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Review

Molecular glue degraders: exciting opportunities for novel drug discovery

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 433-449 | Received 06 Oct 2023, Accepted 15 Jan 2024, Published online: 24 Jan 2024

References

  • Cooper GM. Protein Degradation. In: The cell: a molecular approach. 2nd ed. [Internet]. Sinauer Associates;2000. [cited 2023 Nov 20]. Available from. https://www.ncbi.nlm.nih.gov/books/NBK9957/
  • Brehme M, Sverchkova A, Voisine C. Proteostasis network deregulation signatures as biomarkers for pharmacological disease intervention. Curr Opin Syst Biol. 2019;15:74–81. doi: 10.1016/j.coisb.2019.03.008
  • Balch WE, Morimoto RI, Dillin A, et al. Adapting proteostasis for disease intervention. Science. 2008;319(5865):916–919. doi: 10.1126/science.1141448
  • Yang N, Kong B, Zhu Z, et al. Recent advances in targeted protein degraders as potential therapeutic agents. Mol Divers [Internet]. 2023. [cited 2023 Nov 24]; Available from. doi: 10.1007/s11030-023-10606-w
  • PASSMORE LA, BARFORD D. Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochem J. 2004;379(3):513–525. doi: 10.1042/bj20040198
  • Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67(1):425–479. doi: 10.1146/annurev.biochem.67.1.425
  • Protacs: chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation. PNAS [Internet]. [cited 2023 Sep 27. Available from: https://www.pnas.org/doi/full/10.1073/pnas.141230798
  • Takahashi D, Moriyama J, Nakamura T, et al. Autacs: cargo-specific degraders using Selective autophagy. Molecular Cell. 2019;76(5):797–810.e10. doi: 10.1016/j.molcel.2019.09.009
  • Banik SM, Pedram K, Wisnovsky S, et al. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature. 2020;584(7820):291–297. doi: 10.1038/s41586-020-2545-9
  • Naito M, Ohoka N, Shibata N. Snipers—hijacking IAP activity to induce protein degradation. Drug Discovery Today. 2019;31:35–42. doi: 10.1016/j.ddtec.2018.12.002
  • Raina K, Forbes CD, Stronk R, et al. Regulated induced proximity targeting chimeras (RIPTACs): a novel heterobifunctional small molecule therapeutic strategy for killing cancer cells selectively. bioRxiv [Preprint]. 2023Jan 2. doi: 10.1101/2023.01.01.522436
  • Costales MG, Matsumoto Y, Velagapudi SP, et al. Small Molecule Targeted Recruitment of a Nuclease to RNA. J Am Chem Soc. 2018;140(22):6741–6744. doi: 10.1021/jacs.8b01233
  • Yamazoe S, Tom J, Fu Y, et al. Heterobifunctional molecules induce dephosphorylation of kinases-A proof of concept study. J Med Chem. 2020;63:2807–2813. doi: 10.1021/acs.jmedchem.9b01167
  • Reynders M, Matsuura BS, Bérouti M, et al. PHOTACs enable optical control of protein degradation. Sci Adv. 2020;6(8):eaay5064. doi: 10.1126/sciadv.aay5064
  • Neklesa TK, Tae HS, Schneekloth AR, et al. Small-molecule hydrophobic tagging–induced degradation of HaloTag fusion proteins. Nat Chem Biol. 2011;7(8):538–543. doi: 10.1038/nchembio.597
  • Hannah J, Zhou P. A small-molecule SMASh hit. Nat Chem Biol. 2015;11(9):637–638. doi: 10.1038/nchembio.1886
  • Kozicka Z, Thomä NH. Haven’t got a glue: protein surface variation for the design of molecular glue degraders. Cell Chem Biol. 2021;28:1032–1047. doi: 10.1016/j.chembiol.2021.04.009
  • Schreiber SL. Immunophilin-sensitive protein phosphatase action in cell signaling pathways. Cell. 1992;70(3):365–368. doi: 10.1016/0092-8674(92)90158-9
  • Tan X, Calderon-Villalobos LIA, Sharon M, et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature. 2007;446(7136):640–645. doi: 10.1038/nature05731
  • Tal L, Gil MXA, Guercio AM, et al. Structural aspects of plant hormone signal perception and regulation by ubiquitin ligases. Plant Physiol. 2020;182(4):1537–1544. doi: 10.1104/pp.19.01282
  • Calderon-Villalobos LI, Tan X, Zheng N, et al. Auxin perception—structural insights. Cold Spring Harb Perspect Biol. 2010;2:a005546. doi: 10.1101/cshperspect.a005546
  • Chini A, Fonseca S, Fernández G, et al. The JAZ family of repressors is the missing link in jasmonate signalling. Nature. 2007;448(7154):666–671. doi: 10.1038/nature06006
  • Fischer ES, Böhm K, Lydeard JR, et al. Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide. Nature. 2014;512(7512):49–53. doi: 10.1038/nature13527
  • Lenz W, Knapp K. Thalidomide Embryopathy. Arch Environ Health. 1962;5:14–19.
