Compound Detail

CHEMBL558752

RAF-265

🧪 Phase II

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🧪 Phase II

Cn1c(Nc2ccc(C(F)(F)F)cc2)nc2cc(Oc3ccnc(-c4ncc(C(F)(F)F)[nH]4)c3)ccc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL558752
Name	RAF-265
Phase	Phase II
Structure Type	MOL
InChI Key	YABJJWZLRMPFSI-UHFFFAOYSA-N

Known Names

CHIR-265 NVP-RAF265 Raf 265 Raf-265 RAF265

Targets

175

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

518.4

MW (Da)

6.93

ALogP

HBA

HBD

80.7

PSA (Å²)

0.25

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Extended Properties

Molecular Formula	C24H16F6N6O
MW	518.42
Aromatic Rings	5
Heavy Atoms	37
NP-Likeness	-1.11

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase B-raf inhibitor	INHIBITOR	Serine/threonine-protein kinase B-raf	✓	✓
Vascular endothelial growth factor receptor 2 inhibitor	INHIBITOR	Vascular endothelial growth factor receptor 2	✓	✓

Indications

Melanoma Neoplasms

Activity Summary

Kd 147 meas. best 7.89

IC50 28 meas. best 9.3

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Serine/threonine-protein kinase B-raf CHEMBL5145	IC50	9.3	7.6014	0.5	7
Platelet-derived growth factor receptor beta CHEMBL1913	IC50	8.22	8.22	6.0	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	7.89	7.89	13.0	2
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	IC50	7.72	6.82	19.0	2
Vascular endothelial growth factor receptor CHEMBL2095227	IC50	7.7	7.7	20.0	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	7.7	7.7	20.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.4	7.125	40.0	2
Malme-3M CHEMBL614021	IC50	7.4	7.125	40.0	2
A-375 CHEMBL613859	IC50	7.4	7.4	40.0	1
Ephrin type-B receptor 6 CHEMBL5836	Kd	7.37	7.37	43.0	1
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	7.27	7.27	54.0	1
eIF-2-alpha kinase GCN2 CHEMBL5358	Kd	7.26	7.26	55.0	2
Serine/threonine-protein kinase 10 CHEMBL3981	Kd	7.22	7.22	60.0	2
Mitogen-activated protein kinase kinase kinase 20 CHEMBL3886	Kd	7.2	7.2	63.0	2
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	7.14	6.9117	72.0	6
Mast/stem cell growth factor receptor Kit CHEMBL1936	Kd	7.08	6.186	83.0	15
Citron Rho-interacting kinase CHEMBL5579	Kd	7.06	7.06	87.0	2
SK-MEL-28 CHEMBL614919	IC50	6.85	6.825	140.0	2
Serine/threonine-protein kinase TAO2 CHEMBL1075195	Kd	6.85	6.235	140.0	2
Tyrosine-protein kinase receptor Tie-1 CHEMBL5274	Kd	6.82	6.82	150.0	2
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	6.68	5.8644	210.0	18
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	6.62	6.62	240.0	2
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	Kd	6.6	6.6	250.0	2
Serine/threonine-protein kinase B-raf CHEMBL5145	Kd	6.48	6.2	330.0	4
Tyrosine-protein kinase Lyn CHEMBL3905	Kd	6.43	6.43	370.0	2
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	Kd	6.41	6.41	390.0	2
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	Kd	6.39	6.39	410.0	1
Mitogen-activated protein kinase kinase kinase 7 CHEMBL5776	Kd	6.31	6.31	490.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	6.29	6.29	510.0	2
Homeodomain-interacting protein kinase 4 CHEMBL1075167	Kd	6.25	6.25	560.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Kd	6.23	6.23	590.0	2
Tyrosine-protein kinase Lck CHEMBL258	Kd	6.19	6.19	640.0	2
Serine/threonine-protein kinase TAO3 CHEMBL5701	Kd	6.14	6.14	720.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.14	5.9467	730.0	3
Serine/threonine-protein kinase PAK 3 CHEMBL2999	Kd	6.11	6.11	770.0	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	Kd	6.1	6.1	800.0	2
Mitogen-activated protein kinase kinase kinase kinase 5 CHEMBL4852	Kd	6.08	6.08	830.0	2
Tyrosine-protein kinase Yes CHEMBL2073	Kd	6.03	6.03	940.0	2
Interferon-induced, double-stranded RNA-activated protein kinase CHEMBL5785	Kd	6.02	6.02	950.0	2
Discoidin domain-containing receptor 2 CHEMBL5122	Kd	6.02	6.02	960.0	2
Receptor-interacting serine/threonine-protein kinase 2 CHEMBL5014	Kd	6.02	6.02	950.0	2
Ephrin type-A receptor 8 CHEMBL4134	Kd	5.96	5.96	1100.0	2
Platelet-derived growth factor receptor alpha CHEMBL2007	Kd	5.96	5.96	1100.0	2
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	Kd	5.96	5.96	1100.0	2
Tyrosine-protein kinase HCK CHEMBL3234	Kd	5.92	5.92	1200.0	2
Angiopoietin-1 receptor CHEMBL4128	Kd	5.89	5.89	1300.0	2
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	5.89	5.89	1300.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	Kd	5.89	5.89	1300.0	2
Mitogen-activated protein kinase kinase kinase kinase 4 CHEMBL6166	Kd	5.89	5.89	1300.0	2
Hepatocyte growth factor receptor CHEMBL3717	Kd	5.85	5.53	1400.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	233289.0	ng.hr.mL-1	Rattus norvegicus
AUC	2229206.0	ng.hr.mL-1	Mus musculus
AUC	18144.7	ng.hr.mL-1	Canis lupus familiaris
AUC	24884.16	ng.hr.mL-1	Macaca mulatta
CL	0.8	mL.min-1.kg-1	Canis lupus familiaris
CL	0.9	mL.min-1.kg-1	Rattus norvegicus
CL	0.1	mL.min-1.kg-1	Mus musculus
CL	1.5	mL.min-1.kg-1	Macaca mulatta
F	35.0	%	Canis lupus familiaris
F	95.0	%	Rattus norvegicus
F	51.0	%	Mus musculus
F	48.0	%	Macaca mulatta
T1/2	46.0	hr	Rattus norvegicus
T1/2	41.0	hr	Mus musculus
T1/2	28.0	hr	Macaca mulatta
T1/2	27.0	hr	Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Serine/threonine-protein kinase B-raf	IC50	=	0.5	nM	9.3	Inhibition of B-RAF V600E mutant (unknown origin)	26396681
Platelet-derived growth factor receptor beta	IC50	=	6.0	nM	8.22	Inhibition of PDGFRbeta (unknown origin)	26396681
Epithelial discoidin domain-containing receptor 1	Kd	=	13.0	nM	7.89	Binding constant for DDR1 kinase domain	18183025
Epithelial discoidin domain-containing receptor 1	Kd	=	13.0	nM	7.89	Binding constant for DDR1 kinase domain	22037378
RAF proto-oncogene serine/threonine-protein kinase	IC50	=	19.0	nM	7.72	Inhibition of wild type c-RAF (unknown origin)	26396681
Serine/threonine-protein kinase B-raf	IC50	=	20.0	nM	7.7	Inhibition of recombinant human GST-tagged BRAF V600E mutant expressed in baculo...	30613326
Mast/stem cell growth factor receptor Kit	IC50	=	20.0	nM	7.7	Inhibition of c-KIT (unknown origin)	26396681
Vascular endothelial growth factor receptor	IC50	=	20.0	nM	7.7	Inhibition of VEGFR (unknown origin)	26396681
Serine/threonine-protein kinase B-raf	IC50	=	40.0	nM	7.4	Inhibition of B-RAF V600E mutant in human WM-1799 cells assessed as phosphorylat...	26396681
NON-PROTEIN TARGET	IC50	=	40.0	nM	7.4	Antiproliferative activity against human WM1799 cells harboring B-RAF V600E muta...	26396681
Malme-3M	IC50	=	40.0	nM	7.4	Antiproliferative activity against human MALME-3M cells harboring B-RAF V600E mu...	26396681
Serine/threonine-protein kinase B-raf	IC50	=	40.0	nM	7.4	Inhibition of B-RAF V600E mutant in human Malme-3M cells assessed as phosphoryla...	26396681
A-375	IC50	=	40.0	nM	7.4	Antiproliferative activity against human A375 cells harboring B-RAF V600E mutant	26396681
Serine/threonine-protein kinase B-raf	IC50	=	40.0	nM	7.4	Inhibition of B-RAF V600E mutant in human A375 cells assessed as phosphorylation...	26396681
Ephrin type-B receptor 6	Kd	=	43.0	nM	7.37	Binding constant for EPHB6 kinase domain	22037378
Mitogen-activated protein kinase kinase kinase 19	Kd	=	54.0	nM	7.27	Binding constant for YSK4 kinase domain	22037378
eIF-2-alpha kinase GCN2	Kd	=	55.0	nM	7.26	Binding constant for GCN2(Kin.Dom.2,S808G) kinase domain	18183025
eIF-2-alpha kinase GCN2	Kd	=	55.0	nM	7.26	Binding constant for GCN2(Kin.Dom.2,S808G) kinase domain	22037378
Serine/threonine-protein kinase 10	Kd	=	60.0	nM	7.22	Binding constant for LOK kinase domain	18183025
Serine/threonine-protein kinase 10	Kd	=	60.0	nM	7.22	Binding constant for LOK kinase domain	22037378

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
26396681	10.1021/ml500526p	Mus musculus	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
26254279	10.18632/oncotarget.4214	Unchecked	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
18183025	10.1038/nbt1358	Tyrosine-protein kinase ABL1	7
26396681	10.1021/ml500526p	Serine/threonine-protein kinase B-raf	6
-	10.6019/CHEMBL4495565	SARS-CoV-2	6
18183025	10.1038/nbt1358	Mast/stem cell growth factor receptor Kit	5
18183025	10.1038/nbt1358	Receptor-type tyrosine-protein kinase FLT3	5
26396681	10.1021/ml500526p	Rhesus monkey	5
29191878	10.1126/science.aan4368	Unchecked	5
26396681	10.1021/ml500526p	Rattus norvegicus	5
26396681	10.1021/ml500526p	Canis familiaris	5
26396681	10.1021/ml500526p	Plasma	4
22037378	10.1038/nbt.1990	Proto-oncogene tyrosine-protein kinase receptor Ret	4
22037378	10.1038/nbt.1990	Hepatocyte growth factor receptor	3

Data from ChEMBL 36 via Core Engine