Compound Detail

CHEMBL558642

GSK-650394

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O=C(O)c1ccc(-c2c[nH]c3ncc(-c4ccccc4)cc23)cc1C1CCCC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL558642
Name	GSK-650394
Phase	Preclinical
Structure Type	MOL
InChI Key	WVSBGSNVCDAMCF-UHFFFAOYSA-N

395

Targets

672

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

382.5

MW (Da)

6.25

ALogP

HBA

HBD

66.0

PSA (Å²)

0.44

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C25H22N2O2
MW	382.46
Aromatic Rings	4
Heavy Atoms	29
NP-Likeness	-0.16

Activity Summary

IC50 671 meas. best 8.64

Kd 1 meas. best 6.53

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Calcium/calmodulin-dependent protein kinase kinase 2 CHEMBL5284	IC50	8.64	8.42	2.3	3
Calcium/calmodulin-dependent protein kinase kinase 1 CHEMBL5256	IC50	8.51	7.995	3.1	2
Serine/threonine-protein kinase Sgk1 CHEMBL2343	IC50	7.89	7.34	13.0	3
MV4-11 CHEMBL613835	IC50	6.78	6.78	164.9	1
Aurora kinase A CHEMBL4722	Kd	6.53	6.53	298.0	1
Daoy CHEMBL612519	IC50	6.29	6.29	515.3	1
BFTC-905 CHEMBL1075396	IC50	6.11	6.11	784.5	1
KM12 CHEMBL614709	IC50	6.07	6.07	850.7	1
GDM-1 CHEMBL2366157	IC50	6.06	6.06	879.4	1
RT-112 CHEMBL614145	IC50	5.99	5.99	1027.8	1
MONO-MAC-6 CHEMBL2366062	IC50	5.93	5.93	1181.0	1
Calcium/calmodulin-dependent protein kinase kinase 2 CHEMBL4295888	IC50	5.9	5.9	1258.9	1
HGC-27 CHEMBL1075463	IC50	5.88	5.88	1308.2	1
HuTu80 CHEMBL614582	IC50	5.88	5.88	1301.7	1
LCLC-97TM1 CHEMBL1075489	IC50	5.86	5.86	1367.7	1
HLE CHEMBL1075464	IC50	5.85	5.85	1426.8	1
LXF-289 cell line CHEMBL614107	IC50	5.85	5.85	1401.5	1
RKO CHEMBL614879	IC50	5.8	5.8	1579.7	1
SNG-M CHEMBL1075582	IC50	5.75	5.75	1798.5	1
MCF7 CHEMBL387	IC50	5.74	5.74	1817.8	1
BC-3 CHEMBL2366371	IC50	5.73	5.73	1870.9	1
A-431 CHEMBL614069	IC50	5.73	5.73	1859.0	1
A-427 CHEMBL614515	IC50	5.73	5.73	1876.1	1
SW-620 CHEMBL612262	IC50	5.71	5.71	1928.2	1
HOS CHEMBL614736	IC50	5.71	5.71	1973.1	1
MFH-ino CHEMBL2366262	IC50	5.7	5.7	1986.6	1
TE-12 CHEMBL2366278	IC50	5.7	5.7	1991.3	1
KYSE-180 CHEMBL1075485	IC50	5.69	5.69	2061.3	1
CGTH-W-1 CHEMBL2366300	IC50	5.68	5.68	2096.4	1
KYSE-510 CHEMBL613868	IC50	5.67	5.67	2130.9	1
NCI-H2342 CHEMBL1075537	IC50	5.66	5.66	2190.5	1
KU812 cell line CHEMBL613997	IC50	5.66	5.66	2187.1	1
PSN1 CHEMBL614241	IC50	5.66	5.66	2185.5	1
BB30-HNC CHEMBL2366271	IC50	5.63	5.63	2331.7	1
KYSE-270 CHEMBL1075486	IC50	5.62	5.62	2413.6	1
BC1 cell line CHEMBL614277	IC50	5.6	5.6	2516.5	1
TE-15 CHEMBL2366086	IC50	5.59	5.59	2591.8	1
T84 CHEMBL613531	IC50	5.58	5.58	2604.5	1
CAL-12T CHEMBL1075406	IC50	5.57	5.57	2711.6	1
SW1710 CHEMBL1075590	IC50	5.57	5.57	2700.8	1
NKM-1 CHEMBL2366133	IC50	5.56	5.56	2767.3	1
OCUB-M CHEMBL2366121	IC50	5.55	5.55	2788.6	1
786-0 CHEMBL613102	IC50	5.53	5.53	2948.2	1
EW-13 CHEMBL2366124	IC50	5.52	5.52	3015.6	1
5637 CHEMBL612565	IC50	5.49	5.49	3206.7	1
NCI-H2122 CHEMBL1075533	IC50	5.48	5.48	3333.0	1
PA-1 CHEMBL614949	IC50	5.48	5.48	3330.8	1
NCI-H460 CHEMBL396	IC50	5.47	5.47	3404.1	1
CHL-1 CHEMBL1075422	IC50	5.46	5.46	3496.7	1
MOLT-16 CHEMBL2366362	IC50	5.45	5.45	3515.6	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	313.0	ng.hr.mL-1	Rattus norvegicus
AUC	134.0	ng.hr/ml/mg/kg	Rattus norvegicus
CL	25.7	mL.min-1.kg-1	Rattus norvegicus
T1/2	1.583	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Calcium/calmodulin-dependent protein kinase kinase 2	IC50	=	2.3	nM	8.64	Inhibition of CaMKK2 (161 to 449 residues) (unknown origin) expressed in Escheri...	38009718