  • Research C for DE and. Thalidomide (marketed as thalomid) information. FDA [Internet]. 2018 [cited 2023 Sep 28]. Available from: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/thalidomide-marketed-thalomid-information
  • Vargesson N, Stephens T. Thalidomide: history, withdrawal, renaissance, and safety concerns. Expert Opin Drug Saf. 2021;20(12):1455–1457. doi: 10.1080/14740338.2021.1991307
  • Ito T, Ando H, Suzuki T, et al. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345–1350. doi: 10.1126/science.1177319
  • Chamberlain PP, Lopez-Girona A, Miller K, et al. Structure of the human cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat Struct Mol Biol. 2014;21(9):803–809. doi: 10.1038/nsmb.2874
  • Krönke J, Udeshi ND, Narla A, et al. Lenalidomide causes Selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343(6168):301–305. doi: 10.1126/science.1244851
  • Gandhi AK, Kang J, Havens CG, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN.). Br J Haematol. 2014;164:811–821. doi: 10.1111/bjh.12708
  • Lee H. Moffitt cancer center and research institute. A phase II biomarker trial of avadomide (CC-122) in combination with nivolumab in advanced melanoma [internet].clinicaltrials.gov; 2022 [cited 2023 Jan 1]. Report No.: NCT03834623. Available from: https://clinicaltrials.gov/study/NCT03834623
  • Petzold G, Fischer ES, Thomä NH. Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase. Nature. 2016;532(7597):127–130. doi: 10.1038/nature16979
  • Sievers QL, Petzold G, Bunker RD, et al. Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science. 2018;362(6414):eaat0572. doi: 10.1126/science.aat0572
  • Sasso JM, Tenchov R, Wang D, et al. Molecular glues: the adhesive connecting targeted protein degradation to the clinic. Biochemistry. 2022;62:601–623. doi: 10.1021/acs.biochem.2c00245
  • Golovin D, Biocentury . Ambagon: creating molecular glues for disordered proteins. 2022 [cited 2024 Jan 22]. Available from: https://www.biocentury.com/article/641999/ambagon-creating-molecular-glues-for-disordered-proteins
  • Liu S, Tong B, Mason JW, et al. Rational screening for cooperativity in small-molecule inducers of protein-protein associations. J Am Chem Soc. 2023;145:23281–23291. doi: 10.1021/jacs.3c08307
  • Hughes SJ, Ciulli A. Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders. Essays Biochem. 2017;61:505–516. doi: 10.1042/EBC20170041
  • Baek K, Schulman BA. Molecular glue concept solidifies. Nat Chem Biol. 2020;16(1):2–3. doi: 10.1038/s41589-019-0414-3
  • Han T, Goralski M, Gaskill N, et al. Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science. 2017;356(6336):eaal3755. doi: 10.1126/science.aal3755
  • Ting TC, Goralski M, Klein K, et al. Aryl sulfonamides degrade RBM39 and RBM23 by recruitment to CRL4-DCAF15. Cell Rep. 2019;29(6):1499–1510.e6. doi: 10.1016/j.celrep.2019.09.079
  • Faust TB, Yoon H, Nowak RP, et al. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat Chem Biol. 2020;16(1):7–14. doi: 10.1038/s41589-019-0378-3
  • Uehara T, Minoshima Y, Sagane K, et al. Selective degradation of splicing factor CAPERα by anticancer sulfonamides. Nat Chem Biol. 2017;13(6):675–680. doi: 10.1038/nchembio.2363
  • Gracias D, Moison C, Mendoza-Sanchez R, et al. Identification of a novel cyclin K degrader molecule with selective anti-AML activity. Blood. 2022;140(Supplement 1):10684. doi: 10.1182/blood-2022-166517
