Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGKNB4)

• DTT Name: Epidermal growth factor receptor (EGFR)
• Synonyms: Receptor tyrosine-protein kinase erbB-1; Proto-oncogene c-ErbB-1; HER1; ERBB1; ERBB
• Gene Name: EGFR
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: EGFR_HUMAN
• TTD ID: T59328
• EC Number: EC 2.7.10.1
• Sequence:
  MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
  VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
  VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
  QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
  TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
  VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
  NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
  ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
  FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
  LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
  GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
  ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
  GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
  CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
  RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
  GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
  FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
  QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
  SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
  TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
  APQSSEFIGA
• Function: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance (By similarity).
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  ErbB signaling pathway (hsa04012)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 signaling pathway (hsa04066)
  FoxO signaling pathway (hsa04068)
  Endocytosis (hsa04144)
  PI3K-Akt signaling pathway (hsa04151)
  Dorso-ventral axis formation (hsa04320)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Gap junction (hsa04540)
  Regulation of actin cytoskeleton (hsa04810)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Oxytocin signaling pathway (hsa04921)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Hepatitis C (hsa05160)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Bladder cancer (hsa05219)
  Non-small cell lung cancer (hsa05223)
  Central carbon metabolism in cancer (hsa05230)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  PLCG1 events in ERBB2 signaling (R-HSA-1251932)
  PIP3 activates AKT signaling (R-HSA-1257604)
  GRB2 events in EGFR signaling (R-HSA-179812)
  GAB1 signalosome (R-HSA-180292)
  SHC1 events in EGFR signaling (R-HSA-180336)
  EGFR downregulation (R-HSA-182971)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  PI3K events in ERBB2 signaling (R-HSA-1963642)
  EGFR Transactivation by Gastrin (R-HSA-2179392)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Constitutive Signaling by EGFRvIII (R-HSA-5637810)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)

Molecular Interaction Atlas (MIA) of This DTT

19 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25	Approved	[2]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[3]
Cetuximab	DMLNCE0	Colorectal cancer	2B91.Z	Approved	[1]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[4]
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[4]
Erlotinib	DMCMBHA	Adrenal gland neoplasm		Approved	[5]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[6]
HEGF	DMN0S1G	Diabetic foot ulcer	BD54	Approved	[7]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[8]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[9]
Necitumumab	DMKOJSN	Colorectal cancer	2B91.Z	Approved	[10]
NERATINIB MALEATE	DMEDU7B	HER2/NEU overexpressing breast cancer	2C60-2C65	Approved	[11]
Nitroglycerin	DMQ2491	Angina pectoris	BA40	Approved	[7]
Osimertinib	DMRJLAT	Non-small-cell lung cancer	2C25.Y	Approved	[12]
Panitumumab	DMQPD1F	Colorectal cancer	2B91.Z	Approved	[13]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[15]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Icotinib hydrochloride	DM5GFIK	Non-small-cell lung cancer	2C25.Y	Registered	[17]

65 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A140	DMEAWJT	Head and neck cancer	2D42	Phase 3	[18]
Almonertinib	DMCHA27	Non-small-cell lung cancer	2C25.Y	Phase 3	[19]
ASP1929	DMR71ST	Head and neck cancer	2D42	Phase 3	[20]
CO-1686	DMWZ2TU	Lung cancer	2C25.0	Phase 3	[21]
DE-766	DM0GUV2	Gastric adenocarcinoma	2B72	Phase 3	[4]
EGF816	DMCMJRA	Non-small-cell lung cancer	2C25.Y	Phase 3	[22]
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[23]
Rindopepimut	DMP6IMQ	Brain cancer	2A00	Phase 3	[10]
SYM-004	DMOVEDH	Metastatic colorectal cancer	2B91	Phase 3	[24]
Zalutumumab	DM52QEZ	Head and neck cancer	2D42	Phase 3	[4]
Indium-111	DMC3794	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[25]
Varlitinib	DMDG8Q3	Metastatic biliary tract neoplasms	2C14-2C17	Phase 2/3	[26]
ABT-414	DMGUTPN	Glioblastoma multiforme	2A00.0	Phase 2	[27]
ABX-EGF	DM91U0R	N. A.	N. A.	Phase 2	[28]
ASP8273	DMHLXUY	Non-small-cell lung cancer	2C25.Y	Phase 2	[29]
BMS-599626	DMDPQV5	Solid tumour/cancer	2A00-2F9Z	Phase 2	[30]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[31]
CetuGEX	DMAWKSM	Solid tumour/cancer	2A00-2F9Z	Phase 2	[32]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[16]
Depatuxizumab	DM7GPMB	Glioblastoma of brain	2A00.00	Phase 2	[33]
HER1-VSSP vaccine	DMX6B95	Solid tumour/cancer	2A00-2F9Z	Phase 2	[34]
HM-78136B	DMZ3BER	HER2-positive breast cancer	2C60-2C65	Phase 2	[35]
Matuzumab	DM2458E	Gastric adenocarcinoma	2B72	Phase 2	[36]
MEHD-7945A	DMHOF7T	Colorectal cancer	2B91.Z	Phase 2	[26]
Pelitinib	DMIW453	Lymphoma	2A80-2A86	Phase 2	[37]
RM-1929	DMVU1R9	Head and neck cancer	2D42	Phase 2	[35]
Tarloxotinib	DMA7ISF	Non-small-cell lung cancer	2C25.Y	Phase 2	[38]
TT-100	DMZE6Y9	Non-small-cell lung cancer	2C25.Y	Phase 2	[39]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
AFM24	DMFTZX0	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[40]
BDTX-189	DMODTX5	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[41]
CART-EGFR	DM3I267	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[42]
EGFR CART	DMDWCOF	Colorectal cancer	2B91.Z	Phase 1/2	[43]
EMB-01	DMCAUKW	Neoplasm	2A00-2F9Z	Phase 1/2	[44]
EMD 55900	DMMD10S	Glioma	2A00.0	Phase 1/2	[28]
SN-32793	DMEJT5Z	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[4]
Sym013	DMZM6I2	Epithelial ovarian cancer	2B5D	Phase 1/2	[33]
Sym015	DM9B7Z5	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[33]
TAK-186	DM6XL9A	Aggressive cancer	2A00-2F9Z	Phase 1/2	[45]
ZN-e4	DMLV4U1	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[46]
S-222611	DMQGH76	Malignant solid tumour	2C10-2F32	Phase 1b	[47]
AMG 595	DMJFKW3	Glioblastoma multiforme	2A00.0	Phase 1	[48]
Anti-EGFR CAR T	DMIVUX1	Glioma	2A00.0	Phase 1	[49]
Anti-HER3/EGFR DAF	DMDMNJ6	Metastatic epithelial tumour	2D60	Phase 1	[50]
AP32788	DMGDARN	Non-small-cell lung cancer	2C25.Y	Phase 1	[35]
AST-1306	DMD83WO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[51]
AZD9592	DMDPM67	Aggressive cancer	2A00-2F9Z	Phase 1	[52]
BCA101	DMM0VBU	Solid tumour/cancer	2A00-2F9Z	Phase 1	[53]
BIBX-1382	DM79XGM	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[54]
Cipatinib	DMJLNEF	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
CLN-081	DM05R4C	Non-small-cell lung cancer	2C25.Y	Phase 1	[55]
CUDC-101	DM9ZOMD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[56]
CX-904	DMOOHDN	Colorectal cancer	2B91.Z	Phase 1	[57]
D2C7	DMIMK84	Glioblastoma of brain	2A00.00	Phase 1	[58]
EGFR806-specific CAR T cell	DM3AD65	Atypical teratoid/rhabdoid tumour	2A00.1Y	Phase 1	[59]
HER-2/HER-1 vaccine	DMXETUQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
IMGN289	DMT9MHE	Solid tumour/cancer	2A00-2F9Z	Phase 1	[60]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[61]
LY3164530	DM9RTXM	Advanced cancer	2A00-2F9Z	Phase 1	[62]
MCLA-158	DMF0O3X	Solid tumour/cancer	2A00-2F9Z	Phase 1	[63]
MM-151	DMXQHZC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]
MR1-1	DME7JFM	Brain cancer	2A00	Phase 1	[64]
PF-05230907	DM7GSZL	Nontraumatic intracerebral hemorrhage	8B00.4	Phase 1	[65]
SI-B001	DMDSFEB	Metastatic epithelial tumour	2D60	Phase 1	[66]
SYN004	DM0EZ69	Solid tumour/cancer	2A00-2F9Z	Phase 1	[33]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pyrrolo[2,3-d]pyrimidine derivative 24	DMZQF9R	N. A.	N. A.	Patented	[67]

9 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PKI166	DMSQ794	Esophageal cancer	2B70	Discontinued in Phase 2	[68]
RG7160	DM5KJGB	Metastatic colorectal cancer	2B91	Discontinued in Phase 2	[69]
AZD4769	DMA3OWI	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[70]
PD-153035	DM7KJTI	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[71]
TAK165	DMBE5OF	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[16]
AZD-9935	DMFE3CD	Solid tumour/cancer	2A00-2F9Z	Terminated	[74]
CGP-52411	DMIWUFC	Solid tumour/cancer	2A00-2F9Z	Terminated	[75]
CGP-53353	DM9VDZP	N. A.	N. A.	Terminated	[76]
Heparin-EGF-like factor	DMMXG2I	Gastrointestinal disease	DE2Z	Terminated	[77]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
111In-hEGF	DM9TQDE	Breast cancer	2C60-2C65	Preclinical	[72]
EGFR/IGFR tandem adnectin	DMZ3YP6	Solid tumour/cancer	2A00-2F9Z	Preclinical	[73]

104 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3-Bromo-phenyl)-(5-nitro-quinazolin-4-yl)-amine	DMHLF2S	Discovery agent	N.A.	Investigative	[78]
(3-Bromo-phenyl)-quinazolin-4-yl-amine	DMMIPZ8	Discovery agent	N.A.	Investigative	[79]
(E)-5-(4-Hydroxybenzylidene)-1-phenethylhydantoin	DM81JRF	Discovery agent	N.A.	Investigative	[80]
(S)-benzyl 4-chloro-3-oxobutan-2-ylcarbamate	DMA43NY	Discovery agent	N.A.	Investigative	[81]
10-hydroxy-18-methoxybetaenone	DM4R7X8	Discovery agent	N.A.	Investigative	[82]
2-(4,5-Dihydroxy-indan-1-ylidene)-malononitrile	DM4BFHR	Discovery agent	N.A.	Investigative	[83]
2-(5,6-Dihydroxy-indan-1-ylidene)-malononitrile	DMTC5Y9	Discovery agent	N.A.	Investigative	[83]
2-benzoyl-3-(3,4-dihydroxyphenyl)acrylonitrile	DMO97FR	Discovery agent	N.A.	Investigative	[81]
2-cyano-3-(3,4-dihydroxyphenyl)acrylamide	DMCN6PY	Discovery agent	N.A.	Investigative	[81]
2-methoxy-4-(2-nitrovinyl)phenol	DMEAVD2	Discovery agent	N.A.	Investigative	[81]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[84]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[84]
3-(3-Chloro-phenyl)-5,7-dihydroxy-chromen-4-one	DMD4O6V	Discovery agent	N.A.	Investigative	[85]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[84]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[84]
3-Pyridin-4-yl-quinoline-6,7-diol	DME1TUK	Discovery agent	N.A.	Investigative	[86]
4-(2-nitroprop-1-enyl)benzene-1,2-diol	DMCHTI0	Discovery agent	N.A.	Investigative	[81]
4-(2-nitrovinyl)benzene-1,2-diol	DM62ZRE	Discovery agent	N.A.	Investigative	[81]
4-(2-nitrovinyl)phenol	DMPTVR2	Discovery agent	N.A.	Investigative	[81]
4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinazoline	DMNBLQ8	Discovery agent	N.A.	Investigative	[87]
4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinoline	DMK6JV7	Discovery agent	N.A.	Investigative	[87]
4-(3-Bromo-phenylamino)-quinazoline-6,7-diol	DM1Q5KV	Discovery agent	N.A.	Investigative	[79]
4-(4-(2-nitrovinyl)phenoxysulfonyl)benzoic acid	DMWBVMH	Discovery agent	N.A.	Investigative	[81]
4-(5-Bromoindole-3-yl)-6,7-dimethoxyquinazoline	DMLSGU1	Discovery agent	N.A.	Investigative	[88]
4-acrylamido-N-(3-bromophenyl)-2-hydroxybenzamide	DMN2TMS	Discovery agent	N.A.	Investigative	[89]
4-biphenyl-2-ylethynyl-6,7-dimethoxy-quinazoline	DMYUL9J	Discovery agent	N.A.	Investigative	[90]
4557W	DMLE0I7	Discovery agent	N.A.	Investigative	[91]
5,6-Bis-p-tolylamino-isoindole-1,3-dione	DM6A4LM	Discovery agent	N.A.	Investigative	[76]
5-acrylamido-N-(3-bromophenyl)-2-hydroxybenzamide	DMB7R95	Discovery agent	N.A.	Investigative	[89]
6,7-diethoxy-4-(4-phenylbut-1-enyl)quinazoline	DMI7FVJ	Discovery agent	N.A.	Investigative	[90]
6,7-diethoxy-4-(5-phenylpent-1-enyl)quinazoline	DMFVT8A	Discovery agent	N.A.	Investigative	[90]
6,7-diethoxy-4-styrylquinazoline	DMVR4OW	Discovery agent	N.A.	Investigative	[90]
6,7-dimethoxy-4-(2-phenylethynyl)quinazoline	DMQTHV7	Discovery agent	N.A.	Investigative	[90]
6,7-dimethoxy-4-(3-phenoxyprop-1-ynyl)quinazoline	DMKO8QT	Discovery agent	N.A.	Investigative	[90]
6,7-dimethoxy-4-(4-phenylbut-1-ynyl)quinazoline	DMBI40Y	Discovery agent	N.A.	Investigative	[90]
6,7-dimethoxy-N-m-tolylquinazolin-4-amine	DMP8LXB	Discovery agent	N.A.	Investigative	[92]
6-chloro-N-(3-chlorophenyl)quinazolin-4-amine	DMPIFLA	Discovery agent	N.A.	Investigative	[93]
AFM-21	DM8U1IW	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
AG 112	DMDYS0L	Discovery agent	N.A.	Investigative	[94]
AG 9	DMSOUI0	Discovery agent	N.A.	Investigative	[94]
AG-213	DMT3ML6	Discovery agent	N.A.	Investigative	[88]
AG-538	DM9KIS8	Discovery agent	N.A.	Investigative	[81]
AGT-2000	DMP9QW0	Brain cancer	2A00	Investigative	[4]
AL-6802	DM3JNRC	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
Anti-EGFR humanized mabs	DMWLMV2	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
Anti-EGFR mab	DMW85FP	Discovery agent	N.A.	Investigative	[4]
ARX-AHD	DM15KLR	Breast cancer	2C60-2C65	Investigative	[4]
Benzo[g]quinazolin-4-yl-(3-bromo-phenyl)-amine	DMISHTB	Discovery agent	N.A.	Investigative	[79]
Benzyl-quinazolin-4-yl-amine	DMRW5J4	Discovery agent	N.A.	Investigative	[78]
Bmab-200	DM8AEQX	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
BPIQ-I	DMNHEUT	Discovery agent	N.A.	Investigative	[79]
CL-387785	DMLKFZC	Discovery agent	N.A.	Investigative	[92]
Cochliobolic acid	DMOUSWN	Discovery agent	N.A.	Investigative	[95]
EDP-13	DMLSMBI	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
EGFR inhibitor	DM7AYH4	Discovery agent	N.A.	Investigative	[96]
Epitinib	DM1C8FW	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
FHT-2107	DMH7LDX	Discovery agent	N.A.	Investigative	[4]
GI-3000	DMU92RC	Non-small-cell lung cancer	2C25.Y	Investigative	[4]
HDS-029	DMLRUVA	Discovery agent	N.A.	Investigative	[97]
HKI-9924129	DM5LR2B	Gram-positive bacterial infection	1B74-1G40	Investigative	[98]
HM-61713B	DMNOFTX	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
HTS-00213	DMQ8ADE	Discovery agent	N.A.	Investigative	[92]
HTS-02876	DMVUTJ5	Discovery agent	N.A.	Investigative	[92]
HTS-05058	DM3F4IQ	Discovery agent	N.A.	Investigative	[96]
ICR 62	DMH4KGX	Discovery agent	N.A.	Investigative	[28]
IPS-01003	DM0T8ZU	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
LA22-radioimmunoconjugates	DMY6K2A	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
LAVENDUSTIN A	DMH3X06	Discovery agent	N.A.	Investigative	[99]
mabionHER2	DMJX2CS	Breast cancer	2C60-2C65	Investigative	[4]
MDP-01	DM8ZK12	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
MG-111	DMG56EU	Discovery agent	N.A.	Investigative	[100]
MT-062	DM5PD0G	Melanoma	2C30	Investigative	[4]
N*4*-(3-Bromo-phenyl)-quinazoline-4,6,7-triamine	DMFWN5U	Discovery agent	N.A.	Investigative	[79]
N*4*-(3-Bromo-phenyl)-quinazoline-4,6-diamine	DMUI8RC	Discovery agent	N.A.	Investigative	[101]
N*4*-(3-Bromo-phenyl)-quinazoline-4,7-diamine	DMO56XY	Discovery agent	N.A.	Investigative	[78]
N*4*-Benzyl-pyrido[4,3-d]pyrimidine-4,7-diamine	DMK674I	Discovery agent	N.A.	Investigative	[102]
N-(4-(phenylamino)quinazolin-6-yl)acrylamide	DMI74KM	N. A.	N. A.	Investigative	[103]
N-(4-m-Tolylamino-quinazolin-6-yl)-acrylamide	DMEBGF1	Discovery agent	N.A.	Investigative	[104]
N-(4-m-Tolylamino-quinazolin-7-yl)-acrylamide	DMG6RTJ	Discovery agent	N.A.	Investigative	[104]
N4-(3-chlorophenyl)quinazoline-4,6-diamine	DM561Z7	Discovery agent	N.A.	Investigative	[105]
N4-(3-methylphenyl)-4,6-quinazolinediamine	DMDRYJ7	Discovery agent	N.A.	Investigative	[106]
NRC-2694	DMXP03H	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
ON-128	DMTNKBW	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
OSI-75	DM5IGN7	Discovery agent	N.A.	Investigative	[107]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[98]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[98]
PD-158780	DMQXYE9	Discovery agent	N.A.	Investigative	[102]
PD-168393	DMN8M5P	Discovery agent	N.A.	Investigative	[103]
PD182905	DMXLW4F	Discovery agent	N.A.	Investigative	[108]
PF 5208766	DMY45K1	Discovery agent	N.A.	Investigative	[109]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[110]
PMID8568816C56	DMG3ZD1	Discovery agent	N.A.	Investigative	[111]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[112]
RG-50810	DMUR9LM	Discovery agent	N.A.	Investigative	[81]
RM-6427	DM87Z3Y	Cryptosporidium infection	1A32	Investigative	[4]
Ro-4396686	DM5DMCH	Discovery agent	N.A.	Investigative	[113]
RX-1792	DMKYNGE	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
SYM-011	DMKIDRY	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
TGF alpha	DMOX3AH	Cerebrovascular ischaemia	8B1Z	Investigative	[4]
Theliatinib	DMRVXFN	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
Tyrphostin ag-1478	DM87ZIH	Discovery agent	N.A.	Investigative	[85]
WHI-P154	DMYHWS1	Diffuse large B-cell lymphoma	2A81	Investigative	[114]
WZ-3146	DMBWUR0	Lung cancer	2C25.0	Investigative	[4]
YH013	DMQ0474	Aggressive cancer	2A00-2F9Z	Investigative	[115]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Head and neck cancer	2C82	Head and neck tissue	5.84E-05	0.32	0.55
Neuroectodermal tumour	2C82	Nervous tissue	8.30E-26	0.06	0.13
Breast cancer	2C82	Breast tissue	1.04E-65	-0.89	-1.53
Lung cancer	2C82	Lung tissue	1.65E-01	-0.04	-0.09
Glioma	2C82	Brainstem tissue	2.09E-05	0.4	190.08
Glioma	2C82	White matter	6.32E-04	0.39	1.69
Prostate cancer	2C82	Prostate	7.43E-04	-0.59	-0.82
Ovarian cancer	2C82	Ovarian tissue	9.25E-01	-0.01	-0.03
Bladder cancer	2C82	Bladder tissue	5.87E-01	0.09	0.29
Rectal cancer	2C82	Rectal colon tissue	1.07E-02	-0.25	-1.63
Melanoma	2C82	Skin	1.60E-01	-0.34	-0.23
Psoriasis	EA90	Skin	1.86E-07	-0.27	-0.42
Gastric cancer	2C82	Gastric tissue	2.52E-01	-0.42	-2.17
Ureter cancer	2C82	Urothelium	5.34E-01	-0.07	-0.71

References

• [1] Molecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade. Mol Cancer Ther. 2002 May;1(7):507-14.
• [2] Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
• [3] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1797).
• [5] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [6] Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
• [7] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [8] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme. Curr Opin Mol Ther. 2010 Dec;12(6):741-54.
• [11] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [12] AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.
• [13] Integration of panitumumab into the treatment of colorectal cancer. Crit Rev Oncol Hematol. 2010 Apr;74(1):16-26.
• [14] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [15] Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
• [16] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [17] Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors. Lung Cancer. 2011 Aug;73(2):195-202.
• [18] Clinical pipeline report, company report or official report of Klus Pharma
• [19] Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial. J Thorac Oncol. 2020 Dec;15(12):1907-1918.
• [20] ClinicalTrials.gov (NCT04305795) An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors. U.S. National Institutes of Health.
• [21] Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1700-9.
• [22] Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov. 2013 Dec;3(12):1404-15.
• [23] Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cyst... Bioorg Med Chem. 2007 Jun 1;15(11):3635-48.
• [24] Sym004, a novel EGFR antibody mixture, can overcome acquired resistance to cetuximab. Neoplasia. 2013 Oct;15(10):1196-206.
• [25] Characterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody. Mol Cancer Ther. 2015 May;14(5):1141-51.
• [26] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [27] Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development. Mar Drugs. 2014 January; 12(1): 255-278.
• [28] Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer. 2002 Mar 1;94(5):1593-611.
• [29] Phase I dose escalation study of ASP8273, a mutant-selective irreversible EGFR inhibitor, in subjects with EGFR mutation positive NSCLC, Journal of Clinical Oncology, Vol 33, No 15_suppl (May 20 Supplement), 2015: 8083.
• [30] AC480, formerly BMS-599626, a pan Her inhibitor, enhances radiosensitivity and radioresponse of head and neck squamous cell carcinoma cells in vitro and in vivo. Invest New Drugs. 2011 Aug;29(4):554-61.
• [31] Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.
• [32] Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol Ther. 2011 May 1;11(9):777-92.
• [33] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [34] Active antimetastatic immunotherapy in Lewis lung carcinoma with self EGFR extracellular domain protein in VSSP adjuvant. Int J Cancer. 2006 Nov 1;119(9):2190-9.
• [35] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [36] Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization. Cancer Cell. 2008 Apr;13(4):365-73.
• [37] EGFR tyrosine kinase inhibitor pelitinib regulates radiation-induced p65-dependent telomerase activation in squamous cell carcinoma.Radiat Res.2013 Mar;179(3):304-12.
• [38] Tarloxotinib Is a Hypoxia-Activated Pan-HER Kinase Inhibitor Active Against a Broad Range of HER-Family Oncogenes. Clin Cancer Res. 2021 Mar 1;27(5):1463-1475.
• [39] BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
• [40] Clinical pipeline report, company report or official report of Affimed Therapeutics.
• [41] Clinical pipeline report, company report or official report of Black Diamond Therapeutics.
• [42] ClinicalTrials.gov (NCT01869166) Treatment of Chemotherapy Refractory EGFR(Epidermal Growth Factor Receptor) Positive Advanced Solid Tumors (CART-EGFR)
• [43] ClinicalTrials.gov (NCT03152435) EGFR CART Cells for Patients With Metastatic Colorectal Cancer
• [44] Clinical pipeline report, company report or official report of EpimAb Biotherapeutics.
• [45] Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186. J Immunother Cancer. 2022 Jun;10(6):e004336.
• [46] Clinical pipeline report, company report or official report of Zentalis Pharmaceuticals.
• [47] Clinical pipeline report, company report or official report of Shionogi (2011).
• [48] AMG 595, an Anti-EGFRvIII Antibody-Drug Conjugate, Induces Potent Antitumor Activity against EGFRvIII-Expressing Glioblastoma. Mol Cancer Ther. 2015 Jul;14(7):1614-24.
• [49] ClinicalTrials.gov (NCT02331693) CAR T Cells in Treating Patients With Malignant Gliomas Overexpressing EGFR
• [50] Company report (Biooncology)
• [51] AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo. PLoS One. 2011;6(7):e21487.
• [52] Clinical pipeline report, company report or official report of AstraZeneca
• [53] ClinicalTrials.gov (NCT04429542) Study of Safety and Tolerability of BCA101 Alone and in Combination With Pembrolizumab in Patients With EGFR-driven Advanced Solid Tumors. U.S. National Institutes of Health.
• [54] Phase I and pharmacokinetic study of BIBX 1382 BS, an epidermal growth factor receptor (EGFR) inhibitor, given in a continuous daily oral administration. Eur J Cancer. 2002 May;38(8):1072-80.
• [55] TAS6417, A Novel EGFR Inhibitor Targeting Exon 20 Insertion Mutations. Mol Cancer Ther. 2018 Aug;17(8):1648-1658.
• [56] A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2015 Apr 1;21(7):1566-73.
• [57] Clinical pipeline report, company report or official report of CytomX
• [58] Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. J Immunother Cancer. 2019 May 29;7(1):142.
• [59] ClinicalTrials.gov (NCT03638167) EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
• [60] World Antibody-Drug Conjugate Summit, October 15-16, 2013, San Francisco, CA. MAbs. 2014 January 1; 6(1): 18-29.
• [61] National Cancer Institute Drug Dictionary (drug id 596693).
• [62] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [63] Clinical pipeline report, company report or official report of Merus.
• [64] A Phase I Study of Immunotoxin, MR1-1. Duke University report.
• [65] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [66] Clinical pipeline report, company report or official report of SystImmune.
• [67] Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.Expert Opin Ther Pat. 2017 Dec;27(12):1305-1318.
• [68] Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats.J Pharmacol Exp Ther.2013 Jun;345(3):393-403.
• [69] GA201 (RG7160): a novel, humanized, glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab. Clin Cancer Res. 2013 Mar 1;19(5):1126-38.
• [70] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [71] EGFR tyrosine kinase inhibitor (PD153035) improves glucose tolerance and insulin action in high-fat diet-fed mice.Diabetes.2009 Dec;58(12):2910-9.
• [72] A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer. J Nucl Med. 2000 May;41(5):903-11.
• [73] Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
• [74] WO patent application no. 2009,0582,67, Benzomorpholine derivatives and methods of use.
• [75] Retinoic acid-induced RB (retinoblastoma) hypophosphorylation enhanced by CGP 52411 (4,5-dianilinophthalimide), an EGF family tyrosine kinase receptor inhibitor. Eur J Cell Biol. 1996 Apr;69(4):327-34.
• [76] Dianilinophthalimides: potent and selective, ATP-competitive inhibitors of the EGF-receptor protein tyrosine kinase. J Med Chem. 1994 Apr 1;37(7):1015-27.
• [77] The heparin-binding domain of heparin-binding EGF-like growth factor can target Pseudomonas exotoxin to kill cells exclusively through heparan sulfate proteoglycans. J Cell Sci. 1994 Sep;107 ( Pt 9):2599-608.
• [78] Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as poten... J Med Chem. 1995 Sep 1;38(18):3482-7.
• [79] Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase acti... J Med Chem. 1996 Feb 16;39(4):918-28.
• [80] 5-Benzylidene-hydantoins: synthesis and antiproliferative activity on A549 lung cancer cell line. Eur J Med Chem. 2009 Sep;44(9):3471-9.
• [81] Protein-tyrosine kinase inhibition: mechanism-based discovery of antitumor agents. J Nat Prod. 1992 Nov;55(11):1529-60.
• [82] Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species: novel inhibitors of protein kinases. J Nat Prod. 2000 Jun;63(6):739-45.
• [83] Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine... J Med Chem. 1991 Jun;34(6):1896-907.
• [84] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [85] Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: isoflavones and 3-phenyl-4(1H)-quinolones. J Med Chem. 1999 Mar 25;42(6):1018-26.
• [86] 5,7-Dimethoxy-3-(4-pyridinyl)quinoline is a potent and selective inhibitor of human vascular beta-type platelet-derived growth factor receptor tyro... J Med Chem. 1994 Aug 19;37(17):2627-9.
• [87] A novel series of 4-phenoxyquinolines: potent and highly selective inhibitors of PDGF receptor autophosphorylation, Bioorg. Med. Chem. Lett. 7(23):2935-2940 (1997).
• [88] Syntheses of 4-(indole-3-yl)quinazolines: a new class of epidermal growth factor receptor tyrosine kinase inhibitors. Eur J Med Chem. 2008 Jul;43(7):1478-88.
• [89] Acryloylamino-salicylanilides as EGFR PTK inhibitors. Bioorg Med Chem Lett. 2006 Jan 15;16(2):469-72.
• [90] Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: identification of new scaffolds for potent EGFR tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2007 Nov 1;17(21):5863-7.
• [91] Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorg Med Chem Lett. 2001 Jun 4;11(11):1401-5.
• [92] Computational studies of epidermal growth factor receptor: docking reliability, three-dimensional quantitative structure-activity relationship anal... J Med Chem. 2009 Feb 26;52(4):964-75.
• [93] Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6623-6.
• [94] Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors. J Med Chem. 1989 Oct;32(10):2344-52.
• [95] Cochliobolic acid, a novel metabolite produced by Cochliobolus lunatus, inhibits binding of TGF-alpha to the EGF receptor in a SPA assay. J Nat Prod. 1997 Jan;60(1):6-8.
• [96] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [97] Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85.
• [98] Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.
• [99] Novel antiproliferative agents derived from lavendustin A. J Med Chem. 1994 Nov 25;37(24):4079-84.
• [100] Effects of hEGF (MG111) on gastric mucosal potential difference in rats. Scand J Gastroenterol Suppl. 1989;162:198-201.
• [101] Synthesis of a prodrug designed to release multiple inhibitors of the epidermal growth factor receptor tyrosine kinase and an alkylating agent: a n... J Med Chem. 2003 Dec 4;46(25):5546-51.
• [102] Tyrosine kinase inhibitors. 10. Isomeric 4-[(3-bromophenyl)amino]pyrido[d]-pyrimidines are potent ATP binding site inhibitors of the tyrosine kinas... J Med Chem. 1996 Apr 26;39(9):1823-35.
• [103] Structure-guided development of affinity probes for tyrosine kinases using chemical genetics. Nat Chem Biol. 2007 Apr;3(4):229-38.
• [104] Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP... J Med Chem. 1999 May 20;42(10):1803-15.
• [105] Novel nitrogen mustard-armed combi-molecules for the selective targeting of epidermal growth factor receptor overexperessing solid tumors: discover... J Med Chem. 2007 May 31;50(11):2605-8.
• [106] The combi-targeting concept: synthesis of stable nitrosoureas designed to inhibit the epidermal growth factor receptor (EGFR). J Med Chem. 2006 Jun 15;49(12):3544-52.
• [107] Selected novel anticancer treatments targeting cell signaling proteins. Oncologist. 2001;6(6):517-37.
• [108] Growth factors and their receptors: new targets for prostate cancer therapy. Urology. 2001 Aug;58(2 Suppl 1):114-22.
• [109] Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor... J Med Chem. 2005 Feb 24;48(4):1107-31.
• [110] Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
• [111] Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem. 1996 Jan 5;39(1):267-76.
• [112] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [113] Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3.
• [114] The specificity of JAK3 kinase inhibitors. Blood. 2008 Feb 15;111(4):2155-7.
• [115] Clinical pipeline report, company report or official report of Biocytogen