Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC

NIH Image to ImageJ: 25 years of image analysis

Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638

Salmon provides fast and bias-aware quantification of transcript expression

Patro, R., Duggal, G., Love, M. I., Irizarry, R. A., & Kingsford, C. (2017) · Nature Methods · doi:10.1038/nmeth.4197 · Cited by 12,700

AP-1 function and regulation

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Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

Molina, D. M., Jafari, R., Ignatushchenko, M., Seki, T., Larsson, E. A., Dan, C., Sreekumar, L., Cao, Y., & Nordlund, P. (2013) · Science · doi:10.1126/science.1233606 · Cited by 2,261

Quantitative reactivity profiling predicts functional cysteines in proteomes

Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., & Cravatt, B. F. (2010) · Nature · doi:10.1038/nature09472 · Cited by 1,684

Reflecting on 25 years with MYC

Meyer, N., & Penn, L. Z. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2231 · Cited by 1,575

Proteome-wide covalent ligand discovery in native biological systems

Backus, K. M., Correia, B. E., Lum, K. M., Forli, S., Horning, B. D., González-Páez, G. E., Chatterjee, S., Lanning, B. R., Teijaro, J. R., Olson, A. J., et al. (2016) · Nature · doi:10.1038/nature18002 · Cited by 940

Drugging the ‘undruggable’ cancer targets

Dang, C. V., Reddy, E. P., Shokat, K. M., & Soucek, L. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.36 · Cited by 927

Targeting oncogenic Myc as a strategy for cancer treatment

Chen, H., Liu, H., & Qing, G. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0008-7 · Cited by 834

MYC: Connecting selective transcriptional control to global RNA production

Kress, T. R., Sabò, A., & Amati, B. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3984 · Cited by 521

Covalent Adducts Formed by the Androgen Receptor Transactivation Domain and Small Molecule Drugs Remain Disordered

Zhu, J., & Robustelli, P. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c00833 · Cited by 6

What’s been Hapten-ing over the last 88 years?

Thomson, P., Hammond, S., Meng, X., & Naisbitt, D. J. (2023) · Medicinal Chemistry Research · doi:10.1007/s00044-023-03091-1 · Cited by 7

Oligomerization enables the selective targeting of intrinsically disordered regions by small moleculesPreprint

Bielskutė, S., Mateos, B., Awawdy, M., Garcia‐Cabau, C., Niskanen, H., Sánchez, C., Bracaglia, L., Pierattelli, R., Felli, I. C., Frigolé‐Vivas, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.21.644603 · Cited by 6

Discovery of an NF-κB1 p105 Degrader for Anti-Inflammatory Therapy via Structural Optimization of the Coumarin Natural Product Minutuminolate

Choo, M. Z. Y., Lim, E., Wong, W. S. F., & Chai, C. L. L. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00055 · Cited by 5

Unlocking the Radiosensitizing Potential of MYC Inhibition in Neuroendocrine Malignancies

Guo, Q., Yang, W., Robinson, G., Chaludiya, K., Abdulkadir, A. N., Roy, F. G., Shivakumar, D., Ahmad, A. N., Abdulkadir, S. A., & Kirschner, A. N. (2025) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2025.04.034 · Cited by 5

Native stem cell transcriptional circuits define cardinal features of high-risk leukemia

Wang, Q., Boccalatte, F. E., Xu, J., Gambi, G., Nadorp, B., Akter, F., Mullin, C., Melnick, A. F., Choe, E., McCarter, A. C., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20231349 · Cited by 5

ReCHEMbinant stapling enhances intracellular delivery and bioactivity of engineered protein inhibitors

Kahler, J. P., Ellenbroek, B. D., van der Noord, V. E., van de Water, B., & Pomplun, S. J. (2025) · Chem · doi:10.1016/j.chempr.2025.102839 · Cited by 4

Epithelial AhR Suppresses Allergen-Induced Oxidative Stress and Senescence via c-Myc Regulation

Chen, Z., Gu, W., Wan, R., Zeng, Y., Xiang, X., Ouyang, R., & Gao, P. (2025) · Antioxidants · doi:10.3390/antiox15010022 · Cited by 6

Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering

Edaibis, R., Akel, R., & Shin, J. A. (2025) · Transcription · doi:10.1080/21541264.2025.2453315 · Cited by 4

Conformational modulation of intrinsically disordered transactivation domains for cancer therapy

Vosselman, T., Sahin, C., Lane, D. P., Arsenian‐Henriksson, M., Landreh, M., & Lama, D. (2025) · PNAS Nexus · doi:10.1093/pnasnexus/pgaf152 · Cited by 4

A covalent inhibitor targeting Cys16 on RhoA in colorectal cancer

Koo, T.-Y., Li, J. Y. K., Lee, N.-S., Chen, J., Yip, H. Y.-Y., Huang, I. B., Ng, K. Y., Yan, H. H. N., Leung, S. Y., Ma, S., et al. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.08.004 · Cited by 5

Lysosome‐Mediated Targeted Protein Degradation: Emerging Chimeric Platforms for Extracellular and Intracellular Therapeutics

Asadi, S., Taheri‐Torbati, M., Kesharwani, P., & Sahebkar, A. (2025) · Drug Development Research · doi:10.1002/ddr.70197 · Cited by 4

Structure‐based design of antibodies targeting the EBNA1 DNA‐binding domain to block Epstein–Barr virus latent infection and tumor growth

Han, Y., Wu, F., Zhang, Y., Liu, J., Wu, Y., Wang, Y., Jiang, X., Chen, X., & Xü, W. (2024) · MedComm · doi:10.1002/mco2.739 · Cited by 4

Systematic Targeting of Protein Complexes with Molecular COUPLrs

Yang, D., Harry, S. A., Chong, H. B., Khandelwal, N., Zhang, E., Nordenfelt, N. S., Chen, N. J., Lee, C., Kaluziak, S. T., Codd, E. M., et al. (2026) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-2314 · Cited by 4

Why are there no clinically-approved drugs targeting disordered proteins?

Löhr, T., Karunanithy, G., & Heller, G. T. (2026) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2026.103236 · Cited by 4

l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression

Gu, W., Wang, X., Solmonson, A., Cai, L., Xiao, Y., Tasdogan, A., Franklin, J., Zhang, Y., Zhang, H., Westfall, A. K., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci197010 · Cited by 3

Expedited SARS‐CoV‐2 Main Protease Inhibitor Discovery through Modular ‘Direct‐to‐Biology’ Screening

Wilders, H., Biggs, G. S., Rowe, S. M., Cawood, E. E., Riziotis, I. G., Rendina, A. R., Grant, E. K., Pettinger, J., Fallon, D. J., Skehel, M. J., et al. (2024) · Angewandte Chemie · doi:10.1002/ange.202418314 · Cited by 4

Designing the Proteome with Chemical Tools: Degrons and Beyond

Seabrook, L. J., Livelo, C. R., & Albrecht, L. V. (2025) · ChemBioChem · doi:10.1002/cbic.202500345 · Cited by 2

Disruption of c-Myc/Max heterodimerization induced by a novel anticancer agent endowed with 1,3-diphenylurea moiety: an in silico, chemoproteomics-based, and in vitro combined approach

Gazzillo, E., Capasso, L., Scala, F., Aliberti, M., Capuano, A., D’Urso, G., Bruno, I., Mele, D., Reginelli, A., Lauro, G., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.146187 · Cited by 2

Chromatin Regulatory Targets for Anticancer Therapeutics

Barta, P. A., Carter, T. R., & Erb, M. A. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00231 · Cited by 2

AlphaFold‐Guided Discovery of an Overlapping MYC/Miz‐1 Interface Enables Peptidomimetic Disruption of MYC/MAX

Ellenbroek, B. D., Tirtosentono, A. S. S., & Pomplun, S. J. (2025) · ChemMedChem · doi:10.1002/cmdc.202500740 · Cited by 2

Structure-Guided Optimization of 4-Chloro-Pyrazolopyridine Analogs for Covalent PREP Inhibition

Thakur, K., Fucci, I. J., Pandian, J., Suazo, K. F., Monteiro, D. C. F., & Yoo, E. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02680 · Cited by 2

Insights into the Design of MYC-Targeting Proteolysis Targeting Chimeras (PROTACs)

Alfayomy, A. M., Hagemann, S., Schmidt, M., Fouad, A. M., El‐Zahabi, M. A., Hüttelmaier, S., & Sippl, W. (2026) · Molecules · doi:10.3390/molecules31061011 · Cited by 2

Late-stage functionalization with strain-release warheads enables tunable covalent inhibition

Shultz, Z. P., Lee-Sam, A., Chang, Y., Sun, L., Grassie, D., Gabellini, A., Pedretty, K. P., Scattolin, T., Izumi, V., Fang, B., et al. (2026) · Science · doi:10.1126/science.adx7219 · Cited by 2

A Nucleophilic Chemical Probe Targeting Electrophilic Functional Groups in an Untargeted Way to Explore Cysteine Modulators in Natural Products

Gao, Y., Li, K., Zhang, L., Chen, C., & Bai, C. (2022) · ACS Chemical Biology · doi:10.1021/acschembio.2c00385 · Cited by 2

Designer Frankenproteins That Halt the Proliferation of Myc-Driven Cancer Cells

Ali, M. A., Akel, R., He, F., Piquette‐Miller, M., & Shin, J. A. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01493 · Cited by 2

Insights and Future Perspectives of Covalent Protein Degraders

Zhang, X. (2022) · Wiley eBooks · doi:10.1002/9783527836208.ch8 · Cited by 2

Extreme structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programsPreprint

Xie, T., Danieli‐Mackay, A., Buccarelli, M., Barbieri, M., Papadionysiou, I., D’Alessandris, Q. G., Übelmesser, N., Vinchure, O. S., Lauretti, L., Fotia, G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.20.537702 · Cited by 2

Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYCPreprint

Rosen, H. T., Li, K., Li, E. L., Currier, B., Brittain, S. M., García, F., Beard, D. C., Haenni‐Holzinger, S., Dovala, D., McKenna, J. M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.24.639755 · Cited by 2

Covalent Modulators of Immune Regulatory Transcription Factors IRF8 and IRF5Preprint

Cong, T. D., Chan, H., Greene, J., Sabaat, S., Ludwig, C., Abell, N. S., Albert, M. L., Kosuri, S., & Nomura, D. K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.03.668300 · Cited by 2

Proximity-enhanced cysteine–histidine crosslinking for elucidating intrinsically disordered and other protein complexes

Wu, Q., van den Wildenberg, S. A. H., Brzoskowski, J. C. R., van den Oetelaar, M. C. M., Verhoef, C. J. A., Genet, S. A. A. M., Ottmann, C., Markvoort, A. J., Brunsveld, L., & Cossar, P. J. (2025) · Chemical Science · doi:10.1039/d4sc07419j · Cited by 1

MYC: Master Regulator of Cell Death and Tumor Progression

Capasso, L., Mele, D., Fayyaz, F., Altucci, L., & Nebbioso, A. (2025) · Biochemistry · doi:10.5772/intechopen.1008763 · Cited by 2

Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

Pradeep, S. P., DiVasto, B. E., Glazer, P. M., & Bahal, R. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102804 · Cited by 1

Damage to newly synthesized proteins is a major cause of Cd(II) toxicity counteracted by proteasomes and integrated stress response in human cells

Ursu, G. M., & Zhitkovich, A. (2026) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2026.112045 · Cited by 1

No Time to Fold: Intrinsically Disordered Microproteins in Action

Chen, T., Cao, K., & Martinez, T. F. (2026) · Biochemistry · doi:10.1021/acs.biochem.6c00280 · Cited by 1

Intracellular Delivery of Antibody‐Based Therapeutics for Targeted Oncogenic c‐Myc Degradation in Mammalian Cells and Mice

Peng, L., Chen, J., Liu, X., Yan, J., Gan, Y., Fang, C., Ge, J., Yao, S. Q., & Yuan, P. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.6002660 · Cited by 1

Selective inhibitors of JAK1 targeting a subtype-restricted allosteric cysteinePreprint

Kavanagh, M. E., Horning, B. D., Khattri, R., Roy, N., Lu, J. P., Whitby, L. R., Brannon, J. C., Parker, A., Chick, J. M., Eissler, C. L., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.31.478302 · Cited by 1

"El soneto a Granada" de Pablo Antonio Cuadrado

Urbina, N. (2010) · Hispanic poetry review

DMCCB Basel Symposium 2022: Intrinsically Disordered Proteins as Drug Targets, Online, 31st January, 2022

Williams, E. T., & Hartrampf, N. (2022) · CHIMIA International Journal for Chemistry · doi:10.2533/chimia.2022.493

Covalent drug approach for targeting the undruggable proteome

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We are MedChem: The Frontiers in Medicinal Chemistry 2024

Schiedel, M., Barbie, P., Pape, F., Pinto, M., Lopez, A. U., Méndez, M. M., Heßler, G., Merk, D., Gehringer, M., & Lamers, C. (2024) · ChemMedChem · doi:10.1002/cmdc.202400543

Modulation of Iron Metabolism by New Chemicals Interacting with the Iron Regulatory SystemPreprint

Tsuji, Y., Ninomiya‐Tsuji, J., Shen, M. Y. F., & DiFrancesco, B. R. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4960121

Functional screen for mediators of onco-mRNA translation specificityPreprint

Kovalski, J. R., Sarioglu, G., Subramanyam, V., Hernandez, G. A., Rademaker, G., Osés-Prieto, J. A., Slota, M. J., Mohan, N., Yiakis, K., Liu, I., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.10.617637

FKBP9 enhances IGF2BP1-mediated m6A recognition to promote hepatocellular carcinoma progression

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The Effect of Myc Inhibition Combined with the Synergistic Effect of Photothermal, Photodynamic and Radiotherapy in Tumor Treatment

Cui, Y., Yang, W., Liu, W., Li, Y., Yu, C., Yu, C., Liu, Y., Xu, D., & Zhu, X. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s526592

Cyclometalated Gold(III)‐Mediated Cysteine Arylation: A Bioorthogonal Platform for Covalent Targeting of Intrinsically Disordered Proteins

Munugoda, U., Gilpatrick, S. T., Das, D., Parkin, S., Miller, A., & Awuah, S. G. (2025) · Angewandte Chemie · doi:10.1002/ange.202516331

Mild Transsulfinamidation Enables Rapid Access to Sulfinamides, Sulfonamides, and Sulfonimidamides

Baptiste, C. J., Shultz, Z. P., & Lopchuk, J. M. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c01806

Chemical Induction of MYC Protein Degradation via MYC–MAX Disruption and 20S Proteasome Activation

Olatunde, M. O., & Tepe, J. J. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.6c00258

Targeting conventionally intractable cancer-driving proteins: What has been achieved recently?

Xie, Q., Xu, W., Wang, Y., & Ma, X. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119102

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

Drugging the proteome via large-scale chemoproteomics

Li, Y., Wang, J., Wang, T., 柯细松, & 曲翊 (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.06.005

Progressive intestinal tumor cell plasticity, Myc activation, and loss of Lgr5 + tumor stem cell lineage commitment upon Wnt depletion

Lassila, M., Seyednasrollah, F., Bessone, C., Räisänen, M., Vuori, I., Berta, D. G., Aspholm, J., Petrova, T. V., Aaltonen, L. A., Alitalo, K. K., et al. (2026) · Science Advances · doi:10.1126/sciadv.aeb8564

Intracellular Delivery of Antibody‐Based Therapeutics for Targeted Oncogenic c‐Myc Degradation in Mammalian Cells and Mice

Peng, L., Chen, J., Liu, X., Yan, J., Gan, Y., Fang, C., Ge, J., Yao, S. Q., & Yuan, P. (2026) · Angewandte Chemie · doi:10.1002/ange.6002660

Downsizing Electrophilic MAX‐Derived Helical Zipper Peptides to Covalently Bind and Degrade Oncogenic MYC

de Araujo, A. D., Luo, L., Azad, M. G., Yu, M., Mason, J. M., Lim, J., Hill, T. A., & Fairlie, D. P. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.4950007

Downsizing Electrophilic MAX‐Derived Helical Zipper Peptides to Covalently Bind and Degrade Oncogenic MYC

de Araujo, A. D., Luo, L., Azad, M. G., Yu, M., Mason, J. M., Lim, J., Hill, T. A., & Fairlie, D. P. (2026) · Angewandte Chemie · doi:10.1002/ange.4950007

BindingDB Entry 50019872: Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.

BindingDB (2024) · UC San Diego · doi:10.7270/q2gb28f9

Discovery of a Covalent Ligand Targeting an Intrinsically Disordered Cysteine Within MYC \n

Boike, L., Cioffi, A. G., Majewski, F. C., Co, J., Henning, N. J., Jones, M. D., Liu, G., McKenna, J. M., Tallarico, J. A., Schirle, M., et al. (2020) · The Novartis Repository (Novartis)

Discovery of a Covalent Ligand Targeting an Intrinsically Disordered Cysteine Within MYC

Boike, L., Cioffi, A. G., Majewski, F. C., Co, J., Henning, N. J., Jones, M. W., Liu, G., McKenna, J. M., Tallarico, J. A., Schirle, M., et al. (2020)

Nailing Down a Notoriously Elusive Cancer Target: Direct Inhibition of MYC by a Covalent Small Molecule

Henley, M. J., Doyle, S. K., & Koehler, A. N. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2020.12.014 · Cited by 11

Chemoproteomics-enabled Discovery of Covalent Inhibitors and Novel Induced Proximity Platforms

Boike, L. (2022) · eScholarship (California Digital Library)

Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYCPreprint

Rosen, H. T., Li, K., Li, E. L., Currier, B., Brittain, S. M., García, F., Beard, D. C., Haenni‐Holzinger, S., Dovala, D., McKenna, J. M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.24.639755 · Cited by 2