The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
A Specific Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase
Abstract
A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Four synthesized derivatives of 6- or 7-acrylamide-4-anilino-quinazolines, PD 160678 (70), PD 168393 (71), PD 160879 (72), PD 174265 (73), irreversibly inhibit EGFR TK activity with IC50 values 0.45–0.70 nM.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [204]
Citations
Cites
Oncogenes and signal transduction
Cantley, L. C., Auger, K. R., Carpenter, C. F., Duckworth, B. C., Graziani, A., Kapeller, R., & Soltoff, S. P. (1991) · Cell · doi:10.1016/0092-8674(91)90639-g · Cited by 2,697
Aaronson, S. A. (1991) · Science · doi:10.1126/science.1659742 · Cited by 2,017
Growth factor signaling by receptor tyrosine kinases
Schlessinger, J., & Ullrich, A. (1992) · Neuron · doi:10.1016/0896-6273(92)90177-f · Cited by 1,418
RECEPTORS FOR EPIDERMAL GROWTH FACTOR AND OTHER POLYPEPTIDE MITOGENS
Carpenter, G. F. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.004313 · Cited by 1,282
Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors
Morrison, J. F. (1969) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(69)90420-3 · Cited by 815
Sandgren, E. P., Luetteke, N., Palmiter, R. D., Brinster, R. L., & Lee, D. C. (1990) · Cell · doi:10.1016/0092-8674(90)90075-p · Cited by 752
Jhappan, C., Stahle, C., Harkins, R. N., Fausto, N., Smith, G. H., & Merlino, G. T. (1990) · Cell · doi:10.1016/0092-8674(90)90076-q · Cited by 709
Clark, A. N. G., Mankikar, G. D., & Gray, I. (1975) · The Lancet · doi:10.1016/s0140-6736(75)91280-5 · Cited by 697
Neal, D. E., Bennett, M., Hall, R. R., Marsh, C., Abel, P., Sainsbury, J. R. C., & Harris, A. L. (1985) · The Lancet · doi:10.1016/s0140-6736(85)91386-8 · Cited by 604
Masui, H., Kawamoto, T., Sato, J., Wolf, B., SATO, G. H., & Mendelsohn, J. M. (1984) · The Journal of Urology · doi:10.1016/s0022-5347(17)50005-1 · Cited by 446
Flagged first, then by citations
Research works printed but not linked: 1
- HENDLER, F. J., Increased EGF-R1 binding predicts a poor survival in squamous tumors, CANCER CELLS 7: 347 (1989).
Cited by
Sorted by citations
Items 701–800 of 830
Portilla, J., Jairo Quiroga, P., Cobo, J., Nogueras, M., Low, J. N., & Glidewell, C. (2005) · Acta Crystallographica Section C Crystal Structure Communications · doi:10.1107/s0108270105013260 · Cited by 2
Receptor Tyrosine Kinases as Targets for Cancer Therapy Development
Gschwind, A., Fischer, O. M., & Ullrich, A. (2006) · Springer eBooks · doi:10.1007/3-540-34447-0_11 · Cited by 2
Lluria-Prevatt, M., & Alberts, D. S. (2005) · Springer eBooks · doi:10.1007/3-540-26337-3_9 · Cited by 2
The Changing Face of Innovation in Drug Discovery
Zhang, L., & Decicco, C. P. (2014) · Wiley eBooks · doi:10.1002/9781118778166.ch4 · Cited by 2
Solid-phase synthesis of 2,4-diaminoquinazolines
Wu, Z., Kim, J., Söll, R., & Dhanoa, D. S. (2000) · Biotechnology and Bioengineering · doi:10.1002/1097-0290(200021)71:2 · Cited by 2
Emerging Molecular Therapies: Small-Molecule Drugs
Workman, P. (2003) · Humana Press eBooks · doi:10.1385/1-59259-222-8:421 · Cited by 2
Adams, J. L., Veal, J. M., & Shewchuk, L. M. (2008) · Protein Science Encyclopedia · doi:10.1002/9783527610754.pl04 · Cited by 2
Mehta, R. K., Tan, M., Hassan, M. K., Zhao, T., Markovitz, D. M., Lawrence, T. S., & Nyati, M. K. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150711 · Cited by 1
Lee, H. E., Kim, M. G., & Jeon, B. (2025) · Archives of Pharmacal Research · doi:10.1007/s12272-025-01582-w · Cited by 1
Junaid, M., Gautham, S. K., Bhoomandla, S., & Nune, S. V. K. (2026) · Letters in Organic Chemistry · doi:10.2174/0115701786430284251214170953 · Cited by 1
Chen, Y., Liu, Q.-P., Yang, S.-J., Ding, J., Lu, X.-Y., & Xie, H. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-026-01855-0 · Cited by 1
A theoretical study on basicity behaviour of some 4-aminoquinazoline derivatives
Tay, F., & Arslan, T. (2011) · DergiPark (Istanbul University) · doi:10.20290/btdb.07240 · Cited by 1
Mortlock, A. A., & Barker, A. J. (2007) · Elsevier eBooks · doi:10.1016/b0-08-045044-x/00209-1 · Cited by 1
Al-Sehemi, A. G., Al-Amri, R. S. A. A., & Irfan, A. (2013) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2013.07.011 · Cited by 1
Cooper, M. A., & Caligiuri, M. A. (2003) · Elsevier eBooks · doi:10.1016/b978-012689663-3/50057-0 · Cited by 1
In Silico Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors
Fernandes, G. S., Pereira, M. B. D. M., Marinho, A. C. B., Machado, B., Moreira, A. C., Freitas, M. P., Lang, K. L., & Antunes, J. E. (2015) · Open Journal of Medicinal Chemistry · doi:10.4236/ojmc.2015.54007 · Cited by 1
Timaniya, J. B., Parikh, P. H., Patel, M. J., & Patel, K. P. (2023) · Results in Chemistry · doi:10.1016/j.rechem.2023.101225 · Cited by 1
Recent Application of Polystyrene-supported Triphenylphosphine in Solid-Phase Organic Synthesis
Rokhum, S. L., & Bez, G. (2018) · Current Organic Chemistry · doi:10.2174/1385272822666181026115752 · Cited by 1
Mphahlele, M. J., Maluleka, M. M., & Mmonwa, M. M. (2019) · Springer eBooks · doi:10.1007/978-3-030-20283-5_18 · Cited by 1
One-pot Three-component Synthesis of Novel Quinazoline-4-carboxylic Acid and Derivatives
Gök, D. (2020) · Hacettepe Journal of Biology and Chemistry · doi:10.15671/hjbc.736847 · Cited by 1
Case Study on Receptor Tyrosine Kinases EGFR, VEGFR, and PDGFR
Lima, L. M., Barbosa, M. L. D. C., do Amaral, D. N., & Barreiro, E. J. (2020) · Topics in medicinal chemistry · doi:10.1007/7355_2020_95 · Cited by 1
Syntheses and molecular structures of some di(amidino)monosilanes
Bös, M., Herbig, M., Böhme, U., & Kroke, E. (2021) · Main Group Metal Chemistry · doi:10.1515/mgmc-2021-0024 · Cited by 1
(1995) · Annals of the Rheumatic Diseases · doi:10.1136/ard.54.6.501-a · Cited by 1
Alves, F., & Hiddemann, W. (1997) · Der Internist · doi:10.1007/s001080050120 · Cited by 1
Tykerb Discovery: A Dual EGFR and ERBB2 Tyrosine Kinase Inhibitor
Lackey, K. E., & Cockerill, G. S. (2009) · doi:10.1002/9780470524961.ch2 · Cited by 1
Lluria-Prevatt, M., Dickinson, S. E., & Alberts, D. S. (2013) · Springer eBooks · doi:10.1007/978-3-642-38983-2_12 · Cited by 1
Bannwarth, W. (2000) · Methods and principles in medicinal chemistry · doi:10.1002/9783527614141.ch03 · Cited by 1
Sizemore, N., Wright, D. S., Mueller, W. T., & Kuo, B. (1996) · Peptides · doi:10.1016/s0196-9781(96)00191-x · Cited by 1
Two quinazolinones: a ring conformational study
Swamy, G. Y. S. K., Sridhar, B., Ravikumar, K., & SADANANDAM, Y. S. (2008) · Acta Crystallographica Section C Crystal Structure Communications · doi:10.1107/s0108270107068850 · Cited by 1
Insulin reduces the requirement for EGFR transactivation in bombesin-induced DNA synthesis
Santiskulvong, C., Sinnett‐Smith, J. W., & Rozengurt, E. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.04.100 · Cited by 1
Studies on the Differential Specificity of Protein Kinases and Its Applications
Loog, M. (2001) · Cited by 1
Engineering Protein Kinases with Specificity for Unnatural Nucleotides and Inhibitors
Zhang, C., & Shokat, K. M. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00081-4 · Cited by 1
Gee, J., & Nicholson, R. (2002) · CRC Press eBooks · doi:10.1201/b14039-12
Haas-Kogan, D. A., & Frisch, B. M. (2004) · Pediatric oncology · doi:10.1007/978-3-662-09227-9_16 · Cited by 1
Workman, P. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-222-7_17 · Cited by 1
Hagmann, W., & Borgers, S. (1997) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-1813-0_2
Targeting Oncogenic Signaling Pathways in Human Astrocytomas
Zadeh, G. M., & Guha, A. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-313-2_18
Combinations of Cytotoxic Drugs, Ionizing Radiation and EGFR Inhibitors
Lammering, G. (2006) · Springer eBooks · doi:10.1007/3-540-35662-2_8
Screening of peptidomimetic tyrosine kinase inhibitors for inducing programmed cell death
Kéri, G., Őrfi, L., Hollósy, F., Vántus, T., Érchegyi, J., Idei, M., Horváth, A., Teplán, I., Gazit, A., Peták, I., et al. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46864-6_12
Discovery of small molecule insulin mimetics as potential novel antidiabetic agents
Zhang, B. B. (2002) · Pharmacochemistry library · doi:10.1016/s0165-7208(02)80023-x
Tyrphostin AG 1478 Accelerates Hydrogen Peroxide-Induced Apoptosis in A431 Cells
Tsukada, T., Ida, H., Kawakami, A., Eguchi, K., & Harris, R. C. (2003) · Institutional Repositories DataBase (IRDB)
Lapatinib, an Anticancer Kinase Inhibitor
Lackey, K. E. (2010) · doi:10.1002/9783527630035.ch19
Sheng, J., Zhang, M., Lu, L., & Wang, X. (2012) · Journal of Chemical Crystallography · doi:10.1007/s10870-012-0303-z
Crystal Structure of 2-(4-Chlorophenyl)-1-phenethyl-2,3-dihydro-4(1H)-quinazolinone
Swamy, G. Y. S. K., & Ravikumar, K. (2006) · X-ray Structure Analysis Online · doi:10.2116/analscix.22.x71
Optimization of the Development of Old and New EGFR and MAP Kinase Inhibitors for Colorectal Cancer
Martinelli, E., Napolitano, S., Ciardiello, D., Ciardiello, F., & Troiani, T. (2014) · Current Colorectal Cancer Reports · doi:10.1007/s11888-014-0233-6
Patent focus: inhibitors of tumour cell growth
Kath, J. C. (2000) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.10.6.803
Bowden, G. T., & Alberts, D. S. (2010) · Springer eBooks · doi:10.1007/978-1-4419-7203-3_16
Transcriptional regulation by v-ErbA, the oncogenic counterpart of thyroid hormone receptor (TR)
Braliou, G. G. (2000) · Radboud Repository (Radboud University)
The Potential of Tyrphostins for the Therapy of Breast Cancer
Levitzki, A., & Gazit, A. (2000) · Breast Disease · doi:10.3233/bd-1999-11113
International Journal for Pharmaceutical Research Scholars (IJPRS)
Sp, T., Pk, T., Ph, J., & Gv, P. (2014)
Drug Discovery Approaches Targeting the JAK/STAT Pathway
Seidel, H. M., & Rosen, J. (2003) · Springer eBooks · doi:10.1007/978-94-017-3000-6_45
GROWTH FACTOR AND SIGNAL TRANSDUCTION TARGETS FOR CANCER THERAPY
Leopold, W. R., Bridges, A. J., Decker, S. J., Fry, D. W., Kraker, A. J., & Sebolt, J. S. (2002) · Elsevier eBooks · doi:10.1016/b978-012072651-6/50004-8
Self-citationWadhwani, A. (2013) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/26622
Ren, Z., & Baumgarten, C. M. (2016)
Haas-Kogan, D. A., & McBride, S. M. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-5897-7.00073-1
Lipson, K. E., Sun, L., Liang, C., & McMahon, G. (2000) · CRC Press eBooks · doi:10.1201/9780203904244.ch11
Drug discovery and cancer genetics
Crompton, M. R. (1996) · Springer eBooks · doi:10.1007/978-1-4899-3111-5_19
Future prospects for the endocrine management of breast cancer
Gee, J. M. W. (2002) · CRC Press eBooks · doi:10.1201/b14733-19
Tyr Kinase Inhibitors as Potential Anticancer Agents
Burgess, A. W. (2002) · Elsevier eBooks · doi:10.1016/b978-012476249-7/50018-7
Engineering Protein Kinases with Specificity for Unnatural Nucleotides and Inhibitors
Zhang, C., & Shokat, K. M. (2003) · Elsevier eBooks · doi:10.1016/b978-012124546-7/50459-9
Mc, C., Pirro, N. T., Ac, M., Ea, T., & Pe, G. (2020) · Journal of Cell Signaling · doi:10.35248/2576-1471.20.5.204
Modulation of Kinases by Small Molecules for Therapeutic Management of Various Diseases - Part I
Bharate, S. B. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/156802662012200504090532
Investigating the Maintenance of Desmoid Tumors beyond Beta-catenin
Al‐Jazrawe, M. (2019) · TSpace (University of Toronto)
Reilly, R. M. (1999) · Library and Archives Canada (Government of Canada)
Meek, T. D. (2021) · Wiley eBooks · doi:10.1002/0471266949.bmc260
Chédotal, A., & Blockus, H. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718011102.793476889
4-Anilinoquinazoline derivatives
(1998) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.8.4.475
Automatisierung in den Lebenswissenschaften – eine kritische Betrachtung
Fleischer, H., & Thurow, K. (2019) · doi:10.1002/9783527822843.ch2
Automation in Life Sciences – A Critical Review
Fleischer, H., & Thurow, K. (2017) · doi:10.1002/9783527805297.ch2
Nantermet, P. G., Shalen, E. F., Venkatraman, S., Zhu, H., & Mark, R. J. (2010) · Burger's Medicinal Chemistry and Drug Discovery · doi:10.1002/0471266949.bmc250
The pathogenesis of cancer metastasis: relevance to biotherapy
Radinsky, R., Aukerman, S. L., & Fidler, I. J. (2003) · Springer eBooks · doi:10.1007/978-94-017-2757-0_2
Sowadski, J. M., & Epstein, L. F. (2001) · Encyclopedia of Life Sciences · doi:10.1038/npg.els.0000659
Todd, A., Groundwater, P. W., & Gill, J. H. (2017) · doi:10.1002/9781118696194.ch2.5
Chapter 4 convergent assembly strategies on solid supports
(1998) · Tetrahedron organic chemistry/Tetrahedron organic chemistry series · doi:10.1016/s1460-1567(98)80031-7
Nassari, S., Blavet, C., Duprez, D., & Fournier‐Thibault, C. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.08.499311
Sireci, S., Kocagöz, Y., Alkiraz, A. S., Güler, K., Dokuzluoglu, Z., Balcioglu, E., Demirler, M. C., & Fuss, S. H. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.26.509477
Gök, D. (2022) · Hacettepe Journal of Biology and Chemistry · doi:10.15671/hjbc.1004758
Deeb, O., Muhtaseb, M., & Shaik, B. (2024) · British Journal of Multidisciplinary and Advanced Studies · doi:10.37745/bjmas.2022.0455
Cyclin-Dependent Kinases and Their Regulators as Potential Targets for Anticancer Therapeutics
Brizuela, L., Gyuris, J., & Mansuri, M. M. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-222-7_8 · Cited by 2
Protein Tyrosine Kinase Inhibitors as Novel Therapeutic Agents
Levitzki, A. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-218-0_25
High-throughput screening and rational drug design
Singh, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-27461-9.00013-5
USO DA BIOINFORMÁTICA PARA SELECIONAR MOLÉCULAS CANDIDATAS A FÁRMACOS
Costa, J. B., Santos, T. S. D., Franconi, L., Sathler, A. D. A., Pereira, M. B. D. M., & Antunes, J. E. (2025) · LUMEN ET VIRTUS · doi:10.56238/levv16n53-039
The Biology of Liver Metastasis
Radinsky, R., & Fidler, I. J. (1998) · Springer eBooks · doi:10.1007/978-1-4471-1506-9_3
XIIth international symposium on radiopharmaceutical chemistry: Abstracts and programme
(1997) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.2580400501
Jain, N., & Iwaoka, M. (2026) · Frontiers in Chemistry · doi:10.3389/fchem.2026.1768658
Base-Free C–N Cross-Electrophile Coupling
Samanta, S., Patel, L., Manna, D., Ojeda, M., & Powers, D. C. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c05089
Alsfouk, A. A., Othman, I. M. M., Alzahrani, A. Y. A., Saleh, A., & Nossier, E. S. (2026) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2026.147719
Hartung, F., Reichert, D., Hacheney, I., Rossi, A., & Haarmann‐Stemmann, T. (2026) · Archives of Toxicology · doi:10.1007/s00204-026-04574-x
Metadata
- Authors
- Fry, D. W., Kraker, A. J., McMichael, A., Ambroso, L. A., Nelson, J. M., Leopold, W. R., Connors, R. W., & Bridges, A. J.
- Affiliations
- Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105.
- ORCID
- Nelson, James M.
- Venue
- Science
- Published
- 1994-08-19
- Volume
- 265
- Issue
- 5175
- Pages
- 1093-1095
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2069637592
- Cited by
- 806
- References
- 28
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 10 · 2021: 12 · 2020: 19 · 2019: 11 · 2018: 13 · 2017: 18 · 2016: 13 · 2015: 18 · 2014: 24 · 2013: 26 · 2012: 31
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- epidermal growth factor receptor, tyrosine kinase inhibitors, receptor autophosphorylation, mitogenesis, oncogenic transformation, early gene expression, small molecule inhibitors, kinase specificity
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Epidermal Growth Factor, Humans, Kinetics, Mitosis, Phosphorylation, Platelet-Derived Growth Factor, Protein-Tyrosine Kinases, Quinazolines, Tumor Cells, Cultured, Tyrosine, Gene Expression, Fibroblast Growth Factor 2, 3T3 Cells, Mice, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review