Compound Detail

CHEMBL2171124

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Cn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(C(F)(F)F)c2)c2c(N)ncnc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL2171124
Phase	Preclinical
Structure Type	MOL
InChI Key	SIXVRXARNAVBTC-UHFFFAOYSA-N

Known Names

GSK2606414

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

451.4

MW (Da)

4.37

ALogP

HBA

HBD

77.0

PSA (Å²)

0.50

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C24H20F3N5O
MW	451.45
Aromatic Rings	4
Heavy Atoms	33
NP-Likeness	-1.20

Activity Summary

IC50 40 meas. best 9.4

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Unchecked CHEMBL612545	IC50	9.4	8.98	0.4	3
L929 CHEMBL612267	IC50	9.4	9.4	0.4	1
Eukaryotic translation initiation factor 2-alpha kinase 3 CHEMBL6030	IC50	9.4	9.4	0.4	2
MEF CHEMBL614342	IC50	8.14	8.14	7.3	1
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	IC50	7.75	7.745	18.0	2
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	6.81	6.81	154.0	1
SARS-CoV-2 CHEMBL4303835	IC50	6.6	6.6	250.0	1
Aurora kinase B CHEMBL2185	IC50	6.39	6.39	407.0	1
Eukaryotic translation initiation factor 2-alpha kinase 1 CHEMBL6029	IC50	6.38	6.38	420.0	1
Protein-tyrosine kinase 6 CHEMBL4601	IC50	6.38	6.38	412.0	1
Mitogen-activated protein kinase kinase kinase 10 CHEMBL2873	IC50	6.34	6.34	452.0	1
Tyrosine-protein kinase Mer CHEMBL5331	IC50	6.32	6.32	474.0	1
Discoidin domain-containing receptor 2 CHEMBL5122	IC50	6.28	6.28	524.0	1
Toxoplasma gondii CHEMBL612888	IC50	6.21	6.21	620.0	1
Interferon-induced, double-stranded RNA-activated protein kinase CHEMBL5785	IC50	6.16	6.16	696.0	1
Myosin light chain kinase 2, skeletal/cardiac muscle CHEMBL2777	IC50	6.15	6.15	701.0	1
Cytochrome P450 2C8 CHEMBL3721	IC50	6.05	6.05	890.0	1
Inhibitor of nuclear factor kappa-B kinase subunit epsilon CHEMBL3529	IC50	5.97	5.97	1064.0	1
NT-3 growth factor receptor CHEMBL5608	IC50	5.95	5.95	1115.0	1
Mitogen-activated protein kinase kinase kinase 11 CHEMBL2708	IC50	5.94	5.94	1140.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	IC50	5.92	5.92	1215.0	1
Tyrosine-protein kinase Lck CHEMBL258	IC50	5.9	5.9	1250.0	1
Serine/threonine-protein kinase Nek4 CHEMBL5819	IC50	5.85	5.85	1402.0	1
Mitogen-activated protein kinase kinase kinase 9 CHEMBL2872	IC50	5.8	5.8	1578.0	1
Mitogen-activated protein kinase kinase kinase kinase 5 CHEMBL4852	IC50	5.8	5.8	1569.0	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	5.75	5.75	1756.0	1
Tyrosine-protein kinase receptor UFO CHEMBL4895	IC50	5.57	5.57	2705.0	1
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	5.53	5.53	2962.0	1
Tyrosine-protein kinase Yes CHEMBL2073	IC50	5.5	5.5	3195.0	1
Serine/threonine-protein kinase WNK2 CHEMBL5639	IC50	5.41	5.41	3892.0	1
Cytochrome P450 2C9 CHEMBL3397	IC50	5.35	5.35	4500.0	1
Cytochrome P450 2C19 CHEMBL3622	IC50	5.16	5.16	7000.0	1
Cytochrome P450 3A4 CHEMBL340	IC50	5.0	4.945	10000.0	2
Cytochrome P450 1A2 CHEMBL3356	IC50	4.68	4.68	21000.0	1
Cytochrome P450 2D6 CHEMBL289	IC50	4.64	4.64	23000.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	6575.8	ng.hr.mL-1	Rattus norvegicus
AUC	1602.1	ng.hr.mL-1	Rattus norvegicus
AUC	3848.5	ng.hr.mL-1	Canis lupus familiaris
AUC	3155.3	ng.hr.mL-1	Canis lupus familiaris
AUC	6017.1	ng.hr.mL-1	Mus musculus
AUC	839.1	ng.hr.mL-1	Mus musculus
CL	21.5	mL.min-1.kg-1	Rattus norvegicus
CL	21.5	mL.min-1.kg-1	Rattus norvegicus
CL	12.5	mL.min-1.kg-1	Canis lupus familiaris
CL	31.8	mL.min-1.kg-1	Mus musculus
CL	21.5	mL.min-1.kg-1	Rattus norvegicus
F	100.0	%	Rattus norvegicus
F	72.0	%	Canis lupus familiaris
F	62.0	%	Mus musculus
T1/2	2.5	hr	Rattus norvegicus
T1/2	10.6	hr	Canis lupus familiaris
T1/2	2.5	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Eukaryotic translation initiation factor 2-alpha kinase 3	IC50	=	0.4	nM	9.4	Inhibition of GST-tagged PERK cytoplasmic domain (536 to 1116) (unknown origin) ...	24900593
Eukaryotic translation initiation factor 2-alpha kinase 3	IC50	=	0.4	nM	9.4	Inhibition of GST tagged PERK cytoplasmic domain mediated EIF2alpha phosphorylat...	22827572
Unchecked	IC50	=	0.4	nM	9.4	Inhibition of Toxoplasma gondii GST-taggged IF2Kalpha in presence of ATP by ADP-...	34894691
L929	IC50	=	0.4	nM	9.4	Anti-neprotic activity in mouse L929 cells assessed as reduction in TNF-induced ...	31622096
Unchecked	IC50	=	0.4	nM	9.4	Anti-necroptic activity in TNF mediated cell death in mouse L929sAhFas cells pre...	36346971
MEF	IC50	=	7.3	nM	8.14	Anti-neprotic activity in mouse MEF cells assessed as reduction in TNF-induced n...	31622096
Unchecked	IC50	=	7.3	nM	8.14	Anti-necroptic activity in TNF mediated cell death in human MEF cells preincubat...	36346971
Receptor-interacting serine/threonine-protein kinase 1	IC50	=	18.0	nM	7.75	Inhibition of recombinant human GST-tagged RIPK1 (1 to 479 residues) incubated f...	31622096
Receptor-interacting serine/threonine-protein kinase 1	IC50	=	18.2	nM	7.74	Inhibition of GST tagged human recombinant RIPK1 incubated for 4 hrs by ADP-Glo ...	36346971
Mast/stem cell growth factor receptor Kit	IC50	=	154.0	nM	6.81	Inhibition of c-Kit	22827572
SARS-CoV-2	IC50	=	250.0	nM	6.6	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity o...	-
Aurora kinase B	IC50	=	407.0	nM	6.39	Inhibition of Aurora B	22827572
Protein-tyrosine kinase 6	IC50	=	412.0	nM	6.38	Inhibition of BRK	22827572
Eukaryotic translation initiation factor 2-alpha kinase 1	IC50	=	420.0	nM	6.38	Inhibition of HRI assessed as EIF2AK1 phosphorylation	22827572
Mitogen-activated protein kinase kinase kinase 10	IC50	=	452.0	nM	6.34	Inhibition of MLK2	22827572
Tyrosine-protein kinase Mer	IC50	=	474.0	nM	6.32	Inhibition of c-MER	22827572
Discoidin domain-containing receptor 2	IC50	=	524.0	nM	6.28	Inhibition of DDR2	22827572
Toxoplasma gondii	IC50	=	620.0	nM	6.21	Antiparasitic activity against Toxoplasma gondii RH tachyzoites infected in HFF ...	34894691
Interferon-induced, double-stranded RNA-activated protein kinase	IC50	=	696.0	nM	6.16	Inhibition of PKR assessed as EIF2AK2 phosphorylation	22827572
Myosin light chain kinase 2, skeletal/cardiac muscle	IC50	=	701.0	nM	6.15	Inhibition of MLCK2	22827572