  • Houles T, Boucher J, Lavoie G, et al. The CDK12 inhibitor SR-4835 functions as a molecular glue that promotes cyclin K degradation in melanoma [Internet]. bioRxiv; 2023 [cited 2023 Sep 27].2023–2025. Available from: https://www.biorxiv.org/content/10.1101/2023.05.30.542844v1
  • Tan Q, Liu Z, Gao X, et al. Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors. Oncogene. 2022;41(42):4754–4767. doi: 10.1038/s41388-022-02467-8
  • Ling X, Xu C, Fan C, et al. FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX. Cancer Res. 2014;74(24):7487–7497. doi: 10.1158/0008-5472.CAN-14-0683
  • Bellenie BR, Cheung K-M, Varela A, et al. Achieving in vivo target depletion through the discovery and optimization of benzimidazolone BCL6 degraders. J Med Chem. 2020;63:4047–4068. doi: 10.1021/acs.jmedchem.9b02076
  • Gavory G, Ghandi M, Laine A-L, et al. Identification of MRT-2359, a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader (MGD) for the treatment of cancers with MYC-induced translational addiction. AACR Annual Meeting; New Orleans; April 8–13; 2022. Abstract 3929. doi: 10.1158/1538-7445.AM2022-3929
  • Monte rosa therapeutics advances second development candidate, MRT-6160, a novel, highly selective molecular glue degrader targeting VAV1 for the treatment of autoimmune diseases [internet]. BioSpace. [cited 2023 Nov 20]. Available from. https://www.biospace.com/article/monte-rosa-therapeutics-advances-second-development-candidate-mrt-6160-a-novel-highly-selective-molecular-glue-degrader-targeting-vav1-for-the-treatment-of-autoimmune-diseases/
  • Du X, Volkov OA, Czerwinski RM, et al. Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820. Structure. 2019;27(11):1625–1633.e3. doi: 10.1016/j.str.2019.10.005
  • Fischer T, Gazzola S, Riedl R. Approaching target selectivity by De novo drug design. Expert Opin Drug Discov. 2019;14(8):791–803. doi: 10.1080/17460441.2019.1615435
  • Tropsha A. QSAR in drug discovery. Drug design: structure- and ligand-based approaches. 1st ed. Cambridge (UK): Cambridge University Press; 2010. p. 151–164.
  • Lin S-K. Pharmacophore perception, development and use in drug design. In: Güner OF, editor. Molecules. Vol. 5. Lajolla, CA: mdpi; 2000. p. 987–989.
  • Furihata H, Yamanaka S, Honda T, et al. Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide. Nat Commun. 2020;11(1):4578. doi: 10.1038/s41467-020-18488-4
  • Hagner PR, Man H-W, Fontanillo C, et al. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood. 2015;126(6):779–789. doi: 10.1182/blood-2015-02-628669
  • Santiesteban DY, Duncan AD, Mirza NQ, et al. SP-3164, a novel cereblon-binding protein degrader, shows activity in preclinical lymphoma models. Blood. 2022;140(Supplement 1):8865–8866. doi: 10.1182/blood-2022-167495
  • Matyskiela ME, Lu G, Ito T, et al. A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase. Nature. 2016;535(7611):252–257. doi: 10.1038/nature18611
  • Hansen JD, Correa M, Alexander M, et al. CC-90009: a cereblon E3 ligase modulating drug that promotes selective degradation of GSPT1 for the treatment of acute myeloid leukemia. J Med Chem. 2021;64(4):1835–1843. doi: 10.1021/acs.jmedchem.0c01489
  • Chang Y, Keramatnia F, Ghate PS, et al. The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia. Blood. 2023;142(7):629–642. doi: 10.1182/blood.2022017813
  • Hansen JD, Correa M, Nagy MA, et al. Discovery of CRBN E3 ligase modulator CC-92480 for the treatment of relapsed and refractory multiple myeloma. J Med Chem. 2020;63(13):6648–6676. doi: 10.1021/acs.jmedchem.9b01928
