Compound Detail

CHEMBL3137331

DEFACTINIB

🧪 Phase III

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🧪 Phase III

CNC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(NCc3nccnc3N(C)S(C)(=O)=O)n2)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3137331
Name	DEFACTINIB
Phase	Phase III
Structure Type	MOL
InChI Key	FWLMVFUGMHIOAA-UHFFFAOYSA-N

Known Names

Defactinib PF-04554878 Vs-6063

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

510.5

MW (Da)

2.40

ALogP

HBA

HBD

142.1

PSA (Å²)

0.42

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Flags

Chemical Probe

USAN Stem	-tinib
USAN Year	2013

Extended Properties

Molecular Formula	C20H21F3N8O3S
MW	510.50
Aromatic Rings	3
Heavy Atoms	35
NP-Likeness	-1.45

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Focal adhesion kinase 1 inhibitor	INHIBITOR	Focal adhesion kinase 1	✓	✓
Protein tyrosine kinase 2 beta inhibitor	INHIBITOR	Protein-tyrosine kinase 2-beta	✓	✓

Indications

Ovarian Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Pancreatic Ductal Colorectal Neoplasms Genital Neoplasms, Female Lung Neoplasms Mesothelioma Pancreatic Neoplasms Thyroid Neoplasms Carcinoma, Endometrioid Melanoma Neoplasms Glioblastoma

