{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T19:03:04Z","timestamp":1779822184351,"version":"3.53.1"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002713","name":"Imam Mohammed Ibn Saud Islamic University","doi-asserted-by":"publisher","award":["IMSIU\u2010DDRSP2601"],"award-info":[{"award-number":["IMSIU\u2010DDRSP2601"]}],"id":[{"id":"10.13039\/501100002713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Protein\u2013protein interactions (PPIs) that orchestrate ubiquitin\u2010dependent signaling have long challenged drug discovery because their interfaces are typically large and hydrophobic. The heterodimeric adaptor Elongin BC (ELOB\/ELOC) defies this stereotype: its BC\u2010box\u2013binding groove is a deep, rigid pocket that anchors dozens of cellular and viral partners to cullin\u2010RING ligases and to transcriptional machinery. Recent structural and chemical\u2010biology breakthroughs have converted this once \u201cundruggable\u201d site into a tractable target. A sub\u2010nanomolar peptide derived from the chromatin factor EPOP has been shown to displace native BC\u2010box proteins, trigger apoptosis in multiple cancer lines, and unveil a transcriptomic signature that converges on MYC and cell\u2010cycle control. Parallel fragment screens and crystallography have mapped adjacent hot spots suitable for small\u2010molecule growth, while functional genomics highlights Elongin BC as a pan\u2010cancer dependency and an unexpected regulator of the SARS\u2010CoV\u20102 co\u2010receptor TMPRSS2. This review synthesizes the structural principles of BC\u2010box recognition, the current state of peptide and fragment\u2010based inhibitors, and the biological consequences of disrupting the Elongin BC hub. We discuss therapeutic prospects in oncology and virology, outline key challenges\u2014delivery, selectivity, and resistance\u2014and propose future directions ranging from stapled\u2010peptide optimization to covalent fragment tethering and PROTAC strategies. Together, these advances position Elongin BC inhibition at the forefront of next\u2010generation PPI drug discovery, offering a unified approach to modulate ubiquitin signaling, epigenetic regulation, and viral entry through a single conserved pocket.<\/jats:p>","DOI":"10.1111\/cbdd.70307","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:00:46Z","timestamp":1777860046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the Elongin\n                    <scp>BC<\/scp>\n                    \u2013\n                    <scp>BC<\/scp>\n                    \u2010Box Interface: Structural Insights, Peptidic Disruptors and Emerging Small\u2010Molecule Strategies"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-9564","authenticated-orcid":false,"given":"Emadeldin 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