ArticleCell communication and signaling : CCS2026
Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundThe heat shock protein 90 (HSP90) chaperone complex directs either the proper folding or proteasome-mediated degradation of its substrate proteins. Extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase family, has been implicated in the biology of several cancer types. To harness the protein-degradation activity of this HSP90 chaperone complex, we developed a novel targeted protein degradation technology, termed Chaperone-Mediated Protein Degradation (CHAMP), and an ERK5-CHAMP was designed to induce chemical proximity between HSP90 and ERK5 to induce ERK5 degradation.
methodsIn this study, potential degraders targeting ERK5, termed ERK5-CHAMPs, were developed. An ERK5-CHAMP was identified to degrade ERK5 protein via ubiquitin-proteasome system (UPS) by western blot in vitro and in vivo, and to reduce tumor growth in vitro by cell viability assay, FACS and in vivo by mouse xenograft models. The pharmacokinetic (PK) properties of ERK5-CHAMP were also tested through LC-MS. Moreover, immunofluorescence and a reporter system were used to explore the mechanism associated with ERK5-CHAMP.
resultsThe treatment of cancer cells with ERK5-CHAMP resulted in proteasome-dependent ERK5 degradation and prevented ERK5 nuclear accumulation. ERK5-CHAMP treatment led to cell cycle arrest, increased apoptosis, and reduced cell viability. in vivo, ERK5-CHAMP significantly reduced tumor growth in mouse xenograft tumor models and preferentially accumulated in tumors relative to levels in normal tissues. These data highlight the potential of CHAMP degraders targeting ERK5 for cancer treatment.
conclusionCHAMP is a novel, small-molecule targeted protein degradation technology. ERK5-CHAMP resulted in proteasome-dependent ERK5 degradation and hampered ERK5 nuclear accumulation, displayed tumor-selective pharmacokinetic properties and significantly reduced tumor growth. This suggests that ERK5-targeting CHAMPs represent a promising new approach to disrupt the entire function of ERK5 and could be exploited for cancer treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.