Compound Detail

CHEMBL1822792

MK-2461

🧪 Phase II

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🧪 Phase II

CN(C[C@@H]1COCCO1)S(=O)(=O)Nc1ccc2ccc3ncc(-c4cnn(C)c4)cc3c(=O)c2c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1822792
Name	MK-2461
Phase	Phase II
Structure Type	MOL
InChI Key	JGEBLDKNWBUGRZ-HXUWFJFHSA-N

Known Names

Mk-2461

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

495.6

MW (Da)

2.15

ALogP

HBA

HBD

115.7

PSA (Å²)

0.44

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Extended Properties

Molecular Formula	C24H25N5O5S
MW	495.56
Aromatic Rings	4
Heavy Atoms	35
NP-Likeness	-1.44

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Hepatocyte growth factor receptor inhibitor	INHIBITOR	Hepatocyte growth factor receptor	✓	✓

Indications

Neoplasms Neoplasms

Activity Summary

IC50 35 meas. best 9.4

Kd 15 meas. best 8.4

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Hepatocyte growth factor receptor CHEMBL3717	IC50	9.4	8.0075	0.4	16
Hepatocyte growth factor receptor CHEMBL3717	Kd	8.4	7.9825	4.0	4
Macrophage-stimulating protein receptor CHEMBL2689	IC50	8.15	8.15	7.0	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	8.0	8.0	10.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	7.66	7.66	22.0	1
Tyrosine-protein kinase Mer CHEMBL5331	IC50	7.62	7.62	24.0	1
Fibroblast growth factor receptor 2 CHEMBL4142	IC50	7.41	7.41	39.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	7.36	7.36	44.0	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	7.34	7.34	46.0	1
Fibroblast growth factor receptor 3 CHEMBL2742	IC50	7.3	7.3	50.0	1
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	7.21	7.21	61.0	1
Fibroblast growth factor receptor 1 CHEMBL3650	IC50	7.19	7.19	65.0	1
Vascular endothelial growth factor receptor 3 CHEMBL1955	IC50	7.11	7.11	78.0	1
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	6.64	6.64	230.0	1
Macrophage-stimulating protein receptor CHEMBL2689	Kd	6.56	6.56	278.0	1
Aurora kinase A CHEMBL4722	IC50	6.54	6.54	290.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	6.36	6.36	440.0	1
Interleukin-1 receptor-associated kinase 3 CHEMBL5081	Kd	6.3	6.3	502.0	1
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	6.26	6.26	543.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	IC50	6.19	6.19	640.0	1
Mus musculus CHEMBL375	IC50	6.0	6.0	1000.0	1
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma CHEMBL1770034	Kd	5.99	5.99	1027.0	1
Cytochrome P450 2C9 CHEMBL3397	IC50	5.92	5.92	1200.0	1
Interleukin-1 receptor-associated kinase 4 CHEMBL3778	Kd	5.83	5.83	1475.0	1
Mitogen-activated protein kinase 9 CHEMBL4179	Kd	5.71	5.71	1931.0	1
Uncharacterized protein FLJ45252 CHEMBL4105933	Kd	5.59	5.59	2590.0	1
Ferrochelatase, mitochondrial CHEMBL3879831	Kd	5.47	5.47	3418.0	1
AP2-associated protein kinase 1 CHEMBL3830	Kd	5.44	5.44	3647.0	1
Mitogen-activated protein kinase 10 CHEMBL2637	Kd	5.33	5.33	4701.0	1
Cytochrome P450 3A4 CHEMBL340	IC50	5.15	5.15	7100.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	5.11	5.11	7800.0	1
Ribosyldihydronicotinamide dehydrogenase [quinone] CHEMBL3959	Kd	4.28	4.28	52632.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	6789.17	ng.hr.mL-1	Canis lupus familiaris
AUC	4162.7	ng.hr.mL-1	Canis lupus familiaris
AUC	5847.61	ng.hr.mL-1	Rattus norvegicus
AUC	3766.26	ng.hr.mL-1	Rattus norvegicus
AUC	297.34	ng.hr.mL-1	Mus musculus
AUC	198.22	ng.hr.mL-1	Mus musculus
AUC	495.56	ng.hr.mL-1	Macaca mulatta
AUC	198.22	ng.hr.mL-1	Macaca mulatta
CL	83.0	mL.min-1.kg-1	Mus musculus
CL	4.3	mL.min-1.kg-1	Canis lupus familiaris
CL	8.4	mL.min-1.kg-1	Macaca mulatta
CL	9.1	mL.min-1.kg-1	Rattus norvegicus
Cmax	410.0	nM	Mus musculus
Cmax	4200.0	nM	Rattus norvegicus
Cmax	2500.0	nM	Canis lupus familiaris
Cmax	120.0	nM	Macaca mulatta
F	62.0	%	Rattus norvegicus
F	75.0	%	Mus musculus
F	13.0	%	Canis lupus familiaris
F	14.0	%	Macaca mulatta
T1/2	0.5	hr	Mus musculus
T1/2	2.9	hr	Canis lupus familiaris
T1/2	0.8	hr	Macaca mulatta
T1/2	0.8	hr	Rattus norvegicus
Tmax	0.3	hr	Mus musculus
Tmax	0.7	hr	Rattus norvegicus
Tmax	1.4	hr	Canis lupus familiaris
Tmax	3.0	hr	Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Hepatocyte growth factor receptor	IC50	=	0.4	nM	9.4	Inhibition of c-Met (unknown origin)	26717201
Hepatocyte growth factor receptor	IC50	=	0.4	nM	9.4	Inhibition of recombinant human c-Met M1250T mutant-catalyzed phosphorylation of...	21608528
Hepatocyte growth factor receptor	IC50	=	0.5	nM	9.3	Inhibition of recombinant human c-Met Y1235D mutant-catalyzed phosphorylation of...	21608528
Hepatocyte growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of recombinant human c-Met Y1230H mutant-catalyzed phosphorylation of...	21608528
Hepatocyte growth factor receptor	IC50	=	1.5	nM	8.82	Inhibition of recombinant human c-Met N1100Y mutant-catalyzed phosphorylation of...	21608528
Hepatocyte growth factor receptor	IC50	=	1.5	nM	8.82	Inhibition of recombinant human c-Met Y1230C mutant-catalyzed phosphorylation of...	21608528
Hepatocyte growth factor receptor	IC50	=	2.0	nM	8.7	Inhibition of human recombinant c-Met-catalyzed phosphorylation of N-biotinylate...	21608528
Hepatocyte growth factor receptor	IC50	=	2.0	nM	8.7	Inhibition of human c-MET	21641696
Hepatocyte growth factor receptor	IC50	=	2.0	nM	8.7	Inhibition of c-MET (unknown origin)-catalyzed N-biotinylated EQEDEPEGDYFEWLECON...	23379595
Hepatocyte growth factor receptor	Kd	=	4.0	nM	8.4	Binding affinity to human recombinant His6-tagged phosphorylated c-Met cytosolic...	21608528
Hepatocyte growth factor receptor	Kd	=	4.4	nM	8.36	Binding affinity to human phosphorylated c-MET	21429632
Macrophage-stimulating protein receptor	IC50	=	7.0	nM	8.15	Inhibition of human Ron	21608528
Vascular endothelial growth factor receptor 1	IC50	=	10.0	nM	8.0	Inhibition of human Flt1	21608528
Receptor-type tyrosine-protein kinase FLT3	IC50	=	22.0	nM	7.66	Inhibition of human Flt3	21608528
Tyrosine-protein kinase Mer	IC50	=	24.0	nM	7.62	Inhibition of human Mer	21608528
Hepatocyte growth factor receptor	Kd	=	25.0	nM	7.6	Binding affinity to human recombinant His6-tagged unphosphorylated c-Met cytosol...	21608528
Hepatocyte growth factor receptor	IC50	=	26.0	nM	7.58	Inhibition of recombinant human c-MET phosphorylation at C-terminal Y1365	21608528
Hepatocyte growth factor receptor	Kd	=	27.2	nM	7.57	Binding affinity to human unphosphorylated c-MET	21429632
Fibroblast growth factor receptor 2	IC50	=	39.0	nM	7.41	Inhibition of human FGFR2	21608528
Vascular endothelial growth factor receptor 2	IC50	=	44.0	nM	7.36	Inhibition of human KDR	21608528

