Compound Detail

CHEMBL1173655

AFATINIB

💊 Approved Drug

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💊 Approved Drug

CN(C)C/C=C/C(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@H]1CCOC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1173655
Name	AFATINIB
Phase	Approved
Structure Type	MOL
InChI Key	ULXXDDBFHOBEHA-CWDCEQMOSA-N
Therapeutic	✓ Yes

Known Names

Afatinib Bibw 2992 BIBW-2992 BIBW2992 Gilotrif Giotrif NSC-750691 Tomtovok Tovok

633

Targets

926

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Molecular Properties

485.9

MW (Da)

4.39

ALogP

HBA

HBD

88.6

PSA (Å²)

0.46

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2013
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral

Flags

Chemical Probe

USAN Stem	-tinib
USAN Year	2010

Extended Properties

Molecular Formula	C24H25ClFN5O3
MW	485.95
Aromatic Rings	3
Heavy Atoms	34
NP-Likeness	-1.14

Indications

Breast Neoplasms Breast Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Carcinoma, Squamous Cell Head and Neck Neoplasms Head and Neck Neoplasms Neoplasms Neoplasms Chordoma Colorectal Neoplasms Esophageal Neoplasms Gallbladder Neoplasms Lung Neoplasms Lung Neoplasms Multiple Myeloma Paraganglioma Prostatic Neoplasms Small Cell Lung Carcinoma Urogenital Neoplasms

