Compound Detail

CHEMBL4639128

GSK778

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COCc1nc2cnc3cc(-c4c(C)noc4C)c(OC[C@H]4CCNC4)cc3c2n1[C@H](C)c1ccccc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4639128
Name	GSK778
Phase	Preclinical
Structure Type	MOL
InChI Key	ZORLJXWXFABTPZ-CTNGQTDRSA-N

Targets

109

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

511.6

MW (Da)

5.60

ALogP

HBA

HBD

87.2

PSA (Å²)

0.29

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	C30H33N5O3
MW	511.63
Aromatic Rings	5
Heavy Atoms	38
NP-Likeness	-0.92

Activity Summary

IC50 55 meas. best 7.4

Kd 44 meas. best 9.2

Ki 10 meas. best 6.39

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Bromodomain-containing protein 4 CHEMBL1163125	Kd	9.2	7.5264	0.6	11
Bromodomain-containing protein 3 CHEMBL1795186	Kd	8.3	7.7033	5.0	3
Bromodomain-containing protein 2 CHEMBL1293289	Kd	7.89	7.2867	13.0	3
Bromodomain testis-specific protein CHEMBL1795185	Kd	7.75	6.9233	18.0	3
C-C motif chemokine 2 CHEMBL1649052	IC50	7.4	7.1	39.8	2
Bromodomain-containing protein 4 CHEMBL1163125	IC50	7.4	6.5219	39.8	16
PBMC CHEMBL613107	IC50	7.4	7.3	39.8	2
Bromodomain-containing protein 3 CHEMBL1795186	IC50	7.4	6.685	39.8	6
Bromodomain-containing protein 2 CHEMBL1293289	IC50	7.12	6.2867	75.0	6
MV4-11 CHEMBL613835	IC50	7.0	7.0	100.0	2
Bromodomain testis-specific protein CHEMBL1795185	IC50	6.84	5.8	143.0	6
Blood CHEMBL613416	IC50	6.8	6.7	158.5	2
D(3) dopamine receptor CHEMBL234	Ki	6.39	6.35	407.4	2
D(4) dopamine receptor CHEMBL219	Ki	6.09	6.08	812.8	2
Acetylcholine receptor subunit alpha CHEMBL4808	IC50	6.0	6.0	1000.0	1
Cytochrome P450 3A4 CHEMBL340	IC50	6.0	5.6	1000.0	2
GABA-A receptor; anion channel CHEMBL1907607	Ki	5.81	5.7675	1548.8	4
D(2) dopamine receptor CHEMBL217	IC50	5.5	5.5	3162.3	1
CREB-binding protein CHEMBL5747	Kd	5.42	5.42	3800.0	1
5-hydroxytryptamine receptor 3A CHEMBL1899	Ki	5.35	5.35	4456.5	2
Histone acetyltransferase p300 CHEMBL3784	Kd	5.24	5.24	5700.0	1
Muscarinic acetylcholine receptor M2 CHEMBL211	IC50	5.0	5.0	10000.0	1
Peregrin CHEMBL3132741	Kd	4.82	4.82	15000.0	1
Sodium-dependent noradrenaline transporter CHEMBL222	IC50	4.7	4.7	19952.6	1
ATPase family AAA domain-containing protein 2B CHEMBL2176775	Kd	4.6	4.6	25000.0	1
Protein polybromo-1 CHEMBL1795184	Kd	4.54	4.53	29000.0	2
Histone acetyltransferase KAT2A CHEMBL5501	Kd	4.52	4.52	30000.0	1
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
Bromodomain adjacent to zinc finger domain protein 2B CHEMBL1741220	Kd	4.52	4.52	30000.0	1
Nucleosome-remodeling factor subunit BPTF CHEMBL3085621	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
Transcription intermediary factor 1-alpha CHEMBL3108638	Kd	4.52	4.52	30000.0	2
Bromodomain-containing protein 7 CHEMBL3085622	Kd	4.52	4.52	30000.0	1
Probable global transcription activator SNF2L2 CHEMBL2362979	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
Histone acetyltransferase KAT2B CHEMBL5500	Kd	4.48	4.48	33000.0	1
3',5'-cyclic-AMP phosphodiesterase 4B CHEMBL275	IC50	4.4	4.4	39810.7	1
Voltage-gated inwardly rectifying potassium channel KCNH2 CHEMBL240	IC50	4.4	4.4	39810.7	1
Sodium-dependent serotonin transporter CHEMBL228	IC50	4.4	4.4	39810.7	1
Solute carrier organic anion transporter family member 1B1 CHEMBL1697668	IC50	4.4	4.4	39810.7	1
Sodium channel protein type 5 subunit alpha CHEMBL1980	IC50	4.3	4.3	50118.7	1
Acetylcholinesterase CHEMBL220	IC50	4.2	4.2	63095.7	1
Amine oxidase [flavin-containing] B CHEMBL2039	IC50	4.1	4.1	79432.8	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1708.84	ng.hr.mL-1	Mus musculus
Cmax	2400.0	nM	Mus musculus
Fu	0.08	-	Mus musculus
T1/2	0.9	hr	Mus musculus
T1/2	8.2	hr	Mus musculus
Tmax	0.25	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Bromodomain-containing protein 4	Kd	=	0.63	nM	9.2	Binding affinity to human partial length BRD4 BD2 expressed in bacterial express...	34236185
Bromodomain-containing protein 3	Kd	=	5.0	nM	8.3	BRD3(1) DiscoverX BROMOscan	-
Bromodomain-containing protein 3	Kd	=	5.0	nM	8.3	BRD3 Bromoscan (DiscoverX)	-
Bromodomain-containing protein 4	Kd	=	5.9	nM	8.23	BRD4(1) DiscoverX BROMOscan	-
Bromodomain-containing protein 4	Kd	=	5.9	nM	8.23	BRD4 Bromoscan (DiscoverX)	-
Bromodomain-containing protein 4	Kd	=	6.3	nM	8.2	Binding affinity to BRD4 BD1 (unknown origin) assessed as dissociation constant ...	34236185
Bromodomain-containing protein 4	Kd	=	10.0	nM	8.0	BRD4 BD1 SPR	-
Bromodomain-containing protein 4	Kd	=	10.0	nM	8.0	Binding affinity to N-terminal His6-tagged human BRD4 BD1 (1 to 477 residues)/BD...	32787145
Bromodomain-containing protein 4	Kd	=	11.0	nM	7.96	BRD4(FULL-LENGTH,SHORT-ISO.) DiscoverX BROMOscan	-
Bromodomain-containing protein 2	Kd	=	13.0	nM	7.89	BRD2(1) DiscoverX BROMOscan	-
Bromodomain-containing protein 2	Kd	=	13.0	nM	7.89	BRD2 Bromoscan (DiscoverX)	-
Bromodomain testis-specific protein	Kd	=	18.0	nM	7.75	BRDT Bromoscan (DiscoverX)	-
Bromodomain testis-specific protein	Kd	=	18.0	nM	7.75	BRDT(1) DiscoverX BROMOscan	-
Bromodomain-containing protein 4	IC50	=	39.81	nM	7.4	Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged hu...	32787145
Bromodomain-containing protein 3	IC50	=	39.81	nM	7.4	Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged hu...	32787145
PBMC	IC50	=	39.81	nM	7.4	Antiinflammatory activity in human PBMC assessed as reduction in LPS-induced MCP...	32787145
C-C motif chemokine 2	IC50	=	39.81	nM	7.4	Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound ...	37736196
Bromodomain-containing protein 4	IC50	=	39.81	nM	7.4	Inhibition of BRD4 BD1 (unknown origin) by TR-FRET assay	37736196
Bromodomain-containing protein 3	IC50	=	39.81	nM	7.4	BET mutant TR-FRETassay (BRD3 BD1)	-
Bromodomain-containing protein 4	IC50	=	39.81	nM	7.4	BET mutant TR-FRET assay (BRD4 BD1)	-

