A credit-card library approach for disrupting protein–protein interactions
Abstract
Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in human cancers. Myc belongs to the family of basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factors. It is biologically active only as heterodimer with the bHLH-ZIP protein Max. Herein, we report a new strategy for the disruption of protein-protein interactions that has been corroborated through the design and synthesis of a small parallel library composed of 'credit-card' compounds. These compounds are derived from a planar, aromatic scaffold and functionalized with four points of diversity. From a 285 membered library, several hits were obtained that disrupted the c-Myc-Max interaction and cellular functions of c-Myc. The IC50 values determined for this small focused library for the disruption of Myc-Max dimerization are quite potent, especially since small molecule antagonists of protein-protein interactions are notoriously difficult to find. Furthermore, several of the compounds were active at the cellular level as shown by their biological effects on Myc action in chicken embryo fibroblast assays. In light of our findings, this approach is considered a valuable addition to the armamentarium of new molecules being developed to interact with protein-protein interfaces. Finally, this strategy for disrupting protein-protein interactions should prove applicable to other families of proteins.
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Functional organization of the yeast proteome by systematic analysis of protein complexes
Gavin, A., Böesche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A., Cruciat, C., et al. (2002) · Nature · doi:10.1038/415141a · Cited by 4,729 · see citing works
Multicomponent Reactions with Isocyanides
Dömling, A. S. S., & Ugi, I. (2000) · Angewandte Chemie International Edition · doi:10.1002/1521-3773(20000915)39:18 · Cited by 4,079 · see citing works
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry
Ho, Y., Gruhler, A., Heilbut, A. M., Bader, G. D., Moore, L., Adams, S., Millar, A., Taylor, P. P., Bennett, K. L., Boutilier, K., et al. (2002) · Nature · doi:10.1038/415180a · Cited by 3,573 · see citing works
Principles of protein-protein interactions
Jones, S., & Thornton, J. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.1.13 · Cited by 2,684 · see citing works
Anatomy of hot spots in protein interfaces
Bogan, A. A., & Thorn, K. S. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1843 · Cited by 1,988 · see citing works
The atomic structure of protein-protein recognition sites 1 1Edited by A. R. Fersht
Conte, L. L., Chothia, C., & Janin, J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2439 · Cited by 1,967 · see citing works
Small-molecule inhibitors of protein–protein interactions: progressing towards the dream
Arkin, M. R., & Wells, J. A. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1343 · Cited by 1,705 · see citing works
Max: A Helix-Loop-Helix Zipper Protein That Forms a Sequence-Specific DNA-Binding Complex with Myc
Blackwood, E. M., & Eisenman, R. N. (1991) · Science · doi:10.1126/science.2006410 · Cited by 1,681 · see citing works
A Planning Strategy for Diversity‐Oriented Synthesis
Burke, M. D., & Schreiber, S. L. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200300626 · Cited by 1,493 · see citing works
Shape Complementarity at Protein/Protein Interfaces
Lawrence, M. C., & Colman, P. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1648 · Cited by 1,219 · see citing works
Shape complementarity at protein–protein interfaces
Norel, R., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1994) · Biopolymers · doi:10.1002/bip.360340711 · Cited by 1,208 · see citing works
Gallop, M. A., Barrett, R. W., Dower, W. J., Fodor, S. P. A., & Gordon, E. M. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00035a001 · Cited by 1,135 · see citing works
Unraveling hot spots in binding interfaces: progress and challenges
DeLano, W. L. (2002) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00283-x · Cited by 767 · see citing works
A natural classification of the basic helix–loop–helix class of transcription factors
Atchley, W. R., & Fitch, W. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5172 · Cited by 686 · see citing works
Combinatorial synthesis — the design of compound libraries and their application to drug discovery
Terrett, N. K., Gardner, M., Gordon, D. W., Kobylecki, R. J., & Steele, J. (1995) · Tetrahedron · doi:10.1016/0040-4020(95)00467-m · Cited by 660 · see citing works
A Small Molecule Smac Mimic Potentiates TRAIL- and TNFα-Mediated Cell Death
Li, L., Thomas, R., Suzuki, H., Brabander, J. D., Wang, X.-D., & Harran, P. G. (2004) · Science · doi:10.1126/science.1098231 · Cited by 620 · see citing works
Multicomponent one-pot annulations forming 3 to 6 bonds
Posner, G. H. (1986) · Chemical Reviews · doi:10.1021/cr00075a007 · Cited by 581 · see citing works
Oncogenic activity of the c-Myc protein requires dimerization with Max
Amati, B. B., Brooks, M. W., Levy-Strumpf, N., Littlewood, T. D., Evan, G. I., & Land, H. (1993) · Cell · doi:10.1016/0092-8674(93)90663-b · Cited by 559 · see citing works
Protein−Protein Interactions: Interface Structure, Binding Thermodynamics, and Mutational Analysis
Stites, W. E. (1997) · Chemical Reviews · doi:10.1021/cr960387h · Cited by 491 · see citing works
Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
Bowman, T., Broome, M. A., Sinibaldi, D., Wharton, W., Pledger, W. J., Sedivy, J. M., Irby, R., Yeatman, T., Courtneidge, S. A., & Jove, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131568898 · Cited by 488 · see citing works
A general and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives
Bunin, B. A., & Ellman, J. A. (1992) · Journal of the American Chemical Society · doi:10.1021/ja00053a067 · Cited by 443 · see citing works
Low molecular weight inhibitors of Myc–Max interaction and function
Yin, X., Giap, C., Lazo, J. S., & Prochownik, E. V. (2003) · Oncogene · doi:10.1038/sj.onc.1206641 · Cited by 426 · see citing works
Myc and Max associate in vivo.Preprint
Blackwood, E. M., Lüscher, B., & Eisenman, R. N. (1992) · Genes & Development · doi:10.1101/gad.6.1.71 · Cited by 415 · see citing works
The c‐Myc protein induces cell cycle progression and apoptosis through dimerization with Max.
Amati, B. B., Littlewood, T. D., Evan, G. I., & Land, H. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06202.x · Cited by 384 · see citing works
Function of the c-Myc Oncogenic Transcription Factor
Dang, C. V., Resar, L. M. S., Emison, E. S., Kim, S., Li, Q., Prescott, J. E., Wonsey, D. R., & Zeller, K. I. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4686 · Cited by 377 · see citing works
Binding of small molecules to an adaptive protein–protein interface
Arkin, M. R., Randal, M., DeLano, W. L., Hyde, J., Luong, T. N., Oslob, J. D., Raphael, D. R., Taylor, L., Wang, J., McDowell, R. S., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252756299 · Cited by 376 · see citing works
"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity.
DeWitt, S. H., Kiely, J. S., Stankovic, C. J., Schroeder, M. C., Cody, D. M., & Pavia, M. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.15.6909 · Cited by 340 · see citing works
Berg, T., Cohen, S. B., Desharnais, J., Sonderegger, C. K., Maslyar, D. J., Goldberg, J., Boger, D. L., & Vogt, P. K. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062036999 · Cited by 326 · see citing works
Self-citationProtein flexibility and drug design: how to hit a moving target
Carlson, H. A. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00341-1 · Cited by 314 · see citing works
Modulation of Protein–Protein Interactions with Small Organic Molecules
Berg, T. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200200558 · Cited by 292 · see citing works
BiGGER: A new (soft) docking algorithm for predicting protein interactions
Palma, P. N., Krippahl, L., Wampler, J. E., & Moura, J. J. G. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(20000601)39:4 · Cited by 292 · see citing works
Ugi, I. (1962) · Angewandte Chemie · doi:10.1002/ange.19620740103 · Cited by 266 · see citing works
Antagonists of protein–protein interactions
Cochran, A. G. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00106-x · Cited by 228 · see citing works
Dang, C. V., McGuire, M., Buckmire, M., & Lee, W. M. F. (1989) · Nature · doi:10.1038/337664a0 · Cited by 193 · see citing works
Boger, D. L., Desharnais, J., & Capps, K. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200300574 · Cited by 171 · see citing works
Small Molecule Affinity Fingerprinting
Greenbaum, D. C., Arnold, W. D., Lu, F., Hayrapetian, L., Baruch, A., Krumrine, J. R., Toba, S., Chehade, K. A. H., Brömme, D., Kuntz, I. D., et al. (2002) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00238-7 · Cited by 168 · see citing works
Spring, D. R., Krishnan, S., Blackwell, H. E., & Schreiber, S. L. (2002) · Journal of the American Chemical Society · doi:10.1021/ja017248o · Cited by 165 · see citing works
The RNA of avian acute leukemia virus MC29.
DUESBERG, P. H., Bister, K., & Vogt, P. K. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.10.4320 · Cited by 157 · see citing works
Self-citationNeue Darstellungsmethode für Isonitrile
Ugi, I., & Meyr, R. (1958) · Angewandte Chemie · doi:10.1002/ange.19580702213 · Cited by 151 · see citing works
Sternson, S. M., Wong, J. C., Grozinger, C. M., & Schreiber, S. L. (2001) · Organic Letters · doi:10.1021/ol016915f · Cited by 139 · see citing works
Harrison, S. C., Ferrer, M., Kapoor, T. M., Strassmaier, T., Weissenhorn, W., Skehel, J. J., Oprian, D., Schreiber, S. L., & Wiley, D. C. (1999) · Nature Structural Biology · doi:10.1038/13324 · Cited by 138 · see citing works
Parniak, M. A., Min, K., Budihas, S. R., Grice, S. F. J. L., & Beutler, J. A. (2003) · Analytical Biochemistry · doi:10.1016/j.ab.2003.06.001 · Cited by 127 · see citing works
c-MYC apoptotic function is mediated by NRF-1 target genesPreprint
Morrish, F. M., Giedt, C. D., & Hockenbery, D. M. (2003) · Genes & Development · doi:10.1101/gad.1032503 · Cited by 123 · see citing works
The generation of molecular diversity
Pavia, M. R., Sawyer, T. K., & Moos, W. H. (1993) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)80220-1 · Cited by 115 · see citing works
Protein functional epitopes: hot spots, dynamics and combinatorial libraries
Ma, B., Wolfson, H. J., & Nussinov, R. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(00)00216-5 · Cited by 111 · see citing works
DUESBERG, P. H., & Vogt, P. K. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.4.1633 · Cited by 110 · see citing works
Self-citationLavigne, P., Kondejewski, L. H., Houston, M. E., Jr., Sönnichsen, F. D., Lix, B., Sykes, B. D., Hodges, R. S., & Kay, C. M. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0634 · Cited by 109 · see citing works
Lavigne, P., Crump, M. P., Gagné, S. M., Hodges, R. S., Kay, C. M., & Sykes, B. D. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.1914 · Cited by 109 · see citing works
Janda, K. D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10779 · Cited by 106 · see citing works
Self-citationProtein–protein interactions: mechanisms and modification by drugs
Veselovsky, A. V., Ivanov, Y. D., Ivanov, A. S., Archakov, A. I., Lewi, P. J., & Janssen, P. (2002) · Journal of Molecular Recognition · doi:10.1002/jmr.597 · Cited by 102 · see citing works
High Throughput Screening via Mass Spectrometry: A Case Study Using Acetylcholinesterase
Özbal, C. C., LaMarr, W. A., Linton, J. R., Green, D. F., Katz, A., Morrison, T. B., & Brenan, C. J. H. (2004) · Assay and Drug Development Technologies · doi:10.1089/adt.2004.2.373 · Cited by 81 · see citing works
Regulation of both apoptosis and cell survival by the v-Src oncoprotein
Johnson, D., Agochiya, M., Samejima, K., Earnshaw, W. C., Frame, M. C., & Wyke, J. A. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400700 · Cited by 78 · see citing works
Myc/Max and other helix-loop-helix/leucine zipper proteins bend DNA toward the minor groove.
Fisher, D. E., Parent, L. A., & Sharp, P. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.24.11779 · Cited by 77 · see citing works
Taylor, S. J., Taylor, A. M., & Schreiber, S. L. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200353466 · Cited by 76 · see citing works
Cheng, S., Tarby, C. M., Comer, D. D., Williams, J. P., Caporale, L. H., Myers, P. L., & Boger, D. L. (1996) · Bioorganic & Medicinal Chemistry · doi:10.1016/0968-0896(96)00069-7 · Cited by 74 · see citing works
Pearce, K. H., Ultsch, M. H., Kelley, R. F., de Vos, A. M., & Wells, J. A. (1996) · Biochemistry · doi:10.1021/bi960513b · Cited by 73 · see citing works
Identification of Potent Ras Signaling Inhibitors by Pathway‐Selective Phenotype‐Based Screening
Müller, O., Gourzoulidou, E., Carpintero, M., Karaguni, I., Langerak, A., Herrmann, C., Möröy, T., Klein‐Hitpaß, L., & Waldmann, H. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200352587 · Cited by 70 · see citing works
Genetic dissection of c-myc apoptotic pathways
Nesbit, C. E., Tersak, J. M., Grove, L. E., Drzal, A., Choi, H.-J., & Prochownik, E. V. (2000) · Oncogene · doi:10.1038/sj.onc.1203636 · Cited by 58 · see citing works
The Myc:Max Protein Complex and Cell Growth RegulationPreprint
Blackwood, E. M., Lüscher, B., Kretzner, L., & Eisenman, R. N. (1991) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1991.056.01.015 · Cited by 49 · see citing works
Davis, L. J., & Halazonetis, T. D. (1993) · PubMed · Cited by 36 · see citing works
Role of Oncogenic Transcription Factor c-Myc in Cell Cycle Regulation, Apoptosis and Metabolism
Dang, C. V., & Lewis, B. C. (1997) · Journal of Biomedical Science · doi:10.1007/bf02258350 · Cited by 35 · see citing works
Kolasa, T., Gunn, D., Bhatia, P. A., Basha, A., Craig, R. A., Stewart, A. O., Bouska, J. B., Harris, R. R., Hulkower, K. I., Malo, P. E., et al. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000180n · Cited by 29 · see citing works
Cheon, H., Lee, C., Kim, B., & Hwang, K. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.02.065 · Cited by 16 · see citing works
Purification Strategies for Combinatorial and Parallel Chemistry
Edwards, P. J. (2003) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207033329832 · Cited by 15 · see citing works
Combinatorial Approaches in Anticancer Drug Discovery: Recent Advances in Design and Synthesis
Bhattacharyya, S. (2001) · Current Medicinal Chemistry · doi:10.2174/0929867013372139 · Cited by 12 · see citing works
Design of screening libraries biased for pharmaceutical discovery
Koehler, R. T., & Villar, H. O. (2000) · Journal of Computational Chemistry · doi:10.1002/1096-987x(200010)21:13 · Cited by 8 · see citing works
Berg, T. (2004) · ChemBioChem · doi:10.1002/cbic.200400054 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 68 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Understanding protein non-folding
Uversky, V. N., & Dunker, A. K. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.01.017 · Cited by 1,188 · see citing works
The Myc oncoprotein as a therapeutic target for human cancer
Vita, M. F., & Arsenian‐Henriksson, M. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.07.015 · Cited by 554 · see citing works
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497 · see citing works
Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy
Han, H., Jain, A. D., Truica, M. I., Izquierdo-Ferrer, J., Anker, J. F., Lysy, B., Sagar, V., Luan, Y., Chalmers, Z. R., Unno, K., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.001 · Cited by 461 · see citing works
Taking the Myc out of cancer: toward therapeutic strategies to directly inhibit c-Myc
Madden, S. K., de Araujo, A. D., Gerhardt, M., Fairlie, D. P., & Mason, J. M. (2021) · Molecular Cancer · doi:10.1186/s12943-020-01291-6 · Cited by 404 · see citing works
Intrinsically disordered proteins are potential drug targets
Metallo, S. J. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.06.169 · Cited by 298 · see citing works
Strategies to Inhibit Myc and Their Clinical Applicability
Whitfield, J. R., Beaulieu, M.-È., & Soucek, L. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00010 · Cited by 295 · see citing works
Pathological Unfoldomics of Uncontrolled Chaos: Intrinsically Disordered Proteins and Human Diseases
Uversky, V. N., Davé, V., Iakoucheva, L. M., Malaney, P., Metallo, S. J., Pathak, R. R., & Joerger, A. C. (2014) · Chemical Reviews · doi:10.1021/cr400713r · Cited by 288 · see citing works
Smith, M. C. P., & Gestwicki, J. E. (2012) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2012.10 · Cited by 285 · see citing works
A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology
Eubanks, L. M., Rogers, C. J., Beuscher, Koob, G. F., Olson, A. J., Dickerson, T. J., & Janda, K. D. (2006) · Molecular Pharmaceutics · doi:10.1021/mp060066m · Cited by 270 · see citing works
Self-citationTargeting Protein–Protein Interactions for Therapeutic Intervention: A Challenge for the Future
Zinzalla, G., & Thurston, D. E. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.12 · Cited by 257 · see citing works
Small Molecules Targeting c-Myc Oncogene: Promising Anti-Cancer Therapeutics
Chen, B.-J., Wu, Y., Tanaka, Y., & Zhang, W. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.10190 · Cited by 247 · see citing works
MYC in Oncogenesis and as a Target for Cancer Therapies
Albihn, A., Johnsen, J. I., & Arsenian‐Henriksson, M. (2010) · Advances in cancer research · doi:10.1016/s0065-230x(10)07006-5 · Cited by 240 · see citing works
Multiple Independent Binding Sites for Small-Molecule Inhibitors on the Oncoprotein c-Myc
Hammoudeh, D. I., Follis, A. V., Prochownik, E. V., & Metallo, S. J. (2009) · Journal of the American Chemical Society · doi:10.1021/ja900616b · Cited by 232 · see citing works
Therapeutic Strategies to Inhibit MYCPreprint
McKeown, M. R., & Bradner, J. E. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a014266 · Cited by 226 · see citing works
MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies
Ahmadi, S. E., Rahimi, S., Zarandi, B., Chegeni, R., & Safa, M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01111-4 · Cited by 211 · see citing works
Two decades of recent advances of Ugi reactions: synthetic and pharmaceutical applications
Fouad, M. A., Abdel‐Hamid, H., & Ayoup, M. S. (2020) · RSC Advances · doi:10.1039/d0ra07501a · Cited by 200 · see citing works
A complex task? Direct modulation of transcription factors with small molecules
Koehler, A. N. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.03.022 · Cited by 189 · see citing works
Follis, A. V., Hammoudeh, D. I., Wang, H., Prochownik, E. V., & Metallo, S. J. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.09.011 · Cited by 183 · see citing works
Small-molecule inhibitors of the Myc oncoprotein
Fletcher, S., & Prochownik, E. V. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.005 · Cited by 153 · see citing works
Prochownik, E. V., & Vogt, P. K. (2010) · Genes & Cancer · doi:10.1177/1947601910377494 · Cited by 150 · see citing works
Self-citationSelective Inhibition of c-Myc/Max Dimerization and DNA Binding by Small Molecules
Kiessling, A., Sperl, B., Hollis, A., Eick, D., & Berg, T. (2006) · Chemistry & Biology · doi:10.1016/j.chembiol.2006.05.011 · Cited by 148 · see citing works
Shaginian, A., Whitby, L. R., Hong, S., Hwang, I., Farooqi, B., Searcey, M., Chen, J., Vogt, P. K., & Boger, D. L. (2009) · Journal of the American Chemical Society · doi:10.1021/ja810025g · Cited by 144 · see citing works
Self-citationUversky, V. N. (2010) · Expert Review of Proteomics · doi:10.1586/epr.10.36 · Cited by 141 · see citing works
Eubanks, L. M., Hixon, M. S., Jin, W., Hong, S., Clancy, C. M., Tepp, W. H., Baldwin, M. R., Malizio, C. J., Goodnough, M. C., Barbieri, J. T., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611213104 · Cited by 123 · see citing works
Self-citationClausen, D. M., Guo, J., Parise, R. A., Beumer, J. H., Egorin, M. J., Lazo, J. S., Prochownik, E. V., & Eiseman, J. L. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.170555 · Cited by 117 · see citing works
Inhibition of transcription factors with small organic molecules
Berg, T. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.07.023 · Cited by 115 · see citing works
Beaulieu, M.-È., Castillo, F., & Soucek, L. (2020) · Cells · doi:10.3390/cells9041038 · Cited by 110 · see citing works
Targeting intrinsically disordered proteins involved in cancer
Santofimia‐Castaño, P., Rizzuti, B., Xia, Y., Abián, O., Peng, L., Velázquez‐Campoy, A., Neira, J. L., & Iovanna, J. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03347-3 · Cited by 110 · see citing works
Perturbation of the c-Myc–Max Protein–Protein Interaction via Synthetic α-Helix Mimetics
Jung, K., Wang, H., Teriete, P., Yap, J. L., Chen, L., Lanning, M. E., Hu, A., Lambert, L. J., Holien, T., Sundan, A., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501440q · Cited by 94 · see citing works
Selective antagonism of cJun for cancer therapy
Brennan, A., Leech, J. T., Kad, N. M., & Mason, J. M. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01686-9 · Cited by 91 · see citing works
Pharmacophore identification of c-Myc inhibitor 10074-G5
Yap, J. L., Wang, H., Hu, A., Chauhan, J., Jung, K.-Y., Gharavi, R. B., Prochownik, E. V., & Fletcher, S. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.10.013 · Cited by 83 · see citing works
Selective Inhibition of c‐Myc/Max Dimerization by a Pyrazolo[1,5‐a]pyrimidine
Kiessling, A., Wiesinger, R., Sperl, B., & Berg, T. (2007) · ChemMedChem · doi:10.1002/cmdc.200600294 · Cited by 83 · see citing works
Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2006
Dolle, R. E., Bourdonnec, B. L., Goodman, A. J., Morales, G. A., Salvino, J. M., & Zhang, W. (2007) · Journal of Combinatorial Chemistry · doi:10.1021/cc700111e · Cited by 82 · see citing works
A Leap into the Chemical Space of Protein-Protein Interaction Inhibitors
Villoutreix, B. O., Labbé, C. M., Lagorce, D., Laconde, G., & Spérandio, O. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212802651571 · Cited by 68 · see citing works
Small Molecule Modulators of Transcription
Arndt, H. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200600285 · Cited by 68 · see citing works
Embryonal neural tumours and cell death
Johnsen, J. I., Kogner, P., Albihn, A., & Arsenian‐Henriksson, M. (2009) · APOPTOSIS · doi:10.1007/s10495-009-0325-y · Cited by 67 · see citing works
Methods of probing the interactions between small molecules and disordered proteins
Heller, G. T., Aprile, F. A., & Vendruscolo, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2563-4 · Cited by 62 · see citing works
Stabilizers of the Max Homodimer Identified in Virtual Ligand Screening Inhibit Myc Function
Jiang, H., Bower, K. E., Beuscher, A. E., Zhou, B., Bobkov, A. A., Olson, A. J., & Vogt, P. K. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.054858 · Cited by 62 · see citing works
Self-citationSmall-molecule perturbation of competing interactions between c-Myc and Max
Follis, A. V., Hammoudeh, D. I., Daab, A. T., & Metallo, S. J. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.12.025 · Cited by 60 · see citing works
Small molecule inhibitors of Myc/Max dimerization and Myc-induced cell transformation
Jin, S. K., Stover, J. S., Whitby, L. R., Vogt, P. K., & Boger, D. L. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.09.044 · Cited by 59 · see citing works
Self-citationA Small Molecule Stabilizes the Disordered Native State of the Alzheimer’s Aβ Peptide
Löhr, T., Kohlhoff, K. J., Heller, G. T., Camilloni, C., & Vendruscolo, M. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00116 · Cited by 50 · see citing works
Guo, Y.-F., Duan, J., Wang, J., Li, L., Wang, D., Liu, X.-Z., Yang, J., Zhang, H., Lv, J., Yang, Y., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aax8694 · Cited by 52 · see citing works
Small-Molecule Modulators of c-Myc/Max and Max/Max Interactions
Berg, T. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_90 · Cited by 52 · see citing works
Chauhan, J., Wang, H., Yap, J. L., Sabato, P. E., Hu, A., Prochownik, E. V., & Fletcher, S. (2014) · ChemMedChem · doi:10.1002/cmdc.201402189 · Cited by 49 · see citing works
Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy
Li, Z., Garner, A. L., Gloeckner, C., Janda, K. D., & Carlow, C. K. S. (2011) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0001411 · Cited by 49 · see citing works
Self-citationA small molecule antagonist of ghrelin O-acyltransferase (GOAT)
Garner, A. L., & Janda, K. D. (2011) · Chemical Communications · doi:10.1039/c1cc11817j · Cited by 48 · see citing works
Self-citationIdentification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins
Marasco, D., & Scognamiglio, P. L. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16047394 · Cited by 42 · see citing works
Co-Operativity between MYC and BCL-2 Pro-Survival Proteins in Cancer
Fairlie, W. D., & Lee, E. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062841 · Cited by 43 · see citing works
MYC the oncogene from hell: Novel opportunities for cancer therapy
Papadimitropoulou, A., Makri, M., & Zoidis, G. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116194 · Cited by 38 · see citing works
Proteomic Approaches in Understanding Action Mechanisms of Metal-Based Anticancer Drugs
Wang, Y., & Chiu, J. (2008) · Metal-Based Drugs · doi:10.1155/2008/716329 · Cited by 37 · see citing works
Gene Transactivation and Transrepression in MYC-Driven Cancers
Scafuro, M., Capasso, L., Carafa, V., Altucci, L., & Nebbioso, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073458 · Cited by 34 · see citing works
Yap, J. L., Chauhan, J., Jung, K., Chen, L., Prochownik, E. V., & Fletcher, S. (2012) · MedChemComm · doi:10.1039/c2md00289b · Cited by 32 · see citing works
Follis, A. V., Galea, C. A., & Kriwacki, R. W. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0659-4_3 · Cited by 31 · see citing works
Evaluation of “Credit Card” Libraries for Inhibition of HIV-1 gp41 Fusogenic Core Formation
Xu, Y. Y., Lü, H., Kennedy, J. P., Yan, X., McAllister, L. A., Yamamoto, N., Moss, J. A., Boldt, G. E., Jiang, S., & Janda, K. D. (2006) · Journal of Combinatorial Chemistry · doi:10.1021/cc0600167 · Cited by 31 · see citing works
Self-citationMultiple spatially related pharmacophores define small molecule inhibitors of OLIG2 in glioblastoma
Tsigelny, I. F., Mukthavaram, R., Kouznetsova, V. L., Chao, Y. S., Babić, I., Nurmemmedov, E., Pastorino, S., Jiang, P., Calligaris, D., Agar, N. Y. R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5633 · Cited by 29 · see citing works
Bagnasco, L., Tortolina, L., Biasotti, B., Castagnino, N., Ponassi, R., Tomati, V., Nieddu, E., Stier, G., Malacarne, D., & Parodi, S. (2007) · The FASEB Journal · doi:10.1096/fj.06-7082com · Cited by 28 · see citing works
Breaking Tolerance in a Mouse Model of Multiple Myeloma by Chemoimmunotherapy
Sharabi, A., & Haran‐Ghera, N. (2010) · Advances in cancer research · doi:10.1016/s0065-230x(10)07001-6 · Cited by 27 · see citing works
Kleine Moleküle als Transkriptionsmodulatoren
Arndt, H. (2006) · Angewandte Chemie · doi:10.1002/ange.200600285 · Cited by 20 · see citing works
Mining a Kröhnke Pyridine Library for Anti-Arenavirus Activity
Miranda, P. O., Cubitt, B., Jacob, N. T., Janda, K. D., & de la Torre, J. C. (2018) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.7b00236 · Cited by 19 · see citing works
Self-citationTran, H. N. A., Bongarzone, S., Carloni, P., Legname, G., & Bolognesi, M. L. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.01.149 · Cited by 19 · see citing works
Selective targeting of MYC mRNA by stabilized antisense oligonucleotides
Gill, T., Wang, H., Bandaru, R., Lawlor, M. A., Lu, C., Nieman, L. T., Tao, J., Zhang, Y., Anderson, D. G., Ting, D. T., et al. (2021) · Oncogene · doi:10.1038/s41388-021-02053-4 · Cited by 18 · see citing works
Garner, A. L., Fullagar, J. L., Day, J. A., Cohen, S. M., & Janda, K. D. (2013) · Journal of the American Chemical Society · doi:10.1021/ja404180x · Cited by 18 · see citing works
Self-citation12 Arylstibonic acids that inhibit the DNA binding of five B-ZIP dimers
Rishi, V., Oh, W., Heyerdahl, S. L., Zhao, J., Scudiero, D. A., Shoemaker, R. H., & Vinson, C. (2010) · Journal of Structural Biology · doi:10.1016/j.jsb.2010.02.013 · Cited by 16 · see citing works
Vpu Matchmakers as a Therapeutic Strategy for HIV Infection
Montal, M. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000246 · Cited by 16 · see citing works
Prediction of antiprion activity of therapeutic agents with structure–activity models
Venko, K., Župerl, Š., & Novič, M. (2013) · Molecular Diversity · doi:10.1007/s11030-013-9477-3 · Cited by 13 · see citing works
Posttranslational regulation of Myc by promyelocytic leukemia zinc finger protein
Jin, S. K., & Vogt, P. K. (2009) · International Journal of Cancer · doi:10.1002/ijc.24449 · Cited by 13 · see citing works
Self-citationChen, J., Sun, M., Chen, C., Jiang, B., & Fang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1016683 · Cited by 9 · see citing works
Wang, L., Ciganda, M., & Williams, N. (2012) · Eukaryotic Cell · doi:10.1128/ec.00316-12 · Cited by 8 · see citing works
Gao, J. T., Yin, J., Li, S., Jia, P., Hong, R., Chen, J., Qu, X., Zhang, Z., Li, M., & Zhao, H. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.117023 · Cited by 6 · see citing works
Protein–Protein Interaction Inhibitors in Cancer
Hardcastle, I. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12392-3 · Cited by 4 · see citing works
Identifying Critical Signaling Molecules for the Treatment of Cancer
Arvanitis, C., Bendapudi, P. K., Bachireddy, P., & Felsher, D. W. (2007) · Springer eBooks · doi:10.1007/978-3-540-31209-3_2 · Cited by 3 · see citing works
The use of small molecule probes to study spatially separated stimulus-induced signaling pathways
Kravchenko, V. V., Gloeckner, C., Stowe, G. N., Kang, Y. J., Tobias, P. S., Mathison, J. C., Ulevitch, R. J., Kaufmann, G. F., & Janda, K. D. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.01.024 · Cited by 2 · see citing works
Self-citationOncogenes and the Initiation and Maintenance of Tumorigenesis
Felsher, D. W., Arvanitis, C., Bendapudi, P. K., & Bachireddy, P. (2016) · Springer eBooks · doi:10.1007/978-1-59745-458-2_8 · Cited by 2 · see citing works
A Promising but Challenging Strategy for Cancer Treatment: Disruption of Myc-Max Heterodimerization
Kim, H., Yoo, M., & Jung, K.-Y. (2016) · International Journal of Clinical Pharmacology & Pharmacotherapy · doi:10.15344/2456-3501/2016/114 · Cited by 1 · see citing works
A small molecule stabilises the disordered native state of the Alzheimer’s Aβ peptidePreprint
Löhr, T., Kohlhoff, K. J., Heller, G. T., Camilloni, C., & Vendruscolo, M. (2021) · bioRxiv · doi:10.1101/2021.11.10.468059 · Cited by 2 · see citing works
A Leap into the Chemical Space of Protein–Protein Interaction Inhibitors
Villoutreix, B. O., Labbé, C. M., Lagorce, D., Laconde, G., & Spérandio, O. (2013) · Methods and principles in medicinal chemistry · doi:10.1002/9783527648207.ch4 · Cited by 1 · see citing works
A Novel Assay for the Quantification of Active Transcription Factors
Goodhand, I. M. (2011) · UPT. Syiah Kuala University Library (Syiah Kuala University)
Franz, A. K., Shaw, J. T., & Tang, Y. (2010) · doi:10.1002/9780470972137.ch7
Sheng, L. (2017) · Texas ScholarWorks (Texas Digital Library) · doi:10.15781/t26t0hb97
Synthetic Approaches and Challenges to Transcription Factor Inhibitors
Procopiou, G., & Procopiou, P. A. (2018) · Royal Society of Chemistry eBooks · doi:10.1039/9781782624011-00001
Small-molecule Inhibitors of Myc–Max Interaction and DNA Binding
Fletcher, S., & Prochownik, E. V. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016544-00302
(2006) · BioTechniques · doi:10.2144/000112185
Combinatorial Chemistry Online
Terrett, N. K. (2006) · Combinatorial Chemistry - an Online Journal · doi:10.1016/j.comche.2006.04.001
Budamagunta, M. S., Mori, H., Silk, J., Slez, R. R., Bognár, B., Mendiola, U. R., Kálai, T., Maezawa, I., & Voss, J. C. (2024) · Antioxidants · doi:10.3390/antiox13111411
Sanz, A. M. (2014) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Chemical intervention strategies targeting MYC for cancer therapy
Wu, D., Zhu, Y., Ye, M., Guo, X., Jiang, Z., & Zhang, X. (2026) · Drug Discovery Today · doi:10.1016/j.drudis.2026.104726
BindingDB Entry 50042315: Pharmacophore identification of c-Myc inhibitor 10074-G5.
BindingDB (2013) · UC San Diego · doi:10.7270/q2wm1fpm
BindingDB (2020) · UC San Diego · doi:10.7270/q2w3809s
BindingDB Entry 50021153: MYC the oncogene from hell: Novel opportunities for cancer therapy.
BindingDB (2025) · UC San Diego · doi:10.7270/q2qz2gkz
- Authors
- Xu, Y., Shi, J., Yamamoto, N., Moss, J. A., Vogt, P. K., & Janda, K. D.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Vogt, Peter K.
- Janda, Kim D.
- Venue
- Bioorganic & Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 14
- Issue
- 8
- Pages
- 2660-2673
- ISSN
- 0968-0896 (ISSN-L)
- OpenAlex
- W2087562553
- Cited by
- 93
- References
- 68
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 3 · 2012: 8
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic & Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- protein-protein interaction disruption, c-Myc, Max, bHLH-Zip transcription factors, small organic molecules, focused compound libraries, cancer therapeutics, chicken embryo fibroblasts
- MeSH terms
- Animals, Cells, Cultured, Chickens, Circular Dichroism, Humans, Magnetic Resonance Spectroscopy, Protein Binding, DNA Probes, Proto-Oncogene Proteins c-myc, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Electrophoretic Mobility Shift Assay, Fluorescence Resonance Energy Transfer, Basic-Leucine Zipper Transcription Factors
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