ATC Classification

L01EB03

afatinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 826 meas. best 10.64

Kd 79 meas. best 10.0

EC50 18 meas. best 8.52

Ki 3 meas. best 9.19

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
A-431 CHEMBL614069	IC50	10.64	7.425	0.0	6
Epidermal growth factor receptor CHEMBL203	IC50	10.1	8.6208	0.1	104
Epidermal growth factor receptor CHEMBL203	Kd	10.0	9.6164	0.1	14
PC-9 CHEMBL614102	IC50	10.0	8.0214	0.1	7
HCC827 CHEMBL4296422	IC50	9.64	9.5	0.2	2
Unchecked CHEMBL612545	IC50	9.38	7.4486	0.4	28
NON-PROTEIN TARGET CHEMBL3879801	IC50	9.3	7.09	0.5	5
Epidermal growth factor receptor CHEMBL203	Ki	9.19	8.265	0.7	2
Unchecked CHEMBL612545	Ki	9.12	9.12	0.8	1
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	IC50	9.0	8.7133	1.0	3
SK-BR-3 CHEMBL613834	IC50	8.92	8.92	1.2	1
BaF3 CHEMBL614524	IC50	8.8	7.8688	1.6	8
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	IC50	8.7	7.88	2.0	17
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	EC50	8.52	7.6125	3.0	4
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	Kd	8.3	8.3	5.0	1
HDLM-2 CHEMBL2366231	IC50	8.24	8.24	5.7	1
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	Kd	8.2	8.2	6.3	1
Epidermal growth factor receptor CHEMBL203	EC50	8.12	7.752	7.5	5
Kasumi 1 CHEMBL613988	IC50	8.04	8.04	9.1	1
HCC2218 CHEMBL2366221	IC50	8.01	8.01	9.9	1
LoVo CHEMBL614721	IC50	7.82	6.75	15.0	2
KARPAS-45 CHEMBL2366305	IC50	7.78	7.78	16.7	1
HSC-4 CHEMBL1075469	IC50	7.76	7.76	17.5	1
CHL-1 CHEMBL1075422	IC50	7.74	7.74	18.4	1
KY821 CHEMBL2366190	IC50	7.69	7.69	20.6	1
NCI-H1975 CHEMBL614348	IC50	7.66	6.3147	22.0	17
NCI-N87 CHEMBL614197	IC50	7.56	7.56	27.7	1
DOK CHEMBL1075435	IC50	7.5	7.5	31.9	1
DSH1 CHEMBL2366079	IC50	7.48	7.48	33.1	1
MDA-MB-175-VII CHEMBL1075497	IC50	7.47	7.47	34.2	1
NCI-H2170 CHEMBL1075534	IC50	7.43	7.43	37.3	1
A549 CHEMBL392	IC50	7.3	5.7192	50.0	13
BT-474 CHEMBL614529	IC50	7.3	7.3	49.9	1
EFO-27 CHEMBL1075441	IC50	7.29	7.29	51.8	1
NCI-H720 CHEMBL2366105	IC50	7.27	7.27	53.2	1
PC-14 CHEMBL614140	IC50	7.25	7.25	56.7	1
EC-GI-10 CHEMBL2366240	IC50	7.23	7.23	59.1	1
KYSE-450 CHEMBL1075488	IC50	7.22	7.22	59.8	1
BPH-1 CHEMBL2366131	IC50	7.22	7.22	59.9	1
NCI-H292 CHEMBL614733	IC50	7.21	7.21	60.9	1
H9 CHEMBL614806	IC50	7.15	7.15	71.3	1
NCI-H526 CHEMBL2366102	IC50	7.11	7.11	78.2	1
NCI-H1623 CHEMBL1075517	IC50	7.1	7.1	80.2	1
Cyclin-G-associated kinase CHEMBL4355	Kd	7.1	6.65	79.0	3
Ca9-22 CHEMBL1075404	IC50	7.08	7.08	83.5	1
KYSE-140 CHEMBL1075484	IC50	7.08	7.08	83.3	1
AU565 CHEMBL1075393	IC50	7.07	7.07	85.0	1
ZR-75-30 CHEMBL1075613	IC50	7.02	7.02	95.5	1
BaF3 CHEMBL614524	EC50	7.01	7.01	97.0	1
CL97 CHEMBL4513122	IC50	7.0	7.0	100.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	0.49	uM.hr	Mus musculus
AUC	276.8	ng.hr.mL-1	Rattus norvegicus
AUC	324.5	ng.hr.mL-1	Rattus norvegicus
AUC	1063.0	ng.hr.mL-1	Rattus norvegicus
AUC	676.0	ng.hr.mL-1	Rattus norvegicus
AUC	3.198	uM.hr	Mus musculus
AUC	0.972	uM.hr	Mus musculus
AUC	1.075	uM.hr	Mus musculus
AUC	1.231	uM.hr	Mus musculus
AUC	2.156	uM.hr	Mus musculus
AUC	5.062	uM.hr	Mus musculus
CL	270.0	mL.min-1.kg-1	Mus musculus
CL	54.17	mL.min-1.kg-1	Rattus norvegicus
CL	79.2	mL.min-1.kg-1	Rattus norvegicus
CL	9.4	mL.min-1.g-1	Mus musculus
CL	1.4	mL.min-1.g-1	Homo sapiens
CL	8.0	mL.min-1.g-1	Homo sapiens
Cmax	130.0	nM	Mus musculus
Cmax	0.0752	ug.mL-1	Rattus norvegicus
Cmax	285.0	nM	Mus musculus
Cmax	83.0	nM	Mus musculus
Cmax	80.0	nM	Mus musculus
Cmax	309.0	nM	Mus musculus
Cmax	236.0	nM	Mus musculus
Cmax	667.0	nM	Mus musculus
F	37.4	%	Mus musculus
F	62.3	%	Rattus norvegicus
F	15.9	%	Rattus norvegicus
Fu	0.041	-	Rattus norvegicus
Fu	0.0054	-	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
A-431	IC50	=	0.023	nM	10.64	Antiproliferative activity against human A431 cells after 72 hrs by SRB assay	24183742
Epidermal growth factor receptor	IC50	=	0.08	nM	10.1	Inhibition of wild type EGFR (unknown origin) pre-incubated for 10 mins followed...	37087886
Epidermal growth factor receptor	Kd	=	0.1	nM	10.0	Binding constant for EGFR(G719C) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	0.1	nM	10.0	Inhibition of recombinant human N-terminal GST tagged EGFR d746-750 mutant (669 ...	29523467
PC-9	IC50	=	0.1	nM	10.0	Antiproliferative activity against human PC9 cells harboring EGFR exon-19 del mu...	30554954
Epidermal growth factor receptor	Kd	=	0.11	nM	9.96	Binding constant for EGFR(E746-A750del) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.12	nM	9.92	Binding constant for EGFR(L747-S752del, P753S) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.12	nM	9.92	Binding constant for EGFR(L747-T751del,Sins) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.14	nM	9.85	Binding constant for EGFR(L747-E749del, A750P) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.14	nM	9.85	Binding constant for EGFR(S752-I759del) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	0.161	nM	9.79	Inhibition of EGFR A763-Y764 ins FQEA mutant (unknown origin)	36804726
Epidermal growth factor receptor	IC50	=	0.166	nM	9.78	Inhibition of EGFR D770-N771 ins NPG mutant (unknown origin)	36804726
Epidermal growth factor receptor	IC50	=	0.19	nM	9.72	Inhibition of wild type EGFR (unknown origin) expressed in baculovirus expressio...	24183742
Epidermal growth factor receptor	Kd	=	0.19	nM	9.72	Binding constant for EGFR(G719S) kinase domain	22037378
Epidermal growth factor receptor	Kd	=	0.2	nM	9.7	Binding constant for EGFR(L858R) kinase domain	22037378
Epidermal growth factor receptor	IC50	=	0.2	nM	9.7	Inhibition of recombinant human N-terminal GST tagged EGFR L858R mutant (669 to ...	29523467
Epidermal growth factor receptor	IC50	=	0.1995	nM	9.7	Inhibition of wild type N-terminal GST-tagged EGFR (669 to 1210 residues) (unkno...	38746885
Epidermal growth factor receptor	IC50	=	0.2	nM	9.7	Inhibition of EGFR E746_A750del mutant expressing in human HCC827 cells assessed...	18408761
Epidermal growth factor receptor	Kd	=	0.23	nM	9.64	Binding constant for EGFR(L861Q) kinase domain	22037378
HCC827	IC50	=	0.23	nM	9.64	Antiproliferative activity against human HCC827 cells by CellTiter-Glo assay	38518121

Literature References

PubMed	DOI	Target Context	# Activities
18408761	10.1038/onc.2008.109	Epidermal growth factor receptor	21
28287083	10.1038/ncomms14768	Unchecked	19
18408761	10.1038/onc.2008.109	Unchecked	18
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
31560541	10.1021/acs.jmedchem.9b00722	ADMET	14
18408761	10.1038/onc.2008.109	ADMET	12
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
28287083	10.1038/ncomms14768	Epidermal growth factor receptor	12
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
37984296	10.1016/j.ejmech.2023.115939	A549	9
26254279	10.18632/oncotarget.4214	Epidermal growth factor receptor and ErbB2 (HER1 and HER2)	9
32739648	10.1016/j.ejmech.2020.112640	Epidermal growth factor receptor	9
18408761	10.1038/onc.2008.109	Mus musculus	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
-	10.6019/CHEMBL5724696	U2OS	8
26310890	10.1016/j.ejmech.2015.08.026	Rattus norvegicus	7
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
32931277	10.1021/acs.jmedchem.0c00870	Unchecked	7
36804726	10.1016/j.bmc.2023.117202	Epidermal growth factor receptor	7
32931277	10.1021/acs.jmedchem.0c00870	ADMET	6

Data from ChEMBL 36 via Core Engine