Activity Summary

IC50 49 meas. best 9.7

Kd 41 meas. best 9.3

Ki 7 meas. best 9.0

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Protein-tyrosine kinase 2-beta CHEMBL5469	IC50	9.7	8.82	0.2	3
Focal adhesion kinase 1 CHEMBL2695	IC50	9.7	8.9508	0.2	12
Focal adhesion kinase 1 CHEMBL2695	Kd	9.3	9.3	0.5	1
Unchecked CHEMBL612545	IC50	9.22	9.22	0.6	1
Focal adhesion kinase 1 CHEMBL2695	Ki	9.0	9.0	1.0	1
Unchecked CHEMBL612545	Kd	8.72	6.8367	1.9	3
Cyclin-dependent kinase-like 5 CHEMBL1163112	Kd	7.8	7.8	16.0	1
Protein-tyrosine kinase 2-beta CHEMBL5469	Kd	7.62	6.995	24.0	2
High affinity nerve growth factor receptor CHEMBL2815	IC50	7.58	7.36	26.6	3
Adenosine receptor A3 CHEMBL256	Ki	7.57	7.57	27.0	2
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	7.55	7.55	28.2	1
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	7.26	7.26	54.9	1
NT-3 growth factor receptor CHEMBL5608	IC50	7.24	7.24	57.8	1
Mitogen-activated protein kinase kinase kinase 9 CHEMBL2872	IC50	7.12	7.12	75.3	2
Tyrosine-protein kinase JAK3 CHEMBL2148	IC50	6.94	6.94	114.9	1
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	IC50	6.89	6.89	129.0	1
Aurora kinase A CHEMBL4722	IC50	6.87	6.87	135.0	1
Dual specificity protein kinase CLK1 CHEMBL4224	IC50	6.6	6.6	250.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	6.56	6.56	273.2	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.47	6.47	340.0	1
Cyclin-dependent kinase 2/cyclin A CHEMBL2094128	IC50	6.46	6.46	344.0	1
Adenosine receptor A2a CHEMBL251	Ki	6.43	6.43	370.0	1
Glycogen synthase kinase-3 beta CHEMBL262	IC50	6.38	6.38	416.0	1
Serine/threonine-protein kinase MARK1 CHEMBL5940	IC50	6.35	6.35	448.0	1
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	6.34	6.34	454.0	1
Aurora kinase A CHEMBL4722	Kd	6.21	6.21	622.0	1
Protein-tyrosine kinase 2-beta CHEMBL5469	Ki	6.2	6.2	630.0	1
Cyclin-dependent kinase 12 CHEMBL3559692	Kd	6.14	6.14	730.0	1
Maternal embryonic leucine zipper kinase CHEMBL4578	Kd	6.05	6.05	897.0	1
Serine/threonine-protein kinase 16 CHEMBL3938	Kd	6.05	6.05	893.0	1
Mitogen-activated protein kinase kinase kinase 11 CHEMBL2708	Kd	6.04	6.04	902.0	1
High affinity nerve growth factor receptor CHEMBL2815	Kd	6.04	6.04	918.0	1
Tyrosine-protein kinase Lyn CHEMBL3905	IC50	5.96	5.96	1100.0	1
Casein kinase II subunit alpha' CHEMBL4070	Kd	5.92	5.92	1201.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Kd	5.88	5.88	1303.0	1
Glycogen synthase kinase-3 beta CHEMBL262	Kd	5.88	5.88	1322.0	1
Cyclin-dependent kinase 5 CHEMBL4036	Kd	5.85	5.85	1414.0	1
Aurora kinase B CHEMBL2185	Kd	5.83	5.83	1464.0	1
Glycogen synthase kinase-3 alpha CHEMBL2850	Kd	5.83	5.83	1462.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	5.79	5.79	1640.0	1
Cyclin-dependent kinase 2 CHEMBL301	Kd	5.78	5.78	1656.0	1
Cyclin-dependent kinase 7 CHEMBL3055	Kd	5.76	5.76	1744.0	1
Cyclin-dependent kinase 9 CHEMBL3116	Kd	5.75	5.75	1790.0	1
Cyclin-dependent kinase 1 CHEMBL308	Kd	5.7	5.7	2014.0	1
General transcription and DNA repair factor IIH helicase subunit XPD CHEMBL4105743	Kd	5.65	5.65	2259.0	1
Serine/threonine-protein kinase 4 CHEMBL4598	Kd	5.61	5.61	2450.0	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	5.6	5.6	2500.0	1
HCT-116 CHEMBL394	IC50	5.58	5.58	2650.0	1
Serine/threonine-protein kinase MARK2 CHEMBL3831	Kd	5.58	5.58	2601.0	1
Wee1-like protein kinase CHEMBL5491	Kd	5.58	5.58	2604.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
T1/2	0.09	hr	Homo sapiens
T1/2	0.02167	hr	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Protein-tyrosine kinase 2-beta	IC50	=	0.2	nM	9.7	Binding assay (PTK2B)	-
Focal adhesion kinase 1	IC50	=	0.2	nM	9.7	Affinity Biochemical interaction (Binding assay) EUB0000138c PTK2	-
Protein-tyrosine kinase 2-beta	IC50	=	0.2	nM	9.7	Affinity Biochemical interaction (Binding assay) EUB0000138c PTK2B	-
Focal adhesion kinase 1	IC50	=	0.2	nM	9.7	Binding assay (PTK2)	-
Focal adhesion kinase 1	Kd	=	0.5	nM	9.3	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Focal adhesion kinase 1	IC50	=	0.6	nM	9.22	Inhibition of human recombinant FAK	31129452
Unchecked	IC50	=	0.6	nM	9.22	Inhibition of FAK (unknown origin)	32784087
Focal adhesion kinase 1	IC50	=	0.6	nM	9.22	Inhibition of FAK (unknown origin)	37974962
Focal adhesion kinase 1	IC50	=	0.63	nM	9.2	Inhibition of FAK (unknown origin) using Fluorescein-Poly GAT as substrate incub...	34810020
Focal adhesion kinase 1	Ki	=	1.0	nM	9.0	Inhibition of full-length FAK (unknown origin) with N-terminal NanoLuc-fusion ex...	33497606
Focal adhesion kinase 1	IC50	=	1.16	nM	8.94	Inhibition of FAK (unknown origin) incubated for 40 mins by HTRF assay	34091209
Focal adhesion kinase 1	IC50	=	1.5	nM	8.82	Inhibition of GST-FAK catalytic domain region (411-686) (unknown origin) express...	33488961
Focal adhesion kinase 1	IC50	=	1.79	nM	8.75	In Vitro Activity Assay: The in vitro activity of the compounds of the compounds...	-
Unchecked	Kd	=	1.9	nM	8.72	Binding affinity to human recombinant FAK P410G mutant (amino acids 410-689) exp...	33497606
Focal adhesion kinase 1	IC50	=	3.0	nM	8.52	Inhibition of human PTK2 phosphorylation in A431 cells	-
Focal adhesion kinase 1	IC50	=	3.0	nM	8.52	Affinity On-target Cellular interaction (Inhibition of human PTK2 phosphorylatio...	-
Focal adhesion kinase 1	IC50	=	3.9	nM	8.41	Inhibition of FAK (unknown origin)	36306471
Focal adhesion kinase 1	IC50	=	3.9	nM	8.41	Inhibition of human recombinant FAK using poly[Glu:Tyr] (4:1) substrate in prese...	32292541
Cyclin-dependent kinase-like 5	Kd	=	16.0	nM	7.8	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Protein-tyrosine kinase 2-beta	Kd	=	24.0	nM	7.62	Binding affinity to human recombinant PYK2 (amino acids 420-691) expressed in Es...	33497606

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	U2OS	523
-	10.6019/CHEMBL4689842	Fibroblast	522
-	10.6019/CHEMBL4689842	HEK-293T	521
33497606	10.1016/j.chembiol.2021.01.003	Unchecked	27
-	10.6019/CHEMBL4507299	Tyrosine-protein kinase ABL1	17
-	10.6019/CHEMBL5724696	U2OS	16
-	10.6019/CHEMBL4507299	Epidermal growth factor receptor	13
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL4507299	Receptor-type tyrosine-protein kinase FLT3	11
-	10.6019/CHEMBL4507299	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
-	10.6019/CHEMBL4507299	Mast/stem cell growth factor receptor Kit	9
34091209	10.1016/j.ejmech.2021.113573	Unchecked	7
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
33497606	10.1016/j.chembiol.2021.01.003	Protein-tyrosine kinase 2-beta	6
33488961	10.1021/acsmedchemlett.0c00338	Focal adhesion kinase 1	6
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
-	10.6019/CHEMBL5212743	Receptor-type tyrosine-protein kinase FLT3	5
-	10.6019/CHEMBL4507299	Hepatocyte growth factor receptor	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4

Data from ChEMBL 36 via Core Engine