Calcium/calmodulin-dependent protein kinase kinase 2	IC50	=	3.0	nM	8.52	Inhibition of human CAMKK2 using CAMKKtide as substrate assessed as residual act...	34264658
Calcium/calmodulin-dependent protein kinase kinase 1	IC50	=	3.1	nM	8.51	Inhibition of CaMKK1 (unknown origin) incubated for 20 mins in presence of kinas...	38009718
Calcium/calmodulin-dependent protein kinase kinase 2	IC50	=	7.943	nM	8.1	Inhibition of full-length human GST-tagged CAMKK2 using 5FAM-AKPKGNKDYHLQTCCGSLA...	29653895
Serine/threonine-protein kinase Sgk1	IC50	=	13.0	nM	7.89	Inhibition of SGK1 by fluorescence polarization assay	19497745
Serine/threonine-protein kinase Sgk1	IC50	=	13.0	nM	7.89	Inhibition of SGK1 expressed in Escherichia coli or baculovirus-infected insect ...	21699136
Calcium/calmodulin-dependent protein kinase kinase 1	IC50	=	33.0	nM	7.48	Inhibition of human CAMKK1 using CAMKKtide as substrate assessed as residual act...	34264658
MV4-11	IC50	=	164.9	nM	6.78	SANGER: Inhibition of human MV-4-11 cell growth in a cell viability assay.	-
Aurora kinase A	Kd	=	298.01	nM	6.53	Further kinetic evaluation of compounds supplied by Sanofi against AuroraA withi...	-
Daoy	IC50	=	515.32	nM	6.29	SANGER: Inhibition of human Daoy cell growth in a cell viability assay.	-
Serine/threonine-protein kinase Sgk1	IC50	=	580.0	nM	6.24	Inhibition of SGK1-mediated epithelial sodium channel activity in human M-1 cell...	19497745
BFTC-905	IC50	=	784.55	nM	6.11	SANGER: Inhibition of human BFTC-905 cell growth in a cell viability assay.	-
KM12	IC50	=	850.69	nM	6.07	SANGER: Inhibition of human KM12 cell growth in a cell viability assay.	-
GDM-1	IC50	=	879.37	nM	6.06	SANGER: Inhibition of human GDM-1 cell growth in a cell viability assay.	-
RT-112	IC50	=	1027.82	nM	5.99	SANGER: Inhibition of human RT-112 cell growth in a cell viability assay.	-
MONO-MAC-6	IC50	=	1180.97	nM	5.93	SANGER: Inhibition of human MONO-MAC-6 cell growth in a cell viability assay.	-
Calcium/calmodulin-dependent protein kinase kinase 2	IC50	=	1258.93	nM	5.9	Inhibition of CAMKK2 in mouse N39 cells assessed as decrease in AMPKalpha phosph...	29653895
HuTu80	IC50	=	1301.72	nM	5.88	SANGER: Inhibition of human HUTU-80 cell growth in a cell viability assay.	-
HGC-27	IC50	=	1308.21	nM	5.88	SANGER: Inhibition of human HGC-27 cell growth in a cell viability assay.	-
LCLC-97TM1	IC50	=	1367.68	nM	5.86	SANGER: Inhibition of human LCLC-97TM1 cell growth in a cell viability assay.	-

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL5724696	U2OS	8
-	10.6019/CHEMBL5303304	Fibroblast	7
-	10.6019/CHEMBL5303304	U2OS	7
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
19497745	10.1016/j.bmcl.2009.05.051	Rattus norvegicus	5
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
34264658	10.1021/acs.jmedchem.0c02274	Calcium/calmodulin-dependent protein kinase kinase 2	5
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
-	10.6019/CHEMBL3885741	Aurora kinase A	3
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
22858098	10.1016/j.bmcl.2012.06.096	Serine/threonine-protein kinase Sgk1	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
-	10.6019/CHEMBL5303304	HEK-293T	2
19497745	10.1016/j.bmcl.2009.05.051	Serine/threonine-protein kinase Sgk1	2
29653895	10.1016/j.bmcl.2018.03.034	Calcium/calmodulin-dependent protein kinase kinase 2	2
-	10.6019/CHEMBL1201861	EHEB	1
-	10.6019/CHEMBL1201861	EKVX	1
-	10.1021/acschembio.2c00877	Colon organoid	1

Data from ChEMBL 36 via Core Engine