Literature References

PubMed	DOI	Target Context	# Activities
21608528	10.1021/jm200112k	Hepatocyte growth factor receptor	17
21608528	10.1021/jm200112k	Mus musculus	16
21608528	10.1021/jm200112k	Canis familiaris	8
21608528	10.1021/jm200112k	Rattus norvegicus	8
21608528	10.1021/jm200112k	Rhesus monkey	8
29191878	10.1126/science.aan4368	Unchecked	5
-	10.6019/CHEMBL4651402	SARS-CoV-2	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
21608528	10.1021/jm200112k	NON-PROTEIN TARGET	3
21608528	10.1021/jm200112k	No relevant target	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
21429632	10.1016/j.ejmech.2011.02.057	Hepatocyte growth factor receptor	2
21608528	10.1021/jm200112k	Platelet-derived growth factor receptor alpha	1
21608528	10.1021/jm200112k	Cytochrome P450 2C9	1
21608528	10.1021/jm200112k	Cytochrome P450 3A4	1
21608528	10.1021/jm200112k	Voltage-gated inwardly rectifying potassium channel KCNH2	1
21608528	10.1021/jm200112k	Unchecked	1
38157838	10.1016/j.bmc.2023.117561	Unchecked	1
21608528	10.1021/jm200112k	Tyrosine-protein kinase Mer	1

Data from ChEMBL 36 via Core Engine