Compound Detail

CHEMBL180022

NERATINIB

💊 Approved Drug

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💊 Approved Drug

CCOc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL180022
Name	NERATINIB
Phase	Approved
Structure Type	MOL
InChI Key	JWNPDZNEKVCWMY-VQHVLOKHSA-N
Therapeutic	✓ Yes

Known Names

CDP-820 HKI-272 Neratinib WAY-179272

128

Targets

253

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

557.0

MW (Da)

5.93

ALogP

HBA

HBD

112.4

PSA (Å²)

0.22

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2017
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Natural Product

USAN Stem	-tinib
USAN Year	2006

Extended Properties

Molecular Formula	C30H29ClN6O3
MW	557.05
Aromatic Rings	4
Heavy Atoms	40
NP-Likeness	-1.65

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Epidermal growth factor receptor erbB1 inhibitor	INHIBITOR	Epidermal growth factor receptor	✓	✓
Receptor protein-tyrosine kinase erbB-2 inhibitor	INHIBITOR	Receptor tyrosine-protein kinase erbB-2	✓	✓
Receptor protein-tyrosine kinase erbB-4 inhibitor	INHIBITOR	Receptor tyrosine-protein kinase erbB-4	✓	✓

Indications

Biliary Tract Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Breast Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Glioblastoma Hemangiosarcoma Prostatic Neoplasms Carcinoma Carcinoma, Hepatocellular Colorectal Neoplasms Leukemia, Myelogenous, Chronic, BCR-ABL Positive Ovarian Neoplasms Stomach Neoplasms

