ArticleACS medicinal chemistry letters2026
Identification of Clofibric Acid as a Synoviolin (SYVN1) Ligand for Proteolysis-Targeting Chimera (PROTAC) Development.
Julia Warren, Anandarao Munakala, Keith D Zientek, Kilsun Kim, Phillip A Wilmarth, Ashok P Reddy, Bingbing X Li, Xiangshu Xiao
Abstract read
In one paragraphArticle in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
8 authors.
Julia WarrenProgram in Chemical Biology, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Anandarao MunakalaProgram in Chemical Biology, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Keith D ZientekProteomics Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Kilsun KimProteomics Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Phillip A WilmarthProteomics Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Ashok P ReddyProteomics Shared Resources, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.
Bingbing X LiProgram in Chemical Biology, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.ORCID https://orcid.org/0000-0001-8259-9448 Xiangshu XiaoProgram in Chemical Biology, Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239, United States.ORCID https://orcid.org/0000-0001-9520-1371 Funding
Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Luiz Eduardo Bertassoni · 1997 to 2026
$60.5MProteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI TED S ACOTT · 1995 to 2026
$19.4MSmall molecules targeting RuvBL complex for triple negative breast cancerR01CA278058 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bingbing Li, Xiangshu Xiao · 2023 to 2026
$2.4MTargeting Hsp60 to Inhibit CREB-mediated Gene TranscriptionR01GM122820 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI XIAO, XIANGSHU · 2017 to 2023
$1.9MOrbitrap Tribrid Mass SpectrometerS10OD028533 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI DAVID, LARRY L · 2021 to 2021
$1.1MNCI NIH HHS P30 CA069533NCI NIH HHS R01 CA278058NEI NIH HHS P30 EY010572NIGMS NIH HHS R01 GM122820NIH HHS S10 OD028533
6 · The paper itselfAbstract
Targeted protein degradation (TPD) via proteolysis-targeting chimeras (PROTACs) is a powerful therapeutic strategy, yet only a small fraction of the >600 human E3 ligases have been harnessed. To expand this repertoire, we developed clickable photoaffinity probes based on clinically used drugs and metabolites to identify potential E3 ligases as targets. Here, we report the discovery of clofibric acid with a molecular weight of only 214 Da as a ligand for synoviolin (SYVN1). We demonstrate its utility by developing clofibric acid-based BRD4 PROTACs. The linker length and architecture play a critical role in the target degradation efficiency. The clofibric acid-derived BRD4 PROTACs achieve selective BRD4 degradation in an SYVN1-dependent manner. Our findings establish clofibric acid as a robust addition to the TPD toolbox, offering a novel E3 ligase recruitment strategy for the development of next-generation degraders.
Indexed as
chemoproteomics, degradationclofibric acidE3 ligasePROTACSYVN1
Identifiers
PMID42445038
PMCPMC13358943
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