Literature References

PubMed	DOI	Target Context	# Activities
22827572	10.1021/jm300713s	Mus musculus	8
22827572	10.1021/jm300713s	Rattus norvegicus	7
22827572	10.1021/jm300713s	Canis familiaris	6
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
22827572	10.1021/jm300713s	Eukaryotic translation initiation factor 2-alpha kinase 3	3
22827572	10.1021/jm300713s	BXPC-3	3
22827572	10.1021/jm300713s	Unchecked	3
24900593	10.1021/ml400228e	Cytochrome P450 3A4	2
24900593	10.1021/ml400228e	Eukaryotic translation initiation factor 2-alpha kinase 3	2
-	10.21203/rs.3.rs-23951/v1	SARS-CoV-2	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
36346971	10.1021/acs.jmedchem.2c01518	Unchecked	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
22827572	10.1021/jm300713s	Mitogen-activated protein kinase kinase kinase kinase 5	1
22827572	10.1021/jm300713s	Serine/threonine-protein kinase Nek4	1
22827572	10.1021/jm300713s	Mitogen-activated protein kinase kinase kinase 9	1
22827572	10.1021/jm300713s	High affinity nerve growth factor receptor	1
22827572	10.1021/jm300713s	NT-3 growth factor receptor	1
-	10.6019/CHEMBL5724564	Hepatocyte spheroids	1
22827572	10.1021/jm300713s	BDNF/NT-3 growth factors receptor	1

Data from ChEMBL 36 via Core Engine