Compound Detail

CHEMBL1908394

GSK-461364

Phase I

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Phase I

C[C@@H](Oc1cc(-n2cnc3ccc(CN4CCN(C)CC4)cc32)sc1C(N)=O)c1ccccc1C(F)(F)F

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1908394
Name	GSK-461364
Phase	Phase I
Structure Type	MOL
InChI Key	ZHJGWYRLJUCMRT-QGZVFWFLSA-N

Known Names

Gsk 461364 Gsk-461364 GSK-461364A GSK461364

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

543.6

MW (Da)

5.09

ALogP

HBA

HBD

76.6

PSA (Å²)

0.35

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Extended Properties

Molecular Formula	C27H28F3N5O2S
MW	543.62
Aromatic Rings	4
Heavy Atoms	38
NP-Likeness	-1.37

Mechanism of Action

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

Indications

Lymphoma, Non-Hodgkin

Activity Summary

Kd 79 meas. best 10.03

IC50 5 meas. best 9.0

Ki 5 meas. best 8.66

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Serine/threonine-protein kinase PLK1 CHEMBL3024	Kd	10.03	10.03	0.1	1
HEK-293T CHEMBL3706568	IC50	9.0	9.0	1.0	1
MDA-MB-231 CHEMBL400	IC50	9.0	9.0	1.0	1
MM1.S CHEMBL4296471	IC50	9.0	9.0	1.0	1
Serine/threonine-protein kinase PLK1 CHEMBL3024	Ki	8.66	8.66	2.2	3
HUVEC CHEMBL613979	IC50	8.15	8.15	7.0	1
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	7.64	7.64	23.0	2
Serine/threonine-protein kinase 10 CHEMBL3981	Kd	7.16	6.48	69.0	2
Mitogen-activated protein kinase kinase kinase 1 CHEMBL3956	Kd	6.97	6.395	106.0	2
Serine/threonine-protein kinase Nek2 CHEMBL3835	IC50	6.8	6.8	158.0	1
Ribosomal protein S6 kinase alpha-3 CHEMBL2345	Kd	6.72	6.72	190.0	1
Serine/threonine-protein kinase pim-1 CHEMBL2147	Kd	6.6	6.6	250.0	1
Serine/threonine-protein kinase Nek2 CHEMBL3835	Kd	6.58	6.58	260.0	2
Ribosomal protein S6 kinase alpha-6 CHEMBL4924	Kd	6.46	6.46	350.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.39	6.0657	410.0	7
BMP-2-inducible protein kinase CHEMBL4522	Kd	6.33	5.87	470.0	2
Serine/threonine-protein kinase PLK2 CHEMBL5938	Kd	6.3	6.3	500.0	1
Calcium/calmodulin-dependent protein kinase type II subunit delta CHEMBL2801	Kd	6.21	6.21	620.0	1
Serine/threonine-protein kinase N2 CHEMBL3032	Kd	6.21	6.21	620.0	1
Serine/threonine-protein kinase PLK3 CHEMBL4897	Kd	6.13	6.13	740.0	1
Ribosomal protein S6 kinase alpha-4 CHEMBL3125	Kd	6.13	6.13	740.0	1
Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha CHEMBL5969	Kd	6.11	6.11	770.0	1
Serine/threonine-protein kinase PLK2 CHEMBL5938	Ki	6.07	6.07	860.0	1
Casein kinase II subunit alpha' CHEMBL4070	Kd	6.0	6.0	990.0	1
Calcium/calmodulin-dependent protein kinase type II subunit alpha CHEMBL4147	Kd	6.0	6.0	1000.0	1
Serine/threonine-protein kinase PLK3 CHEMBL4897	Ki	6.0	6.0	1000.0	1
Serine/threonine-protein kinase Nek9 CHEMBL5257	Kd	5.96	5.96	1100.0	1
Serine/threonine-protein kinase pim-3 CHEMBL5407	Kd	5.96	5.96	1100.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	5.96	5.78	1100.0	2
Serine/threonine-protein kinase Nek5 CHEMBL5044	Kd	5.96	5.96	1100.0	1
Ribosomal protein S6 kinase alpha-2 CHEMBL3906	Kd	5.92	5.92	1200.0	1
Calcium/calmodulin-dependent protein kinase type II subunit gamma CHEMBL3829	Kd	5.89	5.89	1300.0	1
Tyrosine-protein kinase receptor Tie-1 CHEMBL5274	Kd	5.85	5.85	1400.0	1
Death-associated protein kinase 1 CHEMBL2558	Kd	5.85	5.85	1400.0	1
Serine/threonine-protein kinase ULK2 CHEMBL5435	Kd	5.85	5.85	1400.0	1
Serine/threonine-protein kinase TAO3 CHEMBL5701	Kd	5.85	5.85	1400.0	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	Kd	5.8	5.47	1600.0	2
Serine/threonine-protein kinase Nek1 CHEMBL5855	Kd	5.75	5.75	1800.0	1
Serine/threonine-protein kinase D3 CHEMBL2595	Kd	5.72	5.72	1900.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	Kd	5.72	5.72	1900.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	Kd	5.7	5.7	2000.0	1
Serine/threonine-protein kinase RIO3 CHEMBL5659	Kd	5.64	5.6267	2300.0	3
Adenosine kinase CHEMBL3589	Kd	5.6	5.6	2507.0	1
G protein-coupled receptor kinase 4 CHEMBL5861	Kd	5.55	5.55	2800.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta CHEMBL5554	Kd	5.55	5.55	2800.0	1
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	5.55	5.55	2800.0	1
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma CHEMBL1770034	Kd	5.55	5.55	2837.0	1
Calcium/calmodulin-dependent protein kinase type II subunit beta CHEMBL4121	Kd	5.54	5.54	2900.0	1
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	5.54	5.54	2900.0	1
Death-associated protein kinase 2 CHEMBL3123	Kd	5.54	5.54	2900.0	1

