The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
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
Open accessAbstract
4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), binding competitively at the ATP site. Structure-activity relationships for close analogues of 32 are very steep. Some derivatives have IC50s up to 80-fold better than predicted from simple additive binding energy arguments, yet analogues possessing combinations of similar phenyl and quinazoline substituents do not show this "supra-additive" effect. Because some substituents which are mildly deactivating by themselves can be strongly activating when used in the correct combinations, it is proposed that certain substituted analogues possess the ability to induce a change in the conformation of the receptor when they bind. There is some bulk tolerance for substitution in the 6- and 7-positions of the quinazoline, so that 32 is not the optimal inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3-bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 of 0.006 nM, making it the most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.
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Cites
The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains
Hanks, S. K., Quinn, A. M., & Hunter, T. (1988) · Science · doi:10.1126/science.3291115 · Cited by 5,039
Induction of Ectopic Eyes by Targeted Expression of the eyeless Gene in Drosophila
Halder, G., Callaerts, P., & Gehring, W. J. (1995) · Science · doi:10.1126/science.7892602 · Cited by 1,573
Structure of a human common cold virus and functional relationship to other picornaviruses
Rossmann, M. G., Arnold, E., Erickson, J. W., Frankenberger, E. A., Griffith, J. P., Hecht, H.-J., Johnson, J. E., Kamer, G., Luo, M., Mosser, A. G., et al. (1985) · Nature · doi:10.1038/317145a0 · Cited by 1,426
Crystal structure of the tyrosine kinase domain of the human insulin receptor
Hubbard, S. R., Wei, L., & Hendrickson, W. A. (1994) · Nature · doi:10.1038/372746a0 · Cited by 1,080
Atomic structure of the MAP kinase ERK2 at 2.3 A resolution
Zhang, F., Strand, A., Robbins, D., Cobb, M. H., & Goldsmith, E. J. (1994) · Nature · doi:10.1038/367704a0 · Cited by 592
Zheng, J., Knighton, D. R., Ten Eyck, L. F., Karlsson, R., Xuong, N., Taylor, S. S., & Sowadski, J. M. (1993) · Biochemistry · doi:10.1021/bi00060a005 · Cited by 589
Bossemeyer, D., Engh, R. A., Kinzel, V., Ponstingl, H., & Huber, R. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05725.x · Cited by 389
Fc Receptors Initiate the Arthus Reaction: Redefining the Inflammatory Cascade
Sylvestre, D. L., & Ravetch, J. V. (1994) · Science · doi:10.1126/science.8066448 · Cited by 321
Rewcastle, G. W., Denny, W. A., Bridges, A. J., Zhou, H., Cody, D. R., McMichael, A., & Fry, D. W. (1995) · Journal of Medicinal Chemistry · doi:10.1021/jm00018a008 · Cited by 263
Self-citationHickey, K., Grehan, D., Reid, L. M., O’Briain, S., Walsh, T. N., & Hennessy, T. P. J. (1994) · Cancer · doi:10.1002/1097-0142(19940915)74:6<1693::aid-cncr2820740609>3.0.co;2-# · Cited by 117
Takase, Y., Saeki, T., Watanabe, N., Adachi, H., Souda, S., & Saito, I. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00039a024 · Cited by 103
Traxler, P. M., Wacker, O., Bach, H., Geissler, J. F., Kump, W. G., Meyer, T., Regenass, U., Roesel, J. L., & Lydon, N. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00112a003 · Cited by 57
A convective model for the zonal jets in the atmospheres of Jupiter and Saturn
Condie, S. A., & Rhines, P. B. (1994) · Nature · doi:10.1038/367711a0 · Cited by 49
[8] In Vitro growth of A431 human epidermoid carcinoma
Barnes, D. W. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(87)46011-4 · Cited by 11
Air Force Determines Potential Cause of Titan Rocket Explosion
Smith, R. J. (1986) · Science · doi:10.1126/science.233.4761.278.b · Cited by 11
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Sun, L., Tran, N., Tang, F., App, H., Hirth, P., McMahon, G., & Tang, C. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm980123i · Cited by 489
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AL Zahrani, N. A., El-Shishtawy, R. M., & Asiri, A. M. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112609 · Cited by 346
Chemical Inhibitors of Protein Kinases
Bridges, A. J. (2001) · Chemical Reviews · doi:10.1021/cr000250y · Cited by 320
Self-citationSmaill, J. B., Rewcastle, G. W., Loo, J. A., Greis, K. D., Chan, O. H., Reyner, E. L., Lipka, E., Showalter, H. D. H., Vincent, P. W., Elliott, W. L., et al. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990482t · Cited by 269
Self-citationGrowth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes
Smith, G. M., & Strunz, C. (2005) · Glia · doi:10.1002/glia.20236 · Cited by 174
Metadata
- Authors
- Bridges, A. J., Zhou, H., Cody, D. R., Rewcastle, G. W., McMichael, A., Showalter, H. D. H., Fry, D. W., Kraker, A. J., & Denny, W. A.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1996-01-01
- Volume
- 39
- Issue
- 1
- Pages
- 267-276
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2066498455
- Cited by
- 320
- References
- 15
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- green
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