Compound Detail

CHEMBL223360

LINIFANIB

🧪 Phase III

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🧪 Phase III

Cc1ccc(F)c(NC(=O)Nc2ccc(-c3cccc4[nH]nc(N)c34)cc2)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL223360
Name	LINIFANIB
Phase	Phase III
Structure Type	MOL
InChI Key	MPVGZUGXCQEXTM-UHFFFAOYSA-N

Known Names

A-741439 ABT-869 AL-39324 Linifanib RG-3635

148

Targets

336

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

375.4

MW (Da)

4.90

ALogP

HBA

HBD

95.8

PSA (Å²)

0.41

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

USAN Stem	-anib
USAN Year	2009

Extended Properties

Molecular Formula	C21H18FN5O
MW	375.41
Aromatic Rings	4
Heavy Atoms	28
NP-Likeness	-1.63

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Macrophage colony stimulating factor receptor inhibitor	INHIBITOR	Macrophage colony-stimulating factor 1 receptor	✓	✓
Tyrosine-protein kinase receptor FLT3 inhibitor	INHIBITOR	Receptor-type tyrosine-protein kinase FLT3	✓	✓
Platelet-derived growth factor receptor inhibitor	INHIBITOR	Platelet-derived growth factor receptor	✓	✓
Vascular endothelial growth factor receptor inhibitor	INHIBITOR	Vascular endothelial growth factor receptor	✓	✓

Indications

Carcinoma, Hepatocellular Breast Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Colonic Neoplasms Colorectal Neoplasms Macular Degeneration Rectal Neoplasms Endometriosis Neoplasms