  • Matyskiela ME, Zhang W, Man H-W, et al. A cereblon modulator (CC-220) with improved degradation of ikaros and Aiolos. J Med Chem. 2018;61(2):535–542. doi: 10.1021/acs.jmedchem.6b01921
  • Gemechu Y, Millrine D, Hashimoto S, et al. Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs. Proc Natl Acad Sci USA. 2018;115(46):11802–11807. doi: 10.1073/pnas.1814446115
  • Matyskiela ME, Zhu J, Baughman JM, et al. Cereblon modulators target ZBTB16 and its oncogenic fusion partners for degradation via distinct structural degrons. ACS Chem Biol. 2020;15(12):3149–3158. doi: 10.1021/acschembio.0c00674
  • Powell CE, Du G, Che J, et al. Selective degradation of GSPT1 by cereblon modulators identified via a focused combinatorial library. ACS Chem Biol. 2020;15(10):2722–2730. doi: 10.1021/acschembio.0c00520
  • Huber AD, Li Y, Lin W, et al. SJPYT-195: a designed nuclear receptor degrader that functions as a molecular glue degrader of GSPT1. ACS Med Chem Lett. 2022;13(8):1311–1320. doi: 10.1021/acsmedchemlett.2c00223
  • Bonazzi S, d’Hennezel E, Beckwith REJ, et al. Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy. Cell Chem Biol. 2023;30:235–247.e12. doi: 10.1016/j.chembiol.2023.02.005
  • Xie H, Li C, Tang H, et al. Development of substituted Phenyl Dihydrouracil as the novel achiral cereblon ligands for targeted protein degradation. J Med Chem. 2023;66(4):2904–2917. doi: 10.1021/acs.jmedchem.2c01941
  • Jarusiewicz JA, Yoshimura S, Mayasundari A, et al. Phenyl Dihydrouracil: an alternative Cereblon Binder for PROTAC design. ACS Med Chem Lett. 2023;14(2):141–145. doi: 10.1021/acsmedchemlett.2c00436
  • Shergalis AG, Marin VL, Rhee DY, et al. CRISPR Screen Reveals BRD2/4 molecular glue-like degrader via recruitment of DCAF16. ACS Chem Biol. 2023;18(2):331–339. doi: 10.1021/acschembio.2c00747
  • Thomas E, Thankan RS, Purushottamachar P, et al. Murine toxicology and pharmacokinetics of lead next generation galeterone analog, VNPP433-3β. Steroids. 2023;192:109184. doi: 10.1016/j.steroids.2023.109184
  • Xu Y, Yu Q, Wang P, et al. A selective small-molecule c-myc degrader potently regresses lethal c-myc overexpressing tumors. Adv Sci. 2022;9:e2104344. doi: 10.1002/advs.202104344
  • Heim C, Spring A-K, Kirchgäßner S, et al. Identification and structural basis of C-terminal cyclic imides as natural degrons for cereblon. Biochem Biophys Res Commun. 2022;637:66–72. doi: 10.1016/j.bbrc.2022.11.001
  • Krasavin M, Adamchik M, Bubyrev A, et al. Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor cereblon (CRBN): investigation of their binding mode and antiproliferative effects against myeloma cell lines. Eur J Med Chem. 2023;246:114990. doi: 10.1016/j.ejmech.2022.114990
  • Höglund P, Eriksson T, Björkman S. A double-blind study of the sedative effects of the thalidomide enantiomers in humans. J Pharmacokinet Biopharm. 1998;26(4):363–383. doi: 10.1023/A:1021008016719
  • Reist M, Carrupt P-A, Francotte E, et al. Chiral inversion and hydrolysis of thalidomide: mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites. Chem Res Toxicol. 1998;11(12):1521–1528. doi: 10.1021/tx9801817
  • Oleinikovas V, Gainza P, Ryckmans T, et al. From thalidomide to rational molecular glue design for targeted protein degradation. Annu Rev Pharmacol Toxicol. 2024;64(1):null. doi: 10.1146/annurev-pharmtox-022123-104147
  • Li W, Bengtson MH, Ulbrich A, et al. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling. PLoS One. 2008;3:e1487. doi: 10.1371/journal.pone.0001487
  • Ichikawa S, Flaxman HA, Xu W, et al. The E3 ligase adapter cereblon targets the C-terminal cyclic imide degron. Nature. 2022;610(7933):775–782. doi: 10.1038/s41586-022-05333-5
  • Walsh CT, Garneau-Tsodikova S, Gatto GJ. Protein posttranslational modifications: the chemistry of proteome diversifications. Angew Chem Int Ed Engl. 2005;44(45):7342–7372. doi: 10.1002/anie.200501023
  • Semenza GL. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE. 2007;2007:cm8. doi: 10.1126/stke.4072007cm8
  • Simonetta KR, Taygerly J, Boyle K, et al. Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction. Nat Commun. 2019;10(1):1402. doi: 10.1038/s41467-019-09358-9
  • Jung J, Park J, Mohanty S, et al. PIN-A1, a novel casein kinase 1α-selective molecular glue degrader, demonstrates strong antitumor activity via activation of the p53 pathway in preclinical models of AML with a favorable safety profile. Eur J Cancer. 2022;174:S20. doi: 10.1016/S0959-8049(22)00857-7
  • Mutlu M, Schmidt I, Morrison AI, et al. A novel HERC4-dependent glue degrader targeting STING [internet]. bioRxiv; 2023 [cited 2023 Sep 29]. p. 2023.02.08.527642. Available from: https://www.biorxiv.org/content/10.1101/2023.02.08.527642v1
  • Okada Y, Murayama N, Yanagida C, et al. Drug interactions of thalidomide with midazolam and cyclosporine A: heterotropic cooperativity of human cytochrome P450 3A5. Drug Metab Dispos. 2009;37(1):18–23. doi: 10.1124/dmd.108.024679
  • Hartmann MD, Boichenko I, Coles M, et al. Thalidomide mimics uridine binding to an aromatic cage in cereblon. J Struct Biol. 2014;188(3):225–232. doi: 10.1016/j.jsb.2014.10.010
  • Erlanson DA, McDowell RS, O’Brien T. Fragment-based drug discovery. J Med Chem. 2004;47(14):3463–3482. doi: 10.1021/jm040031v
  • Arkin MR, Wells JA. Small-molecule inhibitors of protein–protein interactions: progressing towards the dream. Nat Rev Drug Discov. 2004;3(4):301–317. doi: 10.1038/nrd1343
  • Wu H, Yao H, He C, et al. Molecular glues modulate protein functions by inducing protein aggregation: a promising therapeutic strategy of small molecules for disease treatment. Acta Pharm Sin B. 2022;12(9):3548–3566. doi: 10.1016/j.apsb.2022.03.019
  • Guharoy M, Bhowmick P, Sallam M, et al. Tripartite degrons confer diversity and specificity on regulated protein degradation in the ubiquitin-proteasome system. Nat Commun. 2016;7(1):10239. doi: 10.1038/ncomms10239
  • Wang Z-Z, Shi X-X, Huang G-Y, et al. Fragment-based drug discovery supports drugging “undruggable” protein-protein interactions. Trends Biochem Sci. 2023;48:539–552. doi: 10.1016/j.tibs.2023.01.008
  • Michaelides IN, Collie GW. E3 ligases meet their match: fragment-based approaches to discover new E3 ligands and to unravel E3 biology. J Med Chem. 2023;66(5):3173–3194. doi: 10.1021/acs.jmedchem.2c01882
  • Resnick E, Bradley A, Gan J, et al. Rapid covalent-probe discovery by electrophile-fragment screening. J Am Chem Soc. 2019;141(22):8951–8968. doi: 10.1021/jacs.9b02822
  • Backus KM, Correia BE, Lum KM, et al. Proteome-wide covalent ligand discovery in native biological systems. Nature. 2016;534(7608):570–574. doi: 10.1038/nature18002
  • QuEEN [Internet]. Monte Rosa Therapeutics. [cited 2023 Sep 27]. Available from: https://www.monterosatx.com/queen/
  • Ng A, Offensperger F, Cisneros JA, et al. Discovery of molecular glue degraders via isogenic morphological profiling. ACS Chem Biol. 2023 [cited 2023 Nov 22]; Available from;18(12):2464–2473. https://pubs.acs.org/doi/abs/10.1021/acschembio.3c00598
  • Mayor-Ruiz C, Bauer S, Brand M, et al. Rational discovery of molecular glue degraders via scalable chemical profiling. Nat Chem Biol. 2020;16(11):1199–1207. doi: 10.1038/s41589-020-0594-x
  • Hanzl A, Barone E, Bauer S, et al. E3-specific degrader discovery by dynamic tracing of substrate receptor abundance. J Am Chem Soc. 2023;145(2):1176–1184. doi: 10.1021/jacs.2c10784
  • King EA, Cho Y, Hsu NS, et al. Chemoproteomics-enabled discovery of a covalent molecular glue degrader targeting NF-κB. Cell Chem Biol. 2023;30(4):394–402.e9. doi: 10.1016/j.chembiol.2023.02.008
  • Weiss DR, Bortolato A, Sun Y, et al. On ternary complex stability in protein degradation: In Silico molecular glue binding affinity calculations. J Chem Inf Model. 2023 [cited 2023 Apr 12]; Available from;63(8):2382–2392. doi: 10.1021/acs.jcim.2c01386
  • Tao AJ, Jiang J, Gadbois GE, et al. A biotin targeting chimera (BioTAC) system to map small molecule interactomes in situ. bioRxiv [Preprint]. 2023 [cited 2024 Jan 22].doi: 10.1101/2023.08.21.554211
  • Huang Y, Li Y, Li X. Strategies for developing DNA-encoded libraries beyond binding assays. Nat Chem. 2022;14(2):129–140. doi: 10.1038/s41557-021-00877-x
  • Mason JW, Hudson L, Westphal MV, et al. DNA-encoded library (DEL)-enabled discovery of proximity-inducing small molecules [internet]. bioRxiv; 2022 [cited 2023 Sep 27]. 2022.10.13.512184. Available from: https://www.biorxiv.org/content/10.1101/2022.10.13.512184v1
  • Disch JS, Duffy JM, Lee ECY, et al. Bispecific Estrogen Receptor α degraders incorporating novel binders identified using DNA-Encoded chemical library screening. J Med Chem. 2021;64(8):5049–5066. doi: 10.1021/acs.jmedchem.1c00127
  • Toriki ES, Papatzimas JW, Nishikawa K, et al. Rational chemical design of Molecular Glue degraders. ACS Cent Sci. 2023;9(5):915–926. doi: 10.1021/acscentsci.2c01317
  • Morreale FE, Kleine S, Leodolter J, et al. BacPROTACs mediate targeted protein degradation in bacteria. Cell. 2022;185(13):2338–2353.e18. doi: 10.1016/j.cell.2022.05.009
  • Ahmad H, Zia B, Husain H, et al. Recent advances in PROTAC-Based antiviral strategies. Vaccines. 2023;11(2):270. doi: 10.3390/vaccines11020270
  • Liang J, Wu Y, Lan K, et al. Antiviral PROTACs: opportunity borne with challenge. Cell Insight. 2023;2(3):100092. doi: 10.1016/j.cellin.2023.100092
  • Danazumi AU, Ishmam IT, Idris S, et al. Targeted protein degradation might present a novel therapeutic approach in the fight against African trypanosomiasis. Eur J Pharmaceut Sci. 2023;186:106451. doi: 10.1016/j.ejps.2023.106451
  • Li F, Aljahdali IAM, Ling X. Molecular glues: capable protein-binding small molecules that can change protein–protein interactions and interactomes for the potential treatment of human cancer and neurodegenerative diseases. IJMS. 2022;23:6206. doi: 10.3390/ijms23116206
  • Alabi S. Novel mechanisms of molecular glue-induced protein degradation. Biochemistry. 2021;60(31):2371–2373.
  • Shah VJ, Đikić I. Localization matters in targeted protein degradation. Cell Chem Biol. 2022;29(10):1465–1466. doi: 10.1016/j.chembiol.2022.09.006

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