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL4630907	Bromodomain-containing protein 4	12
-	10.6019/CHEMBL5303304	U2OS	9
-	10.6019/CHEMBL4630907	Bromodomain testis-specific protein	7
-	10.6019/CHEMBL4630907	Bromodomain-containing protein 3	7
-	10.6019/CHEMBL4630907	Bromodomain-containing protein 2	7
-	10.6019/CHEMBL4630907	GABA-A receptor; anion channel	6
32787145	10.1021/acs.jmedchem.0c00566	ADMET	6
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
-	10.6019/CHEMBL5303304	Fibroblast	6
32787145	10.1021/acs.jmedchem.0c00566	Bromodomain-containing protein 4	6
32787145	10.1021/acs.jmedchem.0c00566	Unchecked	5
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
-	10.6019/CHEMBL4630907	5-hydroxytryptamine receptor 3A	5
37736196	10.1021/acsmedchemlett.3c00242	Bromodomain-containing protein 4	5
-	10.6019/CHEMBL4630907	D(3) dopamine receptor	3
-	10.6019/CHEMBL4630907	D(4) dopamine receptor	3
-	10.6019/CHEMBL4630907	Kappa-type opioid receptor	3
-	10.6019/CHEMBL4630907	Beta-2 adrenergic receptor	3

Data from ChEMBL 36 via Core Engine