Activity Summary

Kd 190 meas. best 9.2

IC50 79 meas. best 8.64

Ki 67 meas. best 9.0

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	9.2	8.3308	0.6	13
Cyclin-dependent kinase 8 CHEMBL5719	Ki	9.0	9.0	1.0	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	Kd	8.77	7.9707	1.7	15
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	8.72	7.75	1.9	3
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	8.64	8.0271	2.3	14
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	IC50	8.52	8.52	3.0	2
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	8.52	8.03	3.0	5
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	Kd	8.47	8.47	3.4	2
MV4-11 CHEMBL613835	IC50	8.47	7.315	3.4	2
Platelet-derived growth factor receptor beta CHEMBL1913	Ki	8.4	8.4	4.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	8.4	7.9814	4.0	7
Platelet-derived growth factor receptor alpha CHEMBL2007	Kd	8.38	8.38	4.2	2
UMP-CMP kinase CHEMBL5681	Kd	8.22	8.22	6.0	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	Kd	8.12	8.12	7.5	2
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	Ki	8.1	8.1	7.9	1
Platelet-derived growth factor receptor beta CHEMBL1913	IC50	8.1	7.42	8.0	4
Vascular endothelial growth factor receptor 2 CHEMBL279	Ki	8.1	8.1	7.9	1
Vascular endothelial growth factor receptor 2 CHEMBL279	Kd	8.09	8.09	8.1	2
Vascular endothelial growth factor receptor 3 CHEMBL1955	Ki	8.0	8.0	10.0	1
Muscle, skeletal receptor tyrosine-protein kinase CHEMBL5684	Kd	8.0	8.0	10.0	2
Vascular endothelial growth factor receptor 3 CHEMBL1955	IC50	7.9	7.1133	12.6	3
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	7.85	7.8167	14.0	3
Cyclin-dependent kinase 8 CHEMBL5719	IC50	7.85	6.72	14.0	4
Platelet-derived growth factor receptor alpha CHEMBL2007	IC50	7.82	7.82	15.0	1
Vascular endothelial growth factor receptor 3 CHEMBL1955	Kd	7.8	7.8	16.0	2
MOLM-13 CHEMBL3706572	IC50	7.72	7.72	19.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Ki	7.7	7.7	19.9	1
Cyclin-dependent kinase 19 CHEMBL6002	IC50	7.62	7.62	24.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Ki	7.6	7.6	25.1	1
NFS-60 CHEMBL614199	IC50	7.52	7.52	30.0	1
Ephrin type-B receptor 6 CHEMBL5836	Kd	7.48	7.48	33.0	1
Cyclin-dependent kinase 13 CHEMBL1795192	Kd	7.42	7.42	38.0	1
Homeodomain-interacting protein kinase 4 CHEMBL1075167	Ki	7.4	7.4	39.8	1
Homeodomain-interacting protein kinase 4 CHEMBL1075167	Kd	7.34	7.34	46.0	1
Platelet-derived growth factor receptor alpha CHEMBL2007	Ki	7.3	7.3	50.1	1
Ribosomal protein S6 kinase alpha-4 CHEMBL3125	Ki	7.3	7.3	50.1	1
Macrophage colony-stimulating factor 1 receptor CHEMBL5570	IC50	7.3	7.3	50.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	7.27	6.7086	54.0	7
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	7.24	7.24	58.0	2
Aurora kinase C CHEMBL3935	Kd	7.15	7.15	71.0	2
Cyclin-dependent kinase 19 CHEMBL6002	Kd	7.13	7.13	74.0	2
Aurora kinase B CHEMBL2185	Ki	7.1	7.1	79.4	1
Dual specificity protein kinase CLK4 CHEMBL4203	Ki	7.1	7.1	79.4	1
Protein smoothened CHEMBL5971	Ki	7.06	7.06	87.6	1
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	IC50	7.02	7.02	95.0	1
Cyclin-dependent kinase 8 CHEMBL5719	Kd	7.02	7.02	95.0	2
Ephrin type-A receptor 7 CHEMBL4602	Kd	6.96	6.96	110.0	1
Tyrosine-protein kinase receptor Tie-1 CHEMBL5274	Kd	6.96	6.96	110.0	2
Tyrosine-protein kinase receptor UFO CHEMBL4895	Ki	6.9	6.9	125.9	1
Angiopoietin-1 receptor CHEMBL4128	IC50	6.77	6.77	170.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	9197.55	ng.hr.mL-1	Mus musculus
AUC	6800.0	ng.hr.mL-1	Rattus norvegicus
AUC	600.0	ng.hr.mL-1	Macaca fascicularis
AUC	1500.0	ng.hr.mL-1	Canis lupus familiaris
AUC	7170.33	ng.hr.mL-1	Mus musculus
AUC	9197.55	ng.hr.mL-1	Mus musculus
CL	3.3	mL.min-1.kg-1	Rattus norvegicus
CL	8.2	mL.min-1.kg-1	Macaca fascicularis
CL	7.2	mL.min-1.kg-1	Canis lupus familiaris
CL	18.33	mL.min-1.kg-1	Mus musculus
F	100.0	%	Mus musculus
F	27.0	%	Rattus norvegicus
F	10.6	%	Macaca fascicularis
F	47.0	%	Canis lupus familiaris
T1/2	3.6	hr	Rattus norvegicus
T1/2	3.1	hr	Macaca fascicularis
T1/2	2.0	hr	Canis lupus familiaris
T1/2	1.7	hr	Mus musculus
Vd	2.7	L.kg-1	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Receptor-type tyrosine-protein kinase FLT3	Kd	=	0.63	nM	9.2	Binding constant for FLT3 kinase domain	22037378
Receptor-type tyrosine-protein kinase FLT3	Kd	=	0.63	nM	9.2	Binding constant for FLT3 kinase domain	18183025
Cyclin-dependent kinase 8	Ki	=	1.0	nM	9.0	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member na...	-
Receptor-type tyrosine-protein kinase FLT3	Kd	=	1.3	nM	8.89	Binding constant for FLT3(K663Q) kinase domain	22037378
Mast/stem cell growth factor receptor Kit	Kd	=	1.7	nM	8.77	Binding constant for KIT(V559D) kinase domain	22037378
Mast/stem cell growth factor receptor Kit	Kd	=	1.7	nM	8.77	Binding constant for KIT(V559D) kinase domain	18183025
Platelet-derived growth factor receptor beta	Kd	=	1.9	nM	8.72	Binding constant for PDGFRB kinase domain	22037378
Mast/stem cell growth factor receptor Kit	Kd	=	1.9	nM	8.72	Binding constant for KIT(L576P) kinase domain	22037378
Platelet-derived growth factor receptor beta	Kd	=	1.9	nM	8.72	Binding constant for PDGFRB kinase domain	18183025
Mast/stem cell growth factor receptor Kit	Kd	=	2.0	nM	8.7	Binding constant for KIT kinase domain	22037378
Mast/stem cell growth factor receptor Kit	Kd	=	2.0	nM	8.7	Binding affinity to human KIT incubated for 1 hr by kinase binding assay	21429632
Mast/stem cell growth factor receptor Kit	Kd	=	2.0	nM	8.7	Binding constant for KIT kinase domain	18183025
Vascular endothelial growth factor receptor 2	IC50	=	2.3	nM	8.64	Inhibition of VEGFR-2 in HUVEC assessed as inhibition of VEGF (1 to 165)-induced...	24900886
Receptor-type tyrosine-protein kinase FLT3	Kd	=	2.6	nM	8.59	Binding constant for FLT3(N841I) kinase domain	22037378
Receptor-type tyrosine-protein kinase FLT3	Kd	=	2.6	nM	8.59	Binding constant for FLT3(N841I) kinase domain	18183025
Receptor-type tyrosine-protein kinase FLT3	Kd	=	2.7	nM	8.57	Binding constant for FLT3(D835H) kinase domain	22037378
Receptor-type tyrosine-protein kinase FLT3	Kd	=	2.7	nM	8.57	Binding constant for FLT3(D835H) kinase domain	18183025
Vascular endothelial growth factor receptor 1	IC50	=	3.0	nM	8.52	Inhibition of FLT1 by HTRF assay	17343372
Vascular endothelial growth factor receptor 1	IC50	=	3.0	nM	8.52	Inhibition of FLT1 (unknown origin)	29266937
Macrophage colony-stimulating factor 1 receptor	IC50	=	3.0	nM	8.52	Inhibition of CSF1R by HTRF assay	17343372

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
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
26254279	10.18632/oncotarget.4214	Unchecked	8
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
18183025	10.1038/nbt1358	Tyrosine-protein kinase ABL1	7
28787156	10.1021/acs.jmedchem.7b00794	Protein smoothened	6
18183025	10.1038/nbt1358	Receptor-type tyrosine-protein kinase FLT3	6
18260617	10.1021/jm701096v	Mus musculus	6
18183025	10.1038/nbt1358	Mast/stem cell growth factor receptor Kit	5
29191878	10.1126/science.aan4368	Unchecked	5
35863236	10.1016/j.bmc.2022.116937	MV4-11	5
17343372	10.1021/jm061280h	Rattus norvegicus	5
17343372	10.1021/jm061280h	Cynomolgus monkey	5
17343372	10.1021/jm061280h	Canis familiaris	5
22037378	10.1038/nbt.1990	Proto-oncogene tyrosine-protein kinase receptor Ret	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
17343372	10.1021/jm061280h	Plasma	4

Data from ChEMBL 36 via Core Engine