{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:15Z","timestamp":1786390815014,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W006804\/1"],"award-info":[{"award-number":["MR\/W006804\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/y00364\/1"],"award-info":[{"award-number":["MR\/y00364\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Colorectal cancer is one of the most prevalent cancers worldwide, and novel precision medicine approaches are rapidly improving patient outcomes. Phosphodiesterase 4B (PDE4B) is a member of an enzyme family (PDE4) that hydrolyses intracellular cAMP to control spatial and temporal signalling cues. The PDE4B family, particularly PDE4B shortforms, has been implicated in the progression of colorectal cancer and has emerged as a novel drug target. However, clinically available PDE4 inhibitors are limited therapeutically by their active site\u2010directed action, which lacks subfamily selectivity, resulting in a broad range of adverse effects. Targeted protein degradation may provide a novel strategy for designing more potent and selective PDE4B blockers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>A novel proteolysis\u2010targeting chimaera (PROTAC) was studied to determine the effect of PDE4B shortform degradation on several hallmarks of cancer in the KRAS\u2010mutant cell line HCT116.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>We developed a novel PROTAC, KTX207, which selectively degrades PDE4B shortforms in HCT116 cells. KTX207 significantly increased cAMP levels and decreased PDE4 activity in HCT116 cells, relative to the effects of a small\u2010molecule PDE4 inhibitor at the same concentration. Furthermore, KTX207 decraesed cell migration and invasion, replicative immortality and angiogenic potential of HCT116 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>This research showed that the selective degradation of PDE4B shortform significantly improved attenuation of certain hallmarks of cultured colorectal cancer models. This novel therapeutic approach has greater potential than existing PDE4 inhibitors, as the potency\/selectivity we engineered into the PDE4 PROTAC may eliminate side\u2010effects exhibited by conventional PDE4 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70528","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:22:00Z","timestamp":1782876120000},"page":"5516-5540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The selective degradation of PDE4B shortform, using a PROTAC, leads to inhibition of several hallmarks of cancer in HCT116 cells"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5267-0514","authenticated-orcid":false,"given":"Alina","family":"Zorn","sequence":"first","affiliation":[{"name":"University of Glasgow  Glasgow 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