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Serine/threonine-protein kinase PLK1	Kd	=	0.094	nM	10.03	Binding constant for PLK1 kinase domain	22037378
MDA-MB-231	IC50	=	1.0	nM	9.0	Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs ...	28792760
MM1.S	IC50	=	1.0	nM	9.0	Antiproliferative activity against human MM1S cells measured after 72 hrs by Cel...	28792760
HEK-293T	IC50	=	1.0	nM	9.0	Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTi...	28792760
Serine/threonine-protein kinase PLK1	Ki	=	2.2	nM	8.66	Inhibition of PLK1 (unknown origin)	32631534
Serine/threonine-protein kinase PLK1	Ki	=	2.2	nM	8.66	Binding affinity to PLK1 (unknown origin) assessed as inhibition constant	33356242
Serine/threonine-protein kinase PLK1	Ki	=	2.2	nM	8.66	Inhibition of human recombinant His6-tagged PLK1 (1 to 603 residues) using casei...	28792760
HUVEC	IC50	=	7.0	nM	8.15	Cytotoxicity against human HUVEC cells assessed as inhibition of cell growth inc...	19690138
NUAK family SNF1-like kinase 2	Kd	=	23.0	nM	7.64	Binding affinity to NUAK2 (unknown origin) assessed as dissociation constant	33356242
NUAK family SNF1-like kinase 2	Kd	=	23.0	nM	7.64	Binding constant for SNARK kinase domain	22037378
Serine/threonine-protein kinase 10	Kd	=	69.0	nM	7.16	Binding constant for LOK kinase domain	22037378
Mitogen-activated protein kinase kinase kinase 1	Kd	=	106.0	nM	6.97	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Serine/threonine-protein kinase Nek2	IC50	=	158.0	nM	6.8	Selectivity interaction (Kinase panel (GlaxoSmithKline)) EUB0000603a NEK2	-
Ribosomal protein S6 kinase alpha-3	Kd	=	190.0	nM	6.72	Binding constant for RSK2(Kin.Dom.1-N-terminal) kinase domain	22037378
Serine/threonine-protein kinase pim-1	Kd	=	250.0	nM	6.6	Binding constant for PIM1 kinase domain	22037378
Serine/threonine-protein kinase Nek2	Kd	=	260.0	nM	6.58	Binding constant for NEK2 kinase domain	22037378
Serine/threonine-protein kinase Nek2	Kd	=	260.0	nM	6.58	Inhibition of NEK2 (unknown origin) assessed as dissociation constant	30108900
Ribosomal protein S6 kinase alpha-6	Kd	=	350.0	nM	6.46	Binding constant for RSK4(Kin.Dom.1-N-terminal) kinase domain	22037378
Receptor-type tyrosine-protein kinase FLT3	Kd	=	410.0	nM	6.39	Binding constant for FLT3(D835H) kinase domain	22037378
Receptor-type tyrosine-protein kinase FLT3	Kd	=	430.0	nM	6.37	Binding constant for FLT3(D835Y) kinase domain	22037378

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	Fibroblast	345
-	10.6019/CHEMBL4689842	HEK-293T	344
-	10.6019/CHEMBL4689842	U2OS	342
19690138	10.1158/0008-5472.can-09-0945	COLO 205	18
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
19690138	10.1158/0008-5472.can-09-0945	A549	8
19690138	10.1158/0008-5472.can-09-0945	ZR-75-1	7
19690138	10.1158/0008-5472.can-09-0945	Unchecked	7
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
19690138	10.1158/0008-5472.can-09-0945	U2OS	6
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
29191878	10.1126/science.aan4368	Unchecked	5
19690138	10.1158/0008-5472.can-09-0945	MDA-MB-468	4
19690138	10.1158/0008-5472.can-09-0945	HT-29	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4

Data from ChEMBL 36 via Core Engine