ATC Classification

L01EH02

neratinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

Kd 141 meas. best 9.43

IC50 103 meas. best 10.7

EC50 6 meas. best 8.7

Ki 3 meas. best 8.35

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Epidermal growth factor receptor CHEMBL203	IC50	10.7	8.0748	0.0	27
Epidermal growth factor receptor CHEMBL203	Kd	9.43	8.8521	0.4	14
Mitogen-activated protein kinase kinase kinase kinase 5 CHEMBL4852	Kd	9.19	8.54	0.7	2
NCI-N87 CHEMBL614197	IC50	9.19	8.65	0.6	2
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	IC50	9.0	7.8959	1.0	17
SK-BR-3 CHEMBL613834	IC50	8.74	7.5675	1.8	4
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	EC50	8.7	7.79	2.0	5
BT-474 CHEMBL614529	IC50	8.69	8.345	2.1	2
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	Kd	8.62	8.62	2.4	1
Epidermal growth factor receptor CHEMBL203	EC50	8.52	8.52	3.0	1
BaF3 CHEMBL614524	IC50	8.52	6.7256	3.0	9
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.46	7.605	3.5	2
Epidermal growth factor receptor CHEMBL203	Ki	8.35	8.255	4.5	2
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	Kd	8.22	8.22	6.0	1
Unchecked CHEMBL612545	Ki	8.2	8.2	6.3	1
Serine/threonine-protein kinase 24 CHEMBL5082	Kd	8.19	8.19	6.5	1
Serine/threonine-protein kinase 24 CHEMBL5082	IC50	8.15	8.15	7.0	1
Serine/threonine-protein kinase 26 CHEMBL5941	IC50	8.15	8.15	7.0	1
Serine/threonine-protein kinase 26 CHEMBL5941	Kd	8.13	7.08	7.4	2
Mitogen-activated protein kinase kinase kinase kinase 3 CHEMBL5432	Kd	8.11	6.935	7.7	2
Receptor tyrosine-protein kinase erbB-3 CHEMBL5838	Kd	8.11	8.11	7.7	1
Serine/threonine-protein kinase 25 CHEMBL5552	Kd	7.92	7.92	12.0	1
Unchecked CHEMBL612545	IC50	7.92	6.74	12.0	10
Serine/threonine-protein kinase 10 CHEMBL3981	Kd	7.89	6.68	13.0	2
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	Kd	7.85	6.675	14.0	2
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	7.8	7.8	16.0	1
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	IC50	7.72	7.72	19.0	1
Dual specificity mitogen-activated protein kinase kinase 2 CHEMBL2964	Kd	7.58	6.49	26.0	2
Misshapen-like kinase 1 CHEMBL5518	Kd	7.54	7.54	29.0	1
NUGC-4 CHEMBL613519	IC50	7.42	7.42	38.1	1
Mitogen-activated protein kinase kinase kinase 4 CHEMBL4853	Kd	7.41	6.73	39.0	2
Calu-3 CHEMBL614534	IC50	7.27	7.27	54.0	1
NCI-H3255 CHEMBL4296476	IC50	7.26	7.26	55.0	1
Serine/threonine-protein kinase 3 CHEMBL4708	IC50	7.24	7.24	58.0	1
Serine/threonine-protein kinase 3 CHEMBL4708	Kd	7.24	7.24	58.0	1
Dual specificity mitogen-activated protein kinase kinase 5 CHEMBL4948	Kd	7.2	7.2	63.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	7.18	6.58	66.0	2
Serine/threonine-protein kinase PAK 2 CHEMBL4487	Kd	7.1	7.1	79.0	1
Tyrosine-protein kinase Blk CHEMBL2250	Kd	7.07	7.07	85.0	1
A-431 CHEMBL614069	IC50	7.07	6.37	86.0	2
HCC827 CHEMBL4296422	IC50	7.03	7.03	94.0	1
Mitogen-activated protein kinase kinase kinase kinase 1 CHEMBL5749	Kd	7.03	7.03	93.0	1
eIF-2-alpha kinase GCN2 CHEMBL5358	Kd	7.02	7.02	96.0	1
PC-9 CHEMBL614102	IC50	7.02	7.02	96.0	1
Tyrosine-protein kinase Lck CHEMBL258	Kd	6.92	6.46	120.0	2
Mitogen-activated protein kinase kinase kinase 3 CHEMBL5970	Kd	6.89	6.89	130.0	1
TRAF2 and NCK-interacting protein kinase CHEMBL4527	Kd	6.85	6.85	140.0	1
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	6.85	6.85	140.0	1
NCI-H1975 CHEMBL614348	IC50	6.82	6.82	153.0	1
Tyrosine-protein kinase BTK CHEMBL5251	Kd	6.8	6.36	160.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	2388.0	ng.hr.mL-1	Rattus norvegicus
AUC	1466.0	ng.hr.mL-1	Rattus norvegicus
CL	126.0	mL.min-1.g-1	Mus musculus
CL	42.0	mL.min-1.g-1	Homo sapiens
CL	20.8	mL.min-1.kg-1	Rattus norvegicus
Cmax	360.83	nM	Rattus norvegicus
F	18.2	%	Rattus norvegicus
T1/2	0.6833	hr	-
T1/2	4.38	hr	Rattus norvegicus
T1/2	2.97	hr	Rattus norvegicus
Tmax	2.67	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Epidermal growth factor receptor	IC50	=	0.02	nM	10.7	Inhibition of human N-terminal GST-tagged EGFR L858R mutant (669 to 1210 residue...	32931277
Epidermal growth factor receptor	IC50	=	0.02	nM	10.7	Inhibition of human N-terminal GST-tagged EGFR (669 to 1210 residues) expressed ...	32931277
Epidermal growth factor receptor	IC50	=	0.08	nM	10.1	Inhibition of human EGFR in presence of 1 uM ATP	17416531
Epidermal growth factor receptor	IC50	=	0.18	nM	9.74	Inhibition of human EGFR in presence of 1 mM ATP	17416531
Epidermal growth factor receptor	Kd	=	0.37	nM	9.43	Binding constant for EGFR(G719C) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.37	nM	9.43	Binding constant for EGFR(L861Q) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	0.39	nM	9.41	Inhibition of EGFR (unknown origin)	35319895
Epidermal growth factor receptor	IC50	=	0.58	nM	9.24	Inhibition of wild type human N-terminal GST tagged EGFR (669 to 1210 residues) ...	35319895
Epidermal growth factor receptor	Kd	=	0.61	nM	9.21	Binding constant for EGFR(L747-E749del, A750P) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.63	nM	9.2	Binding constant for EGFR(S752-I759del) kinase domain	22037378
Mitogen-activated protein kinase kinase kinase kinase 5	Kd	=	0.65	nM	9.19	Binding constant for MAP4K5 kinase domain	22037378
NCI-N87	IC50	=	0.64	nM	9.19	Antiproliferative activity against human NCI-N87 cells assessed as inhibition of...	35319895
Epidermal growth factor receptor	Kd	=	0.67	nM	9.17	Binding constant for EGFR(L858R) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	0.8	nM	9.1	Inhibition of human N-terminal GST-tagged EGFR L858R/T790M mutant (669 to 1210 r...	32931277
Epidermal growth factor receptor	Kd	=	0.91	nM	9.04	Binding constant for EGFR(G719S) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.93	nM	9.03	Binding constant for EGFR(L747-S752del, P753S) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition of EGFR by HTRF assay	19028424
Epidermal growth factor receptor	Kd	=	1.0	nM	9.0	Binding constant for EGFR(L747-T751del,Sins) kinase domain	22037378
Receptor tyrosine-protein kinase erbB-2	IC50	=	1.0	nM	9.0	Inhibition of ERBb2 by HTRF assay	19028424
Epidermal growth factor receptor	Kd	=	1.1	nM	8.96	Binding affinity to wild-type human partial length EGFR (R669 to V1011 residues)...	30973735

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	HEK-293T	346
-	10.6019/CHEMBL4689842	U2OS	345
-	10.6019/CHEMBL4689842	Fibroblast	342
18077425	10.1073/pnas.0707498104	NON-PROTEIN TARGET	232
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
18077425	10.1073/pnas.0707498104	COLO	14
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
20033049	10.1038/nature08622	BaF3	11
38518121	10.1021/acs.jmedchem.3c02302	ADMET	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
26254279	10.18632/oncotarget.4214	Epidermal growth factor receptor and ErbB2 (HER1 and HER2)	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
15715478	10.1021/jm040159c	Mus musculus	7
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
32931277	10.1021/acs.jmedchem.0c00870	Unchecked	7
18077425	10.1073/pnas.0707498104	HeLa	6
38134304	10.1021/acs.jmedchem.3c01502	Epidermal growth factor receptor	6
35319895	10.1021/acs.jmedchem.1c00710	Receptor tyrosine-protein kinase erbB-2	6
32931277	10.1021/acs.jmedchem.0c00870	ADMET	6
32931277	10.1021/acs.jmedchem.0c00870	Epidermal growth factor receptor	5

Data from ChEMBL 36 via Core Engine