Compound Detail

CHEMBL494089

GSK-690693

Phase I

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Phase I

CCn1c(-c2nonc2N)nc2c(C#CC(C)(C)O)ncc(OC[C@H]3CCCNC3)c21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL494089
Name	GSK-690693
Phase	Phase I
Structure Type	MOL
InChI Key	KGPGFQWBCSZGEL-ZDUSSCGKSA-N

Known Names

GSK 690693 Gsk-690693 GSK690693

100

Targets

176

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

425.5

MW (Da)

1.58

ALogP

HBA

HBD

137.1

PSA (Å²)

0.52

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Natural Product

Extended Properties

Molecular Formula	C21H27N7O3
MW	425.49
Aromatic Rings	3
Heavy Atoms	31
NP-Likeness	-0.86

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase AKT inhibitor	INHIBITOR	Serine/threonine-protein kinase AKT	✓	✓
cAMP-dependent protein kinase (PKA) inhibitor	INHIBITOR	cAMP-dependent protein kinase (PKA)	✓	✓
Protein kinase C (PKC) inhibitor	INHIBITOR	Protein kinase C (PKC)	✓	✓

Indications

Neoplasms

Activity Summary

Kd 110 meas. best 8.68

IC50 61 meas. best 9.22

Ki 5 meas. best 9.0

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
RAC-alpha serine/threonine-protein kinase CHEMBL4282	IC50	9.22	8.071	0.6	10
RAC-alpha serine/threonine-protein kinase CHEMBL4282	Ki	9.0	9.0	1.0	2
Protein kinase C eta type CHEMBL3616	IC50	8.7	8.7	2.0	1
Protein kinase C theta type CHEMBL3920	IC50	8.7	8.7	2.0	1
RAC-beta serine/threonine-protein kinase CHEMBL2431	Kd	8.68	7.565	2.1	2
RAC-alpha serine/threonine-protein kinase CHEMBL4282	Kd	8.66	7.46	2.2	2
Protein kinase C eta type CHEMBL3616	Kd	8.62	8.62	2.4	1
RAC-gamma serine/threonine-protein kinase CHEMBL4816	Kd	8.52	7.225	3.0	2
cGMP-dependent protein kinase 2 CHEMBL2896	Kd	8.51	8.51	3.1	1
Serine/threonine-protein kinase PknB CHEMBL1908385	Kd	8.49	8.49	3.2	1
RAC-beta serine/threonine-protein kinase CHEMBL2431	Ki	8.4	8.4	4.0	2
cAMP-dependent protein kinase catalytic subunit PRKX CHEMBL5818	IC50	8.3	8.3	5.0	1
Protein kinase C epsilon type CHEMBL3582	Kd	8.28	8.28	5.3	1
Serine/threonine-protein kinase PAK 6 CHEMBL4311	IC50	8.22	8.22	6.0	1
cAMP-dependent protein kinase catalytic subunit PRKX CHEMBL5818	Kd	8.14	8.14	7.2	1
Serine/threonine-protein kinase PAK 5 CHEMBL4524	Kd	8.05	8.05	8.9	1
RAC-gamma serine/threonine-protein kinase CHEMBL4816	IC50	8.05	8.05	9.0	4
Protein kinase C theta type CHEMBL3920	Kd	8.0	7.9	10.0	2
Serine/threonine-protein kinase PAK 4 CHEMBL4482	IC50	8.0	8.0	10.0	1
RAC-beta serine/threonine-protein kinase CHEMBL2431	IC50	7.89	7.89	13.0	4
cAMP-dependent protein kinase catalytic subunit beta CHEMBL2918	Kd	7.89	7.665	13.0	2
RAC-gamma serine/threonine-protein kinase CHEMBL4816	Ki	7.89	7.89	13.0	1
Protein kinase C delta type CHEMBL2996	IC50	7.85	7.85	14.0	1
Serine/threonine-protein kinase PAK 4 CHEMBL4482	Kd	7.75	7.53	18.0	2
Protein kinase C beta type CHEMBL3045	IC50	7.72	7.72	19.0	1
cAMP-dependent protein kinase catalytic subunit alpha CHEMBL4101	Kd	7.72	7.72	19.0	1
LNCaP CHEMBL612518	IC50	7.7	7.69	20.0	2
Protein kinase C epsilon type CHEMBL3582	IC50	7.68	7.68	21.0	1
Serine/threonine-protein kinase PAK 6 CHEMBL4311	Kd	7.68	7.245	21.0	2
Unchecked CHEMBL612545	Kd	7.64	6.59	23.0	2
Unchecked CHEMBL612545	IC50	7.62	5.8733	24.0	3
cGMP-dependent protein kinase 1 CHEMBL4273	IC50	7.48	7.48	33.0	1
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	7.48	7.48	33.0	1
Serine/threonine-protein kinase N1 CHEMBL3384	Kd	7.47	7.44	34.0	2
5'-AMP-activated protein kinase catalytic subunit alpha-2 CHEMBL4637	IC50	7.3	7.3	50.0	1
BT-474 CHEMBL614529	IC50	7.3	7.23	50.0	2
Ribosomal protein S6 kinase alpha-4 CHEMBL3125	Kd	7.29	6.68	51.0	2
cAMP-dependent protein kinase type II-alpha regulatory subunit CHEMBL2221	Kd	7.28	7.28	52.0	1
Serine/threonine-protein kinase PAK 5 CHEMBL4524	IC50	7.28	7.28	52.0	1
Protein kinase C delta type CHEMBL2996	Kd	7.27	7.205	54.0	2
Serine/threonine-protein kinase LATS1 CHEMBL6167	Kd	7.13	7.13	74.0	1
5'-AMP-activated protein kinase subunit gamma-2 CHEMBL2453	Kd	7.11	7.11	78.0	1
Death-associated protein kinase 3 CHEMBL2468	IC50	7.09	7.09	81.0	1
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	7.07	7.07	86.0	1
cGMP-dependent protein kinase 1 CHEMBL4273	Kd	7.06	6.87	88.0	2
Glycogen synthase kinase-3 beta CHEMBL262	Kd	7.0	6.685	100.0	2
Serine/threonine-protein kinase DCLK3 CHEMBL6123	Kd	6.96	6.96	110.0	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	Kd	6.89	5.8943	130.0	7
Glycogen synthase kinase-3 beta CHEMBL262	IC50	6.86	6.86	138.0	1
Serine/threonine-protein kinase LATS2 CHEMBL5907	Kd	6.85	6.85	140.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	3150.0	ng.hr.mL-1	Rattus norvegicus
AUC	2010.0	ng.hr.mL-1	Canis lupus familiaris
AUC	3250.0	ng.hr.mL-1	Macaca mulatta
CL	56.7	mL.min-1.kg-1	Rattus norvegicus
CL	34.6	mL.min-1.kg-1	Canis lupus familiaris
CL	22.5	mL.min-1.kg-1	Macaca mulatta
Cmax	5005.99	nM	Rattus norvegicus
Cmax	3055.3	nM	Canis lupus familiaris
Cmax	3525.35	nM	Macaca mulatta
T1/2	8.92	hr	Rattus norvegicus
T1/2	3.5	hr	Canis lupus familiaris
T1/2	5.52	hr	Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
RAC-alpha serine/threonine-protein kinase	IC50	=	0.6	nM	9.22	Inhibition of AKT1 (unknown origin) after 1 hr by Z'-LYTE kinase assay in presen...	24900862
RAC-alpha serine/threonine-protein kinase	Ki	=	1.0	nM	9.0	Binding affinity to human AKT1	18800763
RAC-alpha serine/threonine-protein kinase	Ki	=	1.0	nM	9.0	Inhibition of AKT	19179070
RAC-alpha serine/threonine-protein kinase	IC50	=	1.7	nM	8.77	Inhibition of AKT1 (unknown origin) using biotinylated-STK as substrate after 45...	28704757
RAC-alpha serine/threonine-protein kinase	IC50	=	2.0	nM	8.7	Inhibition of AKT	19179070
RAC-alpha serine/threonine-protein kinase	IC50	=	2.0	nM	8.7	Inhibition of Akt1 (unknown origin)	33569941
RAC-alpha serine/threonine-protein kinase	IC50	=	2.0	nM	8.7	Inhibition of AKT1 (unknown origin)	38295689
Protein kinase C theta type	IC50	=	2.0	nM	8.7	Inhibition of human PKCtheta	18800763
RAC-alpha serine/threonine-protein kinase	IC50	=	2.0	nM	8.7	Inhibition of human AKT1	18800763
Protein kinase C eta type	IC50	=	2.0	nM	8.7	Inhibition of human PKCeta	18800763
RAC-beta serine/threonine-protein kinase	Kd	=	2.1	nM	8.68	Binding constant for AKT2 kinase domain	22037378
RAC-alpha serine/threonine-protein kinase	Kd	=	2.2	nM	8.66	Binding constant for AKT1 kinase domain	22037378
RAC-alpha serine/threonine-protein kinase	IC50	=	2.3	nM	8.64	Biochemical Assays: iFLiK and HTRF studies were carried out as described in Z. F...	-
Protein kinase C eta type	Kd	=	2.4	nM	8.62	Binding constant for PRKCH kinase domain	22037378
RAC-gamma serine/threonine-protein kinase	Kd	=	3.0	nM	8.52	Binding constant for AKT3 kinase domain	22037378
cGMP-dependent protein kinase 2	Kd	=	3.1	nM	8.51	Binding constant for PRKG2 kinase domain	22037378
Serine/threonine-protein kinase PknB	Kd	=	3.2	nM	8.49	Binding constant for PKNB(M.tuberculosis) kinase domain	22037378
RAC-beta serine/threonine-protein kinase	Ki	=	4.0	nM	8.4	Inhibition of AKT2	19179070
RAC-beta serine/threonine-protein kinase	Ki	=	4.0	nM	8.4	Binding affinity to human AKT2	18800763
cAMP-dependent protein kinase catalytic subunit PRKX	IC50	=	5.0	nM	8.3	Inhibition of human PrkX	18800763

Literature References

PubMed	DOI	Target Context	# Activities
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
39047611	10.1016/j.ejmech.2024.116698	A549	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
26254279	10.18632/oncotarget.4214	Serine/threonine-protein kinase AKT	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
18800763	10.1021/jm8004527	Rhesus monkey	5
30151089	10.1039/C8MD00197A	RAC-alpha serine/threonine-protein kinase	5
18800763	10.1021/jm8004527	Canis familiaris	5
18800763	10.1021/jm8004527	Rattus norvegicus	5
29191878	10.1126/science.aan4368	Unchecked	5
18800763	10.1021/jm8004527	Mus musculus	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
22037378	10.1038/nbt.1990	Proto-oncogene tyrosine-protein kinase receptor Ret	4
18800763	10.1021/jm8004527	RAC-alpha serine/threonine-protein kinase	4
18800763	10.1021/jm8004527	RAC-beta serine/threonine-protein kinase	3
22037378	10.1038/nbt.1990	Hepatocyte growth factor receptor	3
28704757	10.1016/j.ejmech.2017.06.067	Unchecked	3
22037378	10.1038/nbt.1990	Ribosomal protein S6 kinase alpha-4	2

Data from ChEMBL 36 via Core Engine