Evidence map›Paper›PMID 35625675›Full record

ArticleBiomedicines2022

Small Molecule 20S Proteasome Enhancer Regulates MYC Protein Stability and Exhibits Antitumor Activity in Multiple Myeloma.

Evert Njomen, Allison Vanecek, Theresa A Lansdell, Ya-Ting Yang, Peter Z Schall, Christi M Harris, Matthew P Bernard, Daniel Isaac, Omar Alkharabsheh, Anas Al-Janadi and 9 more

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 34% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 2 countries.

Evert NjomenDepartment of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Allison VanecekDepartment of Chemistry, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-8646-4468
Theresa A LansdellDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Ya-Ting YangComparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI 48824, USA.
Peter Z SchallComparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI 48824, USA.
Christi M HarrisDepartment of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Matthew P BernardDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Daniel IsaacBreslin Cancer Center and Clinical Center, Lansing, MI 48910, USA.
Omar AlkharabshehBreslin Cancer Center and Clinical Center, Lansing, MI 48910, USA.ORCID 0000-0002-5299-4233
Anas Al-JanadiBreslin Cancer Center and Clinical Center, Lansing, MI 48910, USA.ORCID 0000-0003-3531-6710
Matthew B GilettoDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Edmund EllsworthDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Catherine TaylorDepartment of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Terence TangDepartment of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Sarah LauDepartment of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Marc BailieDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Jamie J BernardDepartment of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Vilma Yuzbasiyan-GurkanComparative Medicine and Integrative Biology Program, Michigan State University, East Lansing, MI 48824, USA.
Jetze J TepeDepartment of Chemistry, Michigan State University, East Lansing, MI 48824, USA.
Michigan State University · USUniversity of Waterloo · CA

Funding

MULTIDISCIPLINARY TRAINING IN ENVIRONMENTAL TOXICOLOGYT32ES007255 · NIEHS · MICHIGAN STATE UNIVERSITY · PI JOHN J LAPRES · 1989 to 2026
$9.3M
International Myeloma Foundation Brian D. Novis GrantMichigan State University SPG and CTSIMichigan Translational Research and Commercialization (MTRAC) innovation hubNational Institute of Health 1R21AI117018-01A1National Institute of Health 5R01AG066223-02National Institute of Health T32GM092715NIEHS NIH HHS T32 ES007255
6 · The paper itself

Abstract

Despite the addition of several new agents to the armamentarium for the treatment of multiple myeloma (MM) in the last decade and improvements in outcomes, the refractory and relapsing disease continues to take a great toll, limiting overall survival. Therefore, additional novel approaches are needed to improve outcomes for MM patients. The oncogenic transcription factor MYC drives cell growth, differentiation and tumor development in many cancers. MYC protein levels are tightly regulated by the proteasome and an increase in MYC protein expression is found in more than 70% of all human cancers, including MM. In addition to the ubiquitin-dependent degradation of MYC by the 26S proteasome, MYC levels are also regulated in a ubiquitin-independent manner through the REGγ activation of the 20S proteasome. Here, we demonstrate that a small molecule activator of the 20S proteasome, TCH-165, decreases MYC protein levels, in a manner that parallels REGγ protein-mediated MYC degradation. TCH-165 enhances MYC degradation and reduces cancer cell growth in vitro and in vivo models of multiple myeloma by enhancing apoptotic signaling, as assessed by targeted gene expression analysis of cancer pathways. Furthermore, 20S proteasome enhancement is well tolerated in mice and dogs. These data support the therapeutic potential of small molecule-driven 20S proteasome activation for the treatments of MYC-driven cancers, especially MM.

Indexed as

chemotherapymultiple myelomaMYCnovel treatmentprotein degradationproteosome

Identifiers

PMID35625675
PMCPMC9138505
OpenAlexW4224231151

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.