHEMBL2150837	Kd	4.52	4.52	30000.0	1
Protein polybromo-1 CHEMBL1795184	Kd	4.52	4.52	30000.0	2
Adenosine receptor A2a CHEMBL251	EC50	4.5	4.5	31622.8	1
Unchecked CHEMBL612545	IC50	4.3	4.3	50118.7	1
Voltage-dependent L-type calcium channel subunit alpha-1C CHEMBL1940	IC50	4.0	4.0	100000.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	36.0	%	Canis lupus familiaris
CL	46.0	%	Rattus norvegicus
CL	20.0	mL.min-1.kg-1	Canis lupus familiaris
CL	36.0	mL.min-1.kg-1	Rattus norvegicus
CL	82.0	mL.min-1.kg-1	Rattus norvegicus
F	66.0	%	Canis lupus familiaris
F	31.0	%	Rattus norvegicus
F	31.0	%	Rattus norvegicus
Fu	0.32	-	Homo sapiens
Fu	0.33	-	Canis lupus familiaris
Fu	0.44	-	Rattus norvegicus
T1/2	0.7	hr	Canis lupus familiaris
T1/2	0.5	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Bromodomain-containing protein 4	Kd	=	9.0	nM	8.05	BRD4(1,2) DiscoverX BROMOscan	-
Bromodomain-containing protein 4	Kd	=	9.0	nM	8.05	BRD4(2) DiscoverX BROMOscan	-
Bromodomain-containing protein 4	Kd	=	9.0	nM	8.05	BRD4 BD2 Bromoscan (DiscoverX)	-
Bromodomain testis-specific protein	Kd	=	15.0	nM	7.82	BRDT(2) DiscoverX BROMOscan	-
Bromodomain testis-specific protein	Kd	=	15.0	nM	7.82	BRDT BD2 Bromoscan (DiscoverX)	-
Bromodomain-containing protein 4	IC50	=	19.95	nM	7.7	Inhibition of BRD4 BD2 (unknown origin) by TR-FRET assay	37736196
Bromodomain-containing protein 4	Kd	=	30.0	nM	7.52	BRD4 BD2 SPR	-
C-C motif chemokine 2	IC50	=	31.62	nM	7.5	Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound ...	37736196
Blood	IC50	=	31.62	nM	7.5	Inhibition of LPS-induced MCP1 production in human whole blood preincubated for ...	32691591
C-C motif chemokine 2	IC50	=	31.62	nM	7.5	LPS-PBMC assay (MCP-1)	-
Bromodomain-containing protein 3	Kd	=	32.0	nM	7.5	BRD3 BD2 Bromoscan (DiscoverX)	-
Bromodomain-containing protein 3	Kd	=	33.0	nM	7.48	BRD3(2) DiscoverX BROMOscan	-
Bromodomain-containing protein 2	Kd	=	35.0	nM	7.46	BRD2 BD2 Bromoscan (DiscoverX)	-
Bromodomain-containing protein 2	Kd	=	35.0	nM	7.46	BRD2(2) DiscoverX BROMOscan	-
Bromodomain testis-specific protein	Kd	=	36.0	nM	7.44	BRDT(1,2) DiscoverX BROMOscan	-
Bromodomain-containing protein 3	Kd	=	47.0	nM	7.33	BRD3(1,2) DiscoverX BROMOscan	-
Bromodomain-containing protein 4	IC50	=	49.0	nM	7.31	TR-FRET assay (BRD4 BD2)	-
Bromodomain-containing protein 4	IC50	=	49.0	nM	7.31	Inhibition of BRD4 BD2 (unknown origin) by TR-FRET assay	38295759
Bromodomain-containing protein 4	IC50	=	50.12	nM	7.3	Displacement of Alexa Fluor 647 labelled ligand from 6His-Thr tagged BRD4 BD2/BD...	34232650
Bromodomain-containing protein 4	IC50	=	50.12	nM	7.3	Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD2 domain Y390A mutant (u...	32702236

Literature References

PubMed	DOI	Target Context	# Activities
32691591	10.1021/acs.jmedchem.0c00605	ADMET	17
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL4630908	Bromodomain-containing protein 4	12
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
-	10.6019/CHEMBL5303304	U2OS	10
-	10.6019/CHEMBL4630908	Bromodomain-containing protein 3	9
-	10.6019/CHEMBL4630908	Bromodomain testis-specific protein	9
-	10.6019/CHEMBL5303304	Fibroblast	9
-	10.6019/CHEMBL4630908	Bromodomain-containing protein 2	9
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
-	10.6019/CHEMBL5303304	HEK-293T	6
-	10.6019/CHEMBL4630908	GABA-A receptor; anion channel	5
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
37736196	10.1021/acsmedchemlett.3c00242	Bromodomain-containing protein 4	5
34255512	10.1021/acs.jmedchem.1c00365	ADMET	4
34232650	10.1021/acs.jmedchem.0c02155	Bromodomain-containing protein 4	3
-	10.6019/CHEMBL4630908	5-hydroxytryptamine receptor 3A	3
32691591	10.1021/acs.jmedchem.0c00605	Bromodomain-containing protein 4	3
-	10.6019/CHEMBL4630908	5-hydroxytryptamine receptor 1D	3
-	10.6019/CHEMBL4630908	5-hydroxytryptamine receptor 2C	3

Data from ChEMBL 36 via Core Engine