Evