Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity
Open accessPublished version of a preprint
Abstract
This Perspective explores molecular glues and bifunctional compounds-proximity-inducing compounds-and offers a framework to understand and exploit their similarity to hotspots, missense mutations, and posttranslational modifications (PTMs). This view is also shown to be relevant to intramolecular glues, where compounds induce contacts between distinct domains of the same protein. A historical perspective of these compounds is presented that shows the field has come full circle from molecular glues targeting native proteins, to bifunctionals targeting fusion proteins, and back to molecular glues and bifunctionals targeting native proteins. Modern screening methods and data analyses with pre-selected target proteins are shown to yield either cooperative molecular glues or bifunctional compounds that induce proximity, thereby enabling novel functional outcomes.
Integrity signals
Registry
Cites
Statistics
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?
The underlying principles of molecular glue mechanisms might be rooted in partial mimicry of naturally occurring PPIs at preexisting sites of high PPI propensity, interactions further enhanced by a matching molecular glue.
“Taken together, our findings provide another example that the underlying principles of molecular glue mechanisms might be rooted in the partial mimicry of naturally occurring PPIs at preexisting sites of high PPI propensity, interactions that are further enhanced by a matching molecular glue1,10,11,50–54.”
From Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry (2026) · cites this paper as [1]
Cites
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116 · see citing works
Self-citationPROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395 · see citing works
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M. (1993) · Cell · doi:10.1016/0092-8674(93)90384-3 · Cited by 2,387 · see citing works
Identification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136 · see citing works
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053 · see citing works
Self-citationA Hot Spot of Binding Energy in a Hormone-Receptor Interface
Clackson, T., & Wells, J. A. (1995) · Science · doi:10.1126/science.7529940 · Cited by 1,987 · see citing works
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879 · see citing works
Self-citationThe Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583 · see citing works
Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy
Di Stasi, A., Tey, S.-K., Dotti, G., Fujita, Y., Kennedy-Nasser, A., Martinez, C., Straathof, K., Liu, E., Durett, A. G., Grilley, B., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106152 · Cited by 1,512 · see citing works
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509 · see citing works
The dTAG system for immediate and target-specific protein degradation
Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118 · see citing works
mTOR kinase structure, mechanism and regulation
Yang, H., Rudge, D. G., Koos, J. D., Vaidialingam, B., Yang, H. J., & Pavletich, N. P. (2013) · Nature · doi:10.1038/nature12122 · Cited by 1,075 · see citing works
Encoded combinatorial chemistry.
Brenner, S., & Lerner, R. A. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5381 · Cited by 1,014 · see citing works
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
Choi, J., Chen, J., Schreiber, S. L., & Clardy, J. (1996) · Science · doi:10.1126/science.273.5272.239 · Cited by 933 · see citing works
Self-citationAllosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases
Chen, Y.-N. P., LaMarche, M. J., Chan, H. M., Fekkes, P., Garcia-Fortanet, J., Acker, M. G., Antonakos, B., Chen, C. H.-T., Chen, Z., Cooke, V. G., et al. (2016) · Nature · doi:10.1038/nature18621 · Cited by 925 · see citing works
Controlling Signal Transduction with Synthetic Ligands
Spencer, D. M., Wandless, T. J., Schreiber, S. L., & Crabtree, G. R. (1993) · Science · doi:10.1126/science.7694365 · Cited by 845 · see citing works
Self-citationSchreiber, S. L. (2021) · Cell · doi:10.1016/j.cell.2020.12.020 · Cited by 598 · see citing works
Self-citationStructure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53
Martinez-Zapien, D., Ruiz, F. X., Poirson, J., Mitschler, A., Ramirez, J., Forster, A., Cousido-Siah, A., Masson, M., Pol, S. V., PODJARNY, A. D., et al. (2016) · Nature · doi:10.1038/nature16481 · Cited by 487 · see citing works
Chemically induced proximity in biology and medicine
Stanton, B. Z., Chory, E. J., & Crabtree, G. R. (2018) · Science · doi:10.1126/science.aao5902 · Cited by 475 · see citing works
Burgin, A. B., Magnússon, Ó. Þ., Singh, J., Witte, P., Staker, B. L., Björnsson, J. M., Þorsteinsdóttir, M., Hrafnsdóttir, S., Hagen, T. J., Kiselyov, A. S., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1598 · Cited by 396 · see citing works
Signaling Network Model of Chromatin
Schreiber, S. L., & Bernstein, B. (2002) · Cell · doi:10.1016/s0092-8674(02)01196-0 · Cited by 395 · see citing works
Self-citationRheb Activates mTOR by Antagonizing Its Endogenous Inhibitor, FKBP38
Bai, X., Ma, D., Liu, A., Shen, X., Wang, Q. J., Liu, Y., & Jiang, Y. (2007) · Science · doi:10.1126/science.1147379 · Cited by 382 · see citing works
Peterson, R., Beal, P., Comb, M., & Schreiber, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.10.7416 · Cited by 355 · see citing works
Self-citationProbing Immunosuppressant Action with a Nonnatural Immunophilin Ligand
Bierer, B. E., Somers, P. K., Wandless, T. J., Burakoff, S. J., & Schreiber, S. L. (1990) · Science · doi:10.1126/science.1700475 · Cited by 351 · see citing works
Self-citationGarcia Fortanet, J., Chen, C. H.-T., Chen, Y.-N. P., Chen, Z., Deng, Z., Firestone, B., Fekkes, P., Fodor, M., Fortin, P. D., Fridrich, C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00680 · Cited by 298 · see citing works
Udaka, K., Tsomides, T. J., & Eisen, H. N. (1992) · Cell · doi:10.1016/0092-8674(92)90617-l · Cited by 280 · see citing works
Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation
Zhu, G., Xie, J., Kong, W., Xie, J., Li, Y., Du, L., Zheng, Q., Sun, L., Guan, M., Li, H., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.002 · Cited by 267 · see citing works
Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS
Schulze, C. J., Seamon, K. J., Zhao, Y., Yang, Y. C., Cregg, J., Kim, D., Tomlinson, A., Choy, T. J., Wang, Z., Sang, B., et al. (2023) · Science · doi:10.1126/science.adg9652 · Cited by 264 · see citing works
Haggarty, S. J., Mayer, T. U., Miyamoto, D. T., Fathi, R., King, R. W., Mitchison, T. J., & Schreiber, S. L. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00101-0 · Cited by 251 · see citing works
Self-citationTomasello, G., Armenia, I., & Molla, G. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa009 · Cited by 232 · see citing works
Chemical probes and drug leads from advances in synthetic planning and methodology
Gerry, C. J., & Schreiber, S. L. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.53 · Cited by 228 · see citing works
Self-citationTargeted protein degradation via intramolecular bivalent glues
Hsia, O., Hinterndorfer, M., Cowan, A. D., Iso, K., Ishida, T., Sundaramoorthy, R., Nakasone, M. A., Imrichova, H., Schätz, C., Rukavina, A., et al. (2024) · Nature · doi:10.1038/s41586-024-07089-6 · Cited by 222 · see citing works
Molecular glue CELMoD compounds are regulators of cereblon conformation
Watson, E. R., Novick, S., Matyskiela, M. E., Chamberlain, P. P., H. de la Peña, A., Zhu, J., Tran, E., Griffin, P. R., Wertz, I. E., & Lander, G. C. (2022) · Science · doi:10.1126/science.add7574 · Cited by 208 · see citing works
Unifying principles of bifunctional, proximity-inducing small molecules
Gerry, C. J., & Schreiber, S. L. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0469-1 · Cited by 199 · see citing works
Self-citationLiberles, S. D., Diver, S. T., Austin, D. J., & Schreiber, S. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.7825 · Cited by 199 · see citing works
Self-citationPhosphorylation-Inducing Chimeric Small Molecules
Siriwardena, S. U., Godage, D. N. P. M., Shoba, V. M., Lai, S., Shi, M., Wu, P., Chaudhary, S. K., Schreiber, S. L., & Choudhary, A. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c05537 · Cited by 196 · see citing works
Self-citationThe E3 ligase adapter cereblon targets the C-terminal cyclic imide degron
Ichikawa, S., Flaxman, H. A., Xu, W., Vallavoju, N., Lloyd, H. C., Wang, B., Shen, D., Pratt, M. R., & Woo, C. M. (2022) · Nature · doi:10.1038/s41586-022-05333-5 · Cited by 195 · see citing works
A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy
Wojtaszek, J. L., Chatterjee, N., Najeeb, J., Ramos, A., Lee, M., Bian, K., Xue, J. Y., Fenton, B. A., Park, H., Li, D., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.028 · Cited by 194 · see citing works
Kelly, J. D., Haldeman, B. A., Grant, F. J., et al. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31541-2 · Cited by 193 · see citing works
Dekker, C., Mattes, H., Wright, M., Boettcher, A., Hinniger, A., Hughes, N., Kapps-Fouthier, S., Eder, J., Erbel, P. J. A., Stiefl, N., et al. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167309 · Cited by 183 · see citing works
Molecular structures reveal synergistic rescue of Δ508 CFTR by Trikafta modulators
Fiedorczuk, K., & Chen, J. (2022) · Science · doi:10.1126/science.ade2216 · Cited by 176 · see citing works
Rewiring cancer drivers to activate apoptosis
Gourisankar, S. P., Krokhotin, A., Ji, W., Liu, X., Chang, C.-Y., Kim, S. H., Li, Z., Wenderski, W., Simanauskaite, J., Yang, H., et al. (2023) · Nature · doi:10.1038/s41586-023-06348-2 · Cited by 172 · see citing works
Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization
Spencer, D. M., Belshaw, P. J., Chen, L., Ho, S. N., Randazzo, F. M., Crabtree, G. R., & Schreiber, S. L. (1996) · Current Biology · doi:10.1016/s0960-9822(02)00607-3 · Cited by 144 · see citing works
Self-citationMechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2
Pádua, R. A. P., Sun, Y., Marko, I., Pitsawong, W., Stiller, J. B., Otten, R., & Kern, D. (2018) · Nature Communications · doi:10.1038/s41467-018-06814-w · Cited by 133 · see citing works
Stabilization of the Max Homodimer with a Small Molecule Attenuates Myc-Driven Transcription
Struntz, N. B., Chen, A., Deutzmann, A., Wilson, R. M., Stefan, E., Evans, H. L., Ramirez, M. A., Liang, T., Caballero, F., Wildschut, M. H. E., et al. (2019) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.02.009 · Cited by 130 · see citing works
Rapamycin-inspired macrocycles with new target specificity
Guo, Z., Hong, S. Y., Wang, J., Rehan, S., Liu, W., Peng, H., Das, M., Li, W., Bhat, S., Peiffer, B., et al. (2019) · Nature Chemistry · doi:10.1038/s41557-018-0187-4 · Cited by 120 · see citing works
A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling
Chen, J., & Fang, Y. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01263-7 · Cited by 116 · see citing works
DNA Barcoding a Complete Matrix of Stereoisomeric Small Molecules
Gerry, C. J., Wawer, M. J., Clemons, P. A., & Schreiber, S. L. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b01203 · Cited by 116 · see citing works
Self-citationThe expanding reaction toolkit for DNA-encoded libraries
Fair, R. J., Walsh, R. T., & Hupp, C. D. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2021.128339 · Cited by 110 · see citing works
SnapShot: Ca2+-Calcineurin-NFATSignaling
Crabtree, G. R., & Schreiber, S. L. (2009) · Cell · doi:10.1016/j.cell.2009.06.026 · Cited by 105 · see citing works
Self-citationAhn, G., Banik, S. M., & Bertozzi, C. R. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.02.024 · Cited by 96 · see citing works
Rational Design of Orthogonal Receptor–Ligand Combinations
Belshaw, P. J., Schoepfer, J. G., Liu, K., Morrison, K. L., & Schreiber, S. L. (1995) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199521291 · Cited by 93 · see citing works
Self-citationWestphal, M. V., Hudson, L., Mason, J. W., Pradeilles, J. A., Zécri, F. J., Briner, K., & Schreiber, S. L. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b13186 · Cited by 89 · see citing works
Self-citationStructure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
Garvie, C. W., Wu, X., Papanastasiou, M., Lee, S., Fuller, J., Schnitzler, G. R., Horner, S. W., Baker, A., Zhang, T., Mullahoo, J. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24495-w · Cited by 85 · see citing works
Proximity versus allostery: the role of regulated protein dimerization in biology
Austin, D. J., Schreiber, S. L., & Crabtree, G. R. (1994) · Chemistry & Biology · doi:10.1016/1074-5521(94)90002-7 · Cited by 84 · see citing works
Self-citationDNA-encoded library-enabled discovery of proximity-inducing small molecules
Mason, J. W., Chow, Y. T., Hudson, L., Tutter, A., Michaud, G., Westphal, M. V., Shu, W., Ma, X., Tan, Z. Y., Coley, C. W., et al. (2024) · Nature Chemical Biology · doi:10.1038/s41589-023-01458-4 · Cited by 83 · see citing works
Self-citationShigdel, U. K., Lee, S.-J., Sowa, M. E., Bowman, B. R., Robison, K., Zhou, M., Pua, K. H., Stiles, D. T., Blodgett, J. A. V., Udwary, D. W., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006560117 · Cited by 80 · see citing works
The protein organization of a red blood cell
Sae-Lee, W., McCafferty, C. L., Verbeke, E. J., Havugimana, P. C., Papoulas, O., McWhite, C. D., Houser, J. R., Vanuytsel, K., Murphy, G. J., Drew, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111103 · Cited by 78 · see citing works
Light‐Induced Dimerization Approaches to Control Cellular Processes
Klewer, L., & Wu, Y. (2019) · Chemistry - A European Journal · doi:10.1002/chem.201900562 · Cited by 77 · see citing works
Schreiber, S. L. (2018) · Israel Journal of Chemistry · doi:10.1002/ijch.201800113 · Cited by 76 · see citing works
Self-citationSystematic discovery of mutation-directed neo-protein-protein interactions in cancer
Mo, X., Niu, Q., Ivanov, A. A., Tsang, Y. H., Tang, C., Shu, C., Li, Q., Qian, K., Wahafu, A., Doyle, S. P., et al. (2022) · Cell · doi:10.1016/j.cell.2022.04.014 · Cited by 72 · see citing works
Quancard, J., Klein, T., Fung, S.-Y., Renatus, M., Hughes, N., Israël, L., Priatel, J. J., Kang, S., Blank, M. A., Viner, R. I., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-018-0222-1 · Cited by 72 · see citing works
Induced protein degradation for therapeutics: past, present, and future
Yoon, H., Rutter, J. C., Li, Y.-D., & Ebert, B. L. (2024) · Journal of Clinical Investigation · doi:10.1172/jci175265 · Cited by 70 · see citing works
Small-Molecule Kinase Downregulators
Jones, L. H. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.10.011 · Cited by 69 · see citing works
Rational Screening for Cooperativity in Small-Molecule Inducers of Protein–Protein Associations
Liu, S., Tong, B., Mason, J. W., Ostrem, J. M. L., Tutter, A. V., Hua, B. K., Tang, S. A., Bonazzi, S., Briner, K., Berst, F., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c08307 · Cited by 69 · see citing works
Self-citationCytokines and cell growth control.
Goldring, M. B., & Goldring, S. R. (1991) · PubMed · Cited by 65 · see citing works
Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach
Chen, Q., Liu, C., Wang, W., Meng, X., Cheng, X., Li, X.-Y., Cai, L., Luo, L., He, X., Qu, H., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.2c00797 · Cited by 55 · see citing works
Gibson, W. J., Sadagopan, A., Shoba, V. M., Choudhary, A., Meyerson, M. M., & Schreiber, S. L. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c06179 · Cited by 54 · see citing works
Self-citationConverging mechanism of UM171 and KBTBD4 neomorphic cancer mutations
Xie, X., Zhang, O., Yeo, M. J. R., Lee, C., Tao, R., Harry, S. A., Payne, N. C., Nam, E., Paul, L., Li, Y., et al. (2025) · Nature · doi:10.1038/s41586-024-08533-3 · Cited by 50 · see citing works
Solid-phase synthesis of DNA-encoded libraries via an “aldehyde explosion” strategy
Paciaroni, N. G., Ndungu, J. M., & Kodadek, T. J. (2020) · Chemical Communications · doi:10.1039/d0cc01474e · Cited by 45 · see citing works
Heitel, P. (2023) · Molecules · doi:10.3390/molecules28020690 · Cited by 27 · see citing works
Chemical inducers of dimerization: The atomic structure of FKBP12-FK1012A-FKBP12
Schultz, L. W., & Clardy, J. (1998) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(97)10195-0 · Cited by 21 · see citing works
Diversity-oriented synthesis encoded by deoxyoligonucleotides
Hudson, L., Mason, J. W., Westphal, M. V., Richter, M. J. R., Thielman, J. R., Hua, B. K., Gerry, C. J., Xia, G., Osswald, H. L., Knapp, J. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40575-5 · Cited by 15 · see citing works
Self-citationBinge, D. (1992) · Current Biology · doi:10.1016/0960-9822(92)90028-9 · Cited by 5 · see citing works
Flagged first, then by citations
2 of the 76 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- First International Congress on FK 506. August 21-24, 1991, Pittsburgh, PA (1991). Transplant. Proc. 23, 2709–3380.
- Xie, 2024, KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes, bioRxiv
Cited by
Sorted by citations
Targeted protein degradation for cancer therapy
Hinterndorfer, M., Spiteri, V. A., Ciulli, A., & Winter, G. E. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00817-8 · Cited by 245 · see citing works
“By binding the first protein, they modify its surface or conformation to enhance its binding affinity to the other protein 45,59 .”
Mining the CRBN target space redefines rules for molecular glue-induced neosubstrate recognition
Petzold, G., Gainza, P., Annunziato, S., Lamberto, I., Trenh, P., McAllister, L. A., DeMarco, B., Schwander, L., Bunker, R. D., Zlotosch, M., et al. (2025) · Science · doi:10.1126/science.adt6736 · Cited by 117 · see citing works
Cracking the EGFR code: Cancer biology, resistance mechanisms, and future therapeutic frontiers
Du, Y.-F., Karatekin, F., Wang, W. K., Hong, W., & Gandhi, T. K. B. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100076 · Cited by 86 · see citing works
Routes to molecular glue degrader discovery
Liu, Y., Bai, J., Li, D., & Cang, Y. (2025) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.12.006 · Cited by 45 · see citing works
Lessons learned in linking PROTACs from discovery to the clinic
Pike, A., Lee, E. C. Y., Michaelides, I. N., Schade, M., Sharma, A., Scott, J. S., & Srivastava, A. (2025) · Nature Reviews Chemistry · doi:10.1038/s41570-025-00784-6 · Cited by 48 · see citing works
“CRBN was found to be the molecular target of thalidomide, and subsequently, the molecular glue degrader mechanism-of-action 113,114 of thalidomide and other immunomodulatory imide drugs (IMiDs) (such as thalidomide, lenalidomide and pomalidomide) was elucidated 115,116 .”
Discovery of fully synthetic FKBP12-mTOR molecular glues
Deutscher, R. C. E., Meyners, C., Repity, M. L., Sugiarto, W. O., Kolos, J., Maciel, E. V. S., Heymann, T., Geiger, T. M., Knapp, S., Lermyte, F., et al. (2025) · Chemical Science · doi:10.1039/d4sc06917j · Cited by 35 · see citing works
Nussinov, R. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169044 · Cited by 33 · see citing works
Machine learning to predict de novo protein–protein interactions
Gaínza, P., Bunker, R. D., Townson, S. A., & Castle, J. C. (2025) · Trends in biotechnology · doi:10.1016/j.tibtech.2025.04.013 · Cited by 25 · see citing works
Direct-to-Biology Enabled Molecular Glue Discovery
Hu, M., Ochoada, J., Actis, M., McGowan, K. M., Jarusiewicz, J., Yoshimura, S., McGrath, L., Neelakantan, U., Aggarwal, A., Mayasundari, A., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c13496 · Cited by 23 · see citing works
Induced proximity at the cell surface
Till, N. A., Ramanathan, M., & Bertozzi, C. R. (2025) · Nature Biotechnology · doi:10.1038/s41587-025-02592-1 · Cited by 21 · see citing works
“The latter technologies take inspiration from the natural function of RNF43 (ring finger protein 43) and ZNRF3 (zinc and ring finger 3) in degrading Wnt receptors, which in turn regulates Wnt–β-catenin signaling 22 .”
How multispecific molecules are transforming pharmacotherapy
Deshaies, R. J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01262-w · Cited by 23 · see citing works
“This has led to growing interest in ‘molecular glues’ that are more compact, drug-like molecules that tend to bind with good affinity to only one partner, thereby creating a novel surface that recruits a second factor 74,75 .”
Discovery of DCAF16 binders for targeted protein degradation
Campos, M. A., Riha, I. A., Zhang, C.-L., Mozes, C., Scheidt, K. A., & Zhang, X.-Y. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.4c00799 · Cited by 18 · see citing works
Decoding the functional impact of the cancer genome through protein–protein interactions
Fu, H., Mo, X., & Ivanov, A. A. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00784-6 · Cited by 21 · see citing works
“Small-molecule glues , or bifunctional compounds, offer one way to bring interacting proteins into close proximity to restore or stabilize critical PPIs of tumour suppressors 230,231 .”
Exploring nondegrading molecular glues for protein–protein interactions
Yu, S., Zhou, L., Yang, J., Zhang, J., & Lu, W. (2025) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2025.07.005 · Cited by 18 · see citing works
The “three body solution”: Structural insights into molecular glues
Tomlinson, A. C. A., Knox, J. E., Brunsveld, L., Ottmann, C., & Yano, J. K. (2025) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2025.103007 · Cited by 17 · see citing works
Xiao, Z., Gavriil, E.-S., Cao, F., Zhang, X., Li, S. X., Kotelnikov, S., Michalska, P., Marte, F., Huang, C., Lu, Y., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c01420 · Cited by 17 · see citing works
“4 MGDs typically facilitate a cooperative protein − protein interaction (PPI), 5 and rational design of MGD is still challenging due to the complexity of the ternary complex interface.”
Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders
Zhuang, Z., Byun, W. S., Kozicka, Z., Donovan, K. A., Dwyer, B. G., Thornhill, A. M., Jones, H. M., Jiang, Z., Zhu, X., Fischer, E. S., et al. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202508427 · Cited by 17 · see citing works
Scaffold-hopping for molecular glues targeting the 14-3-3/ERα complex
Konstantinidou, M., Zingiridis, M., Pennings, M. A. M., Fragkiadakis, M., Virta, J. M., Revalde, J. L., Visser, E. J., Ottmann, C., Brunsveld, L., Neochoritis, C. G., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61176-4 · Cited by 17 · see citing works
“…the mechanism of action of molecular glues – small molecules that bind cooperatively at PPI interfaces and strengthen weak, pre-existing interactions – has enabled the stabilization of PPIs by taking into account the elements of cooperativity, molecular recognition and shape complementarity 6,7 .”
EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy
Gu, Y., He, H., Qiao, S., Shao, Y., Wang, L., Zhang, Z., Zhang, L., & Zhou, F. (2025) · Advanced Science · doi:10.1002/advs.202505785 · Cited by 17 · see citing works
Functional investigations of p53 acetylation enabled by heterobifunctional molecules
Chen, L.-Y., Singha Roy, S. J., Jadhav, A. M., Wang, W. W., Chen, P.-H., Bishop, T., Erb, M. A., & Parker, C. G. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00438 · Cited by 18 · see citing works
A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death
Nix, M. N., Gourisankar, S. P., Bowman, K., Nettles, S. A., Yang, H. H., Dwyer, B. G., Sarott, R. C., Abuzaid, H. Z., Martinez, M. M., Phillips, N. A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.06.037 · Cited by 16 · see citing works
Load and lock: An emerging class of therapeutics that influence macromolecular dissociation
Deshaies, R. J., & Potts, P. R. (2025) · Science · doi:10.1126/science.adx3595 · Cited by 17 · see citing works
Xu, Y., Zhao, W., Nie, H., Wang, J., Fu, J., Hu, H., Liu, Z., Tao, S., Zhang, M., Zhou, Y., et al. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202505053 · Cited by 15 · see citing works
Sandhof, C. A., Murray, H. F. B., Silva, M. C., & Haggarty, S. J. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00499 · Cited by 13 · see citing works
“These compounds could also be considered molecular glues [170] given that through binding to one protein, they promote change or stabilization of its tertiary structure, thereby increasing af fi nity for binding partners [172].”
Targeted Protein Acetylation Through Chemically Induced Proximity
Wang, W., Roy, S. J. S., & Parker, C. G. (2025) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5c00326 · Cited by 14 · see citing works
Chemical proteomic mapping of reversible small molecule binding sites in native systems
Wozniak, J. M., Li, W., & Parker, C. G. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.09.001 · Cited by 12 · see citing works
Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules
Forrest, I., Conway, L. P., Gathmann, C., Jadhav, A. M., Chiu, T.-Y., Chaheine, C. M., Estrada, M. A., Shrestha, A., Sarris, K., Reitsma, J. M., et al. (2025) · ACS Central Science · doi:10.1021/acscentsci.5c01594 · Cited by 12 · see citing works
Izaguirre, J. A., McDargh, Z. A., Trovato, F., Wu, Y., Palpant, T., Razavi, A. M., Koh, C. M., & Xu, H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.13.632817 · Cited by 11 · see citing works
Chen, Z., Chi, G., Balo, T., Chen, X., Montes, B. R., Clifford, S. C., D’Angiolella, V., Szabo, T., Kiss, A., Novak, T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58350-z · Cited by 10 · see citing works
Discovery of molecular glues that bind FKBP12 and novel targets using DNA-barcoded libraries
Zandi, T. A., Romanowski, M. J., Viscomi, J. S., Tan, Z. Y., Tong, B., Bonazzi, S., Zécri, F. J., Schreiber, S. L., & Michaud, G. A. (2024) · doi:10.1101/2024.12.09.627499 · Cited by 10 · see citing works
Self-citationA double-edged sword of neo-substrate degradation in PROTACs
Song, Z., Duan, C., Wu, M., Wang, Z., Pan, Y., Zhang, C., Huang, W., & Zeng, S. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118253 · Cited by 9 · see citing works
MGTbind: a comprehensive database of molecular glue ternary interactome
Zhu, J., Liao, Y., Lin, H., Xie, J., Deng, Z., Han, J., Zhang, Z., Xiao, J., Wang, Z., Zhang, S., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf1075 · Cited by 9 · see citing works
“The formation of ternary complex selectively rewires cellular interactomes, ultimately modulating protein functions, such as modification, stability, and degradation [ 10 –12 ].”
He, Y., Liao, T., Wang, X., Xiao, Q. H., Wang, H., He, R. R., Zhao, C., Tian, X., Gao, Q., & Hao, L. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108846 · Cited by 8 · see citing works
Cereblon induces G3BP2 neosubstrate degradation using molecular surface mimicry
Annunziato, S., Quan, C., Donckele, E. J., Lamberto, I., Bunker, R. D., Zlotosch, M., Schwander, L., Murthy, A., Wiedmer, L., Staehly, C., et al. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01738-8 · Cited by 9 · see citing works
“Targeted protein degradation by molecular glue degraders (MGDs) is an emergent therapeutic modality in which small-molecule compounds repurpose the activity of E3 ubiquitin ligases to recruit, ubiquitinate and induce degradation of nonnatural substrates called neosub-strates 1 .”
A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation
Langousis, G., Gaínza, P., Hunkeler, M., Kapsitidou, D., Donckèle, E. J., Annunziato, S., Wiedmer, L., Jones, K. F. M., DeMarco, B., Quan, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65094-3 · Cited by 8 · see citing works
“TPD mainly leverages compounds such as molecular glue degraders (MGDs) or proteolysis-targeting chimeras (PROTACs); many such compounds bind to the CRL4-CRBN ubiquitin ligase and promote recruitment of neosubstrates for ubiquitination and degradation 7 .”
Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5
Goetzke, F. W., Bernard, S. M., Ju, C., Pollock, J., DeMeester, K. E., Gross, J., Simon, G. M., He, C., Melillo, B. N., & Cravatt, B. F. (2026) · Nature Chemical Biology · doi:10.1038/s41589-025-02099-5 · Cited by 7 · see citing works
“Small molecules that induce protein–protein interactions through the formation of ternary complexes have become a major source of chemical probes and drugs 73 .”
Machine learning, docking, or physics for structure prediction of ligand-induced ternary complexes
Solazzo, R., Chen, S., & Riniker, S. (2026) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2025.103217 · Cited by 7 · see citing works
Expanding the reach of molecular glue degraders
Hartmann, M. D. (2025) · Science · doi:10.1126/science.ady4446 · Cited by 7 · see citing works
Exploiting the DCAF16–SPIN4 interaction to identify DCAF16 ligands for PROTAC development
Riha, I. A., Campos, M. A. L., Jin, X., Wang, F. Y., Zhang, C., Dunne, S. F., Cravatt, B. F., & Zhang, X. (2024) · RSC Medicinal Chemistry · doi:10.1039/d4md00681j · Cited by 6 · see citing works
Mo, X., Du, Y., & Fu, H. (2025) · ASPET Discovery · doi:10.1016/j.aspetd.2025.100003 · Cited by 6 · see citing works
NSD proteins in anti-tumor immunity and their therapeutic targeting by protein degraders
Chava, S., & Wajapeyee, N. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05806-6 · Cited by 6 · see citing works
Warhead Strategy for Targeted Protein S-Nitrosation
Zhang, C., Ye, H., Ji, D., Xiong, T., Yu, J., Qian, Z., Li, C., Li, H., Liang, Z., Zhang, Y., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c07409 · Cited by 6 · see citing works
Kashyap, D., Cadeddu, M., Oliver, P. L., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c09544 · Cited by 6 · see citing works
Molecular glues: A new path to the world of the unattainable
Khaledian, M., Sheikh, H., Babaei, F., Divsalar, A., Gharshasbi, M., Ottmann, C., Haertlé, T., Saboury, A. A., & Rasouli, M. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.148861 · Cited by 6 · see citing works
Dual E3 ligase recruitment by monovalent degraders for tunable SMARCA 2/4 degradation
Spiteri, V. A., Segal, D., Correa-Sáez, A., Iso, K., Casement, R., Ordoño, M. M. I., Nakasone, M. A., Sathe, G. J., Schätz, C., Peters, H. E., et al. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02224-y · Cited by 6 · see citing works
“Targeted protein degradation (TPD) is a therapeutic modality that can induce potent and selective depletion of protein levels through a catalytic mode of action 1–4 .”
Liu, Y., Hua, H. M., Cao, Y., Li, M., Zhang, H., Du, S., Liu, J., Luo, T. L., & Jiang, Y. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.05.004 · Cited by 6 · see citing works
Site-resolved assessment of targeted protein degradation
Moreno-Ballesteros, R., Pembridge, T., Beniwal, G., & Virdee, S. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.06.002 · Cited by 5 · see citing works
The rise of AlphaFold in drug design
Stecuła, A., Paul, R., Litchfield, K., Dalton, S. E., Low, C. M. R., Reis, C. R., & Congreve, M. (2025) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2025.09.002 · Cited by 4 · see citing works
Hydrogen/Deuterium Exchange for Chiral Stability Assessment in Acidic Methine-Containing Compounds
Yu, Z. J., Morfin, C., Paul, T., et al. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c04777 · Cited by 4 · see citing works
Gray, J. L., Xiao, Z., Rogga, V. V., Zhang, X., & Tate, E. W. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.5c12299 · Cited by 4 · see citing works
Zandi, T. A., Romanowski, M. J., Viscomi, J. S., Gunderson, K., Tan, Z. Y., Tong, B., Bonazzi, S., Zécri, F. J., Schreiber, S. L., & Michaud, G. A. (2026) · Nature Communications · doi:10.1038/s41467-026-71512-x · Cited by 4 · see citing works
Self-citationA general assay platform to study protein pharmacology using ligand-dependent structural dynamics
Ciulla, D. A., Dranchak, P. K., Aitha, M., van Neer, R. H. P., Shah, D., Tharakan, R., Wilson, K. M., Wang, Y., Braisted, J. C., & Inglese, J. (2025) · Nature Communications · doi:10.1038/s41467-025-59658-6 · Cited by 5 · see citing works
“…of possible confusion are that (1) the first target is itself a luciferase (so mention this explicitly) and (2) the use of a split luciferase system (which normally works by template mediated complementation in e.g. PPI), whereas the effect described here does not rely on a split enzyme system 2.”
Targeting oncogenic K-RAS mutants with small-molecule degrader XMU-MP-9 through NEDD4-1
Zeng, T., Jiang, T., Zhang, B., Zhang, T., Dai, W., Yin, X., Li, Y., Yu, Z., Wu, C., Wu, Y., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.07.031 · Cited by 3 · see citing works
“The proximity-inducing agents that can induce a close proximity between an E3 ubiquitin ligase and its non-native target protein include molecular glues and bifunctional compounds 28 .”
An, Y., Zhou, R., & Li, X. (2026) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5c00738 · Cited by 3 · see citing works
Mechanisms of inflammatory bowel diseases: Insights from human genetics and chemical biology
Graham, D. B., & Xavier, R. J. (2026) · Immunity · doi:10.1016/j.immuni.2026.04.002 · Cited by 3 · see citing works
Rudolph, J., Hoeflich, K. P., & Dar, A. C. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01411-9 · Cited by 8 · see citing works
“These compounds act by forcing a target kinase into proximity with an effector protein that imparts a pharmacological consequence 91,92 (Fig.”
Xu, Y., Zhao, W., Nie, H., Wang, J., Fu, J., Hu, H., Liu, Z., Tao, S., Zhang, M., Zhou, Y., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202505053 · Cited by 3 · see citing works
Reengineering of a Proteomimetic Pan‐Ras Inhibitor into a Ras Degrader
Ongkingco, J. F., Hong, S. H., Toth, E. D., Nguyễn, T. T., & Arora, P. S. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202507092 · Cited by 4 · see citing works
Yamada, K., Yamanaka, S., Yamakoshi, H., Kohyama, A., Iwabuchi, Y., Kosako, H., & Sawasaki, T. (2025) · Communications Biology · doi:10.1038/s42003-025-08761-x · Cited by 3 · see citing works
“For example, proteolysis-targeting chimeras (PRO-TACs) can target many proteins previously considered ‘ Undruggable Tar-gets ’ for conventional small molecule-mediated pharmacology 2,3 .”
Novel immune therapy: antibody-recruiting strategy
Manabe, Y., & Fukase, K. (2025) · Chemistry Letters · doi:10.1093/chemle/upaf035 · Cited by 2 · see citing works
Pennings, M. A. M., van den Bosch, M. A. W., Oberheide, A., Verhoef, C. J. A., Ottmann, C., Markvoort, A. J., Miley, G. P., & Brunsveld, L. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202521678 · Cited by 2 · see citing works
Emerging biologic modalities for targeted protein degradation
Caldwell, A. G., Parmar, H., & Zhang, X. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111248 · Cited by 2 · see citing works
Context-dependent synthetic lethality — an emerging precision therapeutic approach
Chang, L., Shaw, K. L., Vázquez, F., & Sellers, W. R. (2026) · Nature reviews. Cancer · doi:10.1038/s41568-026-00929-9 · Cited by 4 · see citing works
“The rational design and collection of diverse chemical libraries, such as imid-based scaffolds for molecular glues and electrophile warheads for cysteine modification 299,300 , could facilitate the screening and downstream medicinal chemistry efforts for drug discovery.”
Neigenfind, P., Gathmann, C., Cherney, E. C., et al. (2026) · Angewandte Chemie · doi:10.1002/ange.3989307 · Cited by 2 · see citing works
Neigenfind, P., Gathmann, C., Cherney, E. C., et al. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.3989307 · Cited by 2 · see citing works
Modulating phosphorylation by proximity-inducing strategy: an update
Xia, Y., Zhai, D., You, Q., Wang, L., & Zhang, Q. (2026) · RSC Medicinal Chemistry · doi:10.1039/d6md00484a · Cited by 2 · see citing works
Drug discovery technologies–Current and future trends
Noe, M. C., Steppan, C. M., & Weston, A. D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00019-4 · Cited by 1 · see citing works
Coomar, S., Gasser, J. A., Słabicki, M., Donovan, K., Fischer, E., Ebert, B. L., Gillingham, D., & Thomä, N. (2025) · RSC Medicinal Chemistry · doi:10.1039/d5md00054h · Cited by 1 · see citing works
Bakthavachalam, L., Sakthivel, K., Muruganantham, S., et al. (2025) · Discover Molecules · doi:10.1007/s44345-025-00025-9 · Cited by 1 · see citing works
Kaiser, T. M. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1691119 · Cited by 1 · see citing works
“…glues: agents that indeed are multiple ligands but interact with their targets to generate synthetic biological complexes with the ability to induce degradation (vepdegestrant, a PROTAC) or stabilize macromolecular complexes (tacrolimus, a molecular glue) (Békés et al., 2022; Schreiber, 2024).”
Neo‐Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein
Kumari, P., Oum, Y. H., Miller, E. J., Qui, M., Du, Y., Mou, H., Singh, R. K., Fu, H., & Mo, X. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.202512791 · Cited by 2 · see citing works
Yang, Y., Li, Y., Zhou, Z., Li, H. L., Ma, Y., Bi, W., Li, M., Liu, X., Jia, Q., Han, L., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121374 · Cited by 1 · see citing works
Exploration of protein degradability enables fully endogenous MrTAC degraders
Seabrook, L. J., Karaj, E., Sindi, S. H., Brodie, G., Livelo, C. R., Franco, C. N., Campos, M., Leonard, J. T., Gao, F., Skowronska‐Krawczyk, D., et al. (2026) · Chem · doi:10.1016/j.chempr.2026.102998 · Cited by 1 · see citing works
Biophysical Modeling Elucidates Mechanistic Principles for Rational Molecular Glue Design
Chae, S. J., DeBonis, J., Quinlan, J., Richards, R., Wang, J., Gutierrez, G. J., Tart, J., Couturier, M., Cuesta, S. M., Jin, M., et al. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c03125 · Cited by 1 · see citing works
“2,3 To understand how kinetic and thermodynamic parameters affect these diverse MG dynamics, we need a universal framework that comprehensively covers all MG mechanisms.”
Al-Karmalawy, A. A., Attia, M. I., Yousef, T. A., Al-Qazzan, M. B., Al-Akeedi, M., Khatib, A. O. A., & Hawas, S. S. (2026) · Archiv der Pharmazie · doi:10.1002/ardp.70261 · Cited by 1 · see citing works
“The ability of covalent glues to combine chemical perma-nence with biological selectivity offers notable pharmacological advantages [66].”
The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue
Hinshaw, S. M., Yuan, L., Noman, M. A. A., Martinez, M. J., Colombo, G. M., Dwyer, B. G., Ji, W., Romero, B. A., Forrest, I., Lu, J., et al. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.04.016 · Cited by 1 · see citing works
Al-Karmalawy, A. A., Sippl, W., Al-Dakhil, A., Yousef, T. A., Khatib, A. O. A., & Hawas, S. S. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110065 · Cited by 1 · see citing works
Tryptoline stereoprobe elaboration identifies inhibitors of the GRPEL1–HSPA9 complex
Hayward, R. E., Berkeley, R. F., Gao, Z., Garhammer, M., Morizono, M. A., Njomen, E., Li, H., DeMeester, K. E., Cociorva, V., Herzik, M. A., et al. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02348-1 · Cited by 1 · see citing works
Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders
Devarajappa, R., Kiyeleko, S., Hocine, S., Cosson, V., Calandrino, R., Baló, T., Bordelo, J. A., Triboulet, S., Caruana, L., Klipfel, L., et al. (2025) · Reactions · doi:10.3390/reactions6010020 · Cited by 1 · see citing works
“Acting as chemical inducers of proximity (CIPs) [8], such organic compounds have been called molecular glues [9–13].”
Targeting oncogenic K-Ras mutants with a small-molecule degrader through Nedd4-1Preprint
Zeng, T., Jiang, T., Zhang, B., Zhang, T., Dai, W., Yin, X., Li, Y., Wu, C., Wu, Y., Chi, X., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.26.591418 · Cited by 1 · see citing works
Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone ComplexPreprint
Hayward, R. E., Berkeley, R. F., Gao, Z., Garhammer, M., Morizono, M. A., Njomen, E., Li, H., DeMeester, K. E., Cociorva, V., Herzik, M. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.20.683548 · Cited by 1 · see citing works
A biased allosteric modulator functions as a molecular glue to induce β 2 AR dimerizationPreprint
Shen, J., Peddada, T., Komolov, K. E., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.21.683802 · Cited by 1 · see citing works
“Our findings extend the emerging paradigm of molecular glues in pharmacology 39,40 .”
Identification and SAR optimization of FBXO22-mediated TEAD Targeted Glue™ degradersPreprint
Fisher, M., Fletcher, A., Hamby, C., Miles, J., Ambler, M., Azevedo, A., Bisetto, S., Davies, C. T. R., Drouhin, P., Greger, L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.21.719895 · Cited by 1 · see citing works
Targeting proteins to lysosomes with a chemical inducer of arginine methylation
(2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01744-9
Small Molecule Drugs in Cancer Therapy
Beer, P. A., & Okkenhaug, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00135-6
The next frontier in drug discovery: Unveiling the pharmacological potential of proximity inducers
Holmberg‐Douglas, N., Keenan, K. N., de Turiso, F. G.-L., Chekler, E. P., Shanmugasundaram, V., Riggs, J. R., & Zapf, C. W. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00018-2
Reengineering of a Proteomimetic Pan‐Ras Inhibitor into a Ras Degrader
Ongkingco, J. F., Hong, S. H., Toth, E. D., Nguyễn, T. T., & Arora, P. S. (2025) · Angewandte Chemie · doi:10.1002/ange.202507092
Guarnaccia, A. D., Sandoval, W. N., & Lill, J. R. (2025) · doi:10.1002/9781394236145.ch1
Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders
Zhuang, Z., Byun, W. S., Kozicka, Z., Donovan, K. A., Dwyer, B. G., Thornhill, A. M., Jones, H. M., Jiang, Z., Zhu, X., Fischer, E. S., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202508427
Cyclic peptides as ligands for competition binding assays
van Neer, R. H. P., Dranchak, P. K., Davis, A. K., Rai, G., & Inglese, J. (2025) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2025.08.021
Progress on molecular glue degraders
Chen, J., Deng, Z., Li, H., & Liu, L. (2025) · Scientia Sinica Chimica · doi:10.1360/ssc-2025-0228
Verhoef, C. J. A., Crowe, C., Nakasone, M. A., Basté, A. D. L. C., Harzing, T., Span, N. A. S., Sathe, G. J., Iso, K., Ottmann, C., Brunsveld, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.17.688825
Pennings, M. A. M., van den Bosch, M. A. W., Oberheide, A., Verhoef, C. J. A., Ottmann, C., Markvoort, A. J., Miley, G. P., & Brunsveld, L. (2025) · Angewandte Chemie · doi:10.1002/ange.202521678
Neo‐Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein
Kumari, P., Oum, Y. H., Miller, E. J., Qui, M., Du, Y., Mou, H., Singh, R. K., Fu, H., & Mo, X. (2026) · Angewandte Chemie · doi:10.1002/ange.202512791
Targeted Protein Degradation by Repurposing Transmembrane E3 Ubiquitin Ligases
Cui, J., Qu, Q., & Pan, M. (2026) · ChemBioChem · doi:10.1002/cbic.202500870
Cancer biology and the principles of targeted cancer drug discovery
Davies, A., Jones, G., Krishnan, S., Krishnamoorthy, M., Maruggi, M., Kaneda, M., & Marjon, K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00035-2
Pieńkowska, D. E., & Nowak, R. P. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02187-0
Induced proximity strategies for modulating immune checkpoints in cancer immunotherapy
Wang, W., Li, Y., Zhang, W. Q., Zhang, Y., Zhang, K., Zhang, X. T., & Wang, T. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.118963 · Cited by 1 · see citing works
From Serendipity to Rationality: Expanding Druggability by Molecular Glue Discovery
Heppner, D. E., Kang, C., & Xu, W. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01252
- Authors
- Schreiber, S. L.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Schreiber, Stuart L.
- ORCID
- Schreiber, Stuart L.
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 31
- Issue
- 6
- Pages
- 1050-1063
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- OpenAlex
- W4399491693
- Semantic Scholar
- bdf154bc8ee372bd5acec4d6a1562bb429223611
- Cited by
- 112
- References
- 76
- Citations by year
- 2026: 41 · 2025: 62 · 2024: 9
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell chemical biology (publishedVersion, cc-by-nc-nd)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- 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
- Keywords
- molecular glues, bifunctional molecules, induced proximity, protein-protein interaction, fusion protein, missense mutations, post-translational modification, drug screening
- MeSH terms
- Humans, Protein Processing, Post-Translational, Proteins, Mutation, Missense
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
