Compound Detail

CHEMBL2029988

CEP-32496

🧪 Phase II

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🧪 Phase II

COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C(F)(F)F)on4)c3)c2cc1OC

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL2029988
Name	CEP-32496
Phase	Phase II
Structure Type	MOL
InChI Key	DKNUPRMJNUQNHR-UHFFFAOYSA-N

Known Names

AB-024 AC-013773 Agerafenib Cep-32496 Rxdx 105 RXDX-105

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

517.5

MW (Da)

5.91

ALogP

HBA

HBD

120.6

PSA (Å²)

0.31

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Extended Properties

Molecular Formula	C24H22F3N5O5
MW	517.46
Aromatic Rings	4
Heavy Atoms	37
NP-Likeness	-1.37

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase B-raf inhibitor	INHIBITOR	Serine/threonine-protein kinase B-raf	✓	✓
Epidermal growth factor receptor erbB1 inhibitor	INHIBITOR	Epidermal growth factor receptor	✓	✓
Tyrosine-protein kinase receptor RET inhibitor	INHIBITOR	Proto-oncogene tyrosine-protein kinase receptor Ret	✓	✓

Indications

Neoplasms

Activity Summary

Kd 51 meas. best 8.82

IC50 21 meas. best 9.48

EC50 9 meas. best 7.44

Ki 1 meas. best 6.73

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET CHEMBL3430904	IC50	9.48	8.815	0.3	2
Proto-oncogene tyrosine-protein kinase receptor Ret /Nuclear receptor coactivator 4 fusion protein CHEMBL3430877	IC50	9.39	9.39	0.4	1
Unchecked CHEMBL612545	IC50	9.09	7.915	0.8	4
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	8.82	8.4933	1.5	3
Mast/stem cell growth factor receptor Kit CHEMBL1936	Kd	8.7	8.66	2.0	2
Tyrosine-protein kinase Lck CHEMBL258	Kd	8.7	8.7	2.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	IC50	8.7	7.7714	2.0	7
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	8.7	8.7	2.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	8.55	8.1233	2.8	3
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	8.22	8.22	6.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	Kd	8.1	8.1	7.9	2
Macrophage colony-stimulating factor 1 receptor CHEMBL1844	Kd	8.05	8.05	9.0	1
Serine/threonine-protein kinase B-raf CHEMBL5145	Kd	7.85	7.0917	14.0	6
Vascular endothelial growth factor receptor 1 CHEMBL1868	Kd	7.85	7.85	14.0	1
Ephrin type-A receptor 2 CHEMBL2068	Kd	7.85	7.345	14.0	2
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	7.77	7.57	17.0	2
Epidermal growth factor receptor CHEMBL203	Kd	7.66	7.66	22.0	1
Tyrosine-protein kinase ABL2 CHEMBL4014	Kd	7.52	7.52	30.0	1
COLO 205 CHEMBL614561	EC50	7.44	7.44	36.0	1
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	Kd	7.41	7.41	39.0	2
Breakpoint cluster region protein CHEMBL5146	Kd	7.39	7.39	41.0	1
A-375 CHEMBL613859	IC50	7.11	7.11	78.0	1
Serine/threonine-protein kinase B-raf CHEMBL5145	IC50	7.09	7.09	82.0	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	6.91	6.91	124.0	1
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	IC50	6.84	6.84	146.0	1
Mitogen-activated protein kinase 9 CHEMBL4179	Kd	6.83	6.83	148.0	1
Discoidin domain-containing receptor 2 CHEMBL5122	Kd	6.74	6.74	183.0	1
Protein smoothened CHEMBL5971	Ki	6.73	6.73	187.8	1
COLO-679 CHEMBL1075426	EC50	6.68	6.68	211.0	1
HT-144 CHEMBL2366291	EC50	6.64	6.64	228.0	1
Receptor-interacting serine/threonine-protein kinase 3 CHEMBL1795199	Kd	6.61	6.61	245.0	1
Mitogen-activated protein kinase 10 CHEMBL2637	Kd	6.42	6.42	378.0	1
Ephrin type-A receptor 5 CHEMBL3987	Kd	6.4	6.4	401.0	1
Receptor-interacting serine/threonine-protein kinase 2 CHEMBL5014	Kd	6.36	6.36	442.0	1
SK-MEL-28 CHEMBL614919	EC50	6.34	6.34	454.0	1
MAP kinase-activated protein kinase 2 CHEMBL2208	Kd	6.31	6.31	490.0	1
Hepatocyte growth factor receptor CHEMBL3717	Kd	6.29	6.29	513.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.26	6.26	550.0	1
Mitogen-activated protein kinase 14 CHEMBL260	Kd	6.25	6.25	566.0	1
HCT-116 CHEMBL394	EC50	6.17	6.17	669.0	1
Tyrosine-protein kinase Lyn CHEMBL3905	Kd	6.11	6.11	771.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Kd	6.07	6.07	850.0	1
Mitogen-activated protein kinase 11 CHEMBL3961	Kd	6.06	6.06	872.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Kd	6.01	6.01	980.0	1
Mitogen-activated protein kinase kinase kinase 20 CHEMBL3886	Kd	6.0	6.0	998.0	1
Mitogen-activated protein kinase 8 CHEMBL2276	Kd	5.83	5.83	1471.0	1
Myosin light chain kinase, smooth muscle CHEMBL2428	Kd	5.57	5.57	2683.0	1
Hs-578T CHEMBL614645	EC50	5.56	5.56	2736.0	1
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	Kd	5.55	5.55	2822.0	1
DU-145 CHEMBL613508	EC50	5.54	5.54	2911.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	47709.81	ng.hr.mL-1	Macaca fascicularis
AUC	28512.05	ng.hr.mL-1	Canis lupus familiaris
AUC	203879.24	ng.hr.mL-1	Mus musculus
AUC	38499.02	ng.hr.mL-1	Rattus norvegicus
CL	23000.0	mL.min-1.g-1	Macaca fascicularis
CL	23000.0	mL.min-1.g-1	Homo sapiens
CL	23000.0	mL.min-1.g-1	Canis lupus familiaris
CL	23000.0	mL.min-1.g-1	Mus musculus
CL	6.7	mL.min-1.kg-1	Macaca fascicularis
CL	5.0	mL.min-1.kg-1	Canis lupus familiaris
CL	3.4	mL.min-1.kg-1	Rattus norvegicus
Cmax	4300.0	nM	Macaca fascicularis
Cmax	5200.0	nM	Canis lupus familiaris
Cmax	35600.0	nM	Mus musculus
Cmax	6500.0	nM	Rattus norvegicus
F	100.0	%	Macaca fascicularis
F	100.0	%	Canis lupus familiaris
F	94.0	%	Rattus norvegicus
T1/2	7.8	hr	Rattus norvegicus
T1/2	12.0	hr	Canis lupus familiaris
T1/2	4.9	hr	Macaca fascicularis
T1/2	1.0	hr	Mus musculus
T1/2	1.0	hr	Canis lupus familiaris
T1/2	1.0	hr	Homo sapiens
T1/2	1.0	hr	Macaca fascicularis
Tmax	2.0	hr	Rattus norvegicus
Tmax	1.3	hr	Mus musculus
Tmax	2.0	hr	Canis lupus familiaris
Tmax	4.0	hr	Macaca fascicularis
Vd	1.6	L.kg-1	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET	IC50	=	0.33	nM	9.48	Inhibition of CCDC6-RET (unknown origin)	34402300
Proto-oncogene tyrosine-protein kinase receptor Ret /Nuclear receptor coactivator 4 fusion protein	IC50	=	0.41	nM	9.39	Inhibition of NCOA4-RET (unknown origin)	34402300
Unchecked	IC50	=	0.81	nM	9.09	Inhibition of PRKA1A-RET (unknown origin)	34402300
Unchecked	IC50	=	1.0	nM	9.0	Inhibition of C-KIT (unknown origin) by kinomescan assay	34402300
Proto-oncogene tyrosine-protein kinase receptor Ret	Kd	=	1.5	nM	8.82	Binding affinity to RET (unknown origin) assessed as dissociation constant measu...	34402300
Proto-oncogene tyrosine-protein kinase receptor Ret	Kd	=	2.0	nM	8.7	Inhibition of Ret in human HEK293 cells after 1 hr by competition binding assay	22168626
Platelet-derived growth factor receptor beta	Kd	=	2.0	nM	8.7	Inhibition of PDGFRbeta in human HEK293 cells after 1 hr by competition binding ...	22168626
Tyrosine-protein kinase Lck	Kd	=	2.0	nM	8.7	Inhibition of LCK in human HEK293 cells after 1 hr by competition binding assay	22168626
Mast/stem cell growth factor receptor Kit	Kd	=	2.0	nM	8.7	Inhibition of cKit in human HEK293 cells after 1 hr by competition binding assay	22168626
Proto-oncogene tyrosine-protein kinase receptor Ret	IC50	=	2.0	nM	8.7	Inhibition of human RET kinase using IGF1Rtide as substrate incubated for 40 min...	35305461
Mast/stem cell growth factor receptor Kit	Kd	=	2.4	nM	8.62	Binding affinity to C-KIT (unknown origin) assessed as dissociation constant mea...	34402300
Tyrosine-protein kinase ABL1	Kd	=	2.8	nM	8.55	Binding affinity to ABL (unknown origin) assessed as dissociation constant measu...	34402300
Tyrosine-protein kinase ABL1	Kd	=	3.0	nM	8.52	Inhibition of Abl1 in human HEK293 cells after 1 hr by competition binding assay	22168626
Proto-oncogene tyrosine-protein kinase receptor Ret	IC50	=	4.0	nM	8.4	Inhibition of recombinant RET M918T (unknown origin) incubated for 120 mins by P...	34402300
Proto-oncogene tyrosine-protein kinase receptor Ret	IC50	=	4.34	nM	8.36	Inhibition of RET M918T (unknown origin)	34402300
Tyrosine-protein kinase ABL1	IC50	=	6.0	nM	8.22	Inhibition of ABL (unknown origin) by kinomescan assay	34402300
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET	IC50	=	7.0	nM	8.15	Inhibition of recombinant CCDC6-RET (unknown origin) incubated for 120 mins by P...	34402300
Proto-oncogene tyrosine-protein kinase receptor Ret	IC50	=	7.0	nM	8.15	Inhibition of RET (unknown origin) by kinomescan assay	34402300
Vascular endothelial growth factor receptor 2	Kd	=	8.0	nM	8.1	Inhibition of VEGFR2 in human HEK293 cells after 1 hr by competition binding ass...	22168626
Vascular endothelial growth factor receptor 2	Kd	=	7.9	nM	8.1	Binding affinity to VEGFR2 (unknown origin) assessed as dissociation constant me...	34402300

Literature References

PubMed	DOI	Target Context	# Activities
22168626	10.1021/jm2009925	Mus musculus	14
22168626	10.1021/jm2009925	Canis familiaris	7
22168626	10.1021/jm2009925	Cynomolgus monkey	7
22168626	10.1021/jm2009925	Rattus norvegicus	7
34402300	10.1021/acs.jmedchem.0c02167	Proto-oncogene tyrosine-protein kinase receptor Ret	7
28787156	10.1021/acs.jmedchem.7b00794	Protein smoothened	6
22168626	10.1021/jm2009925	COLO 205	5
29191878	10.1126/science.aan4368	Unchecked	5
34402300	10.1021/acs.jmedchem.0c02167	Unchecked	5
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
22168626	10.1021/jm2009925	Liver	4
22168626	10.1021/jm2009925	Serine/threonine-protein kinase B-raf	3
34402300	10.1021/acs.jmedchem.0c02167	Vascular endothelial growth factor receptor 2	3
22168626	10.1021/jm2009925	Liver microsomes	3
34402300	10.1021/acs.jmedchem.0c02167	K562	2
22168626	10.1021/jm2009925	ADMET	2
34402300	10.1021/acs.jmedchem.0c02167	Serine/threonine-protein kinase B-raf	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
34402300	10.1021/acs.jmedchem.0c02167	HUVEC	2

Data from ChEMBL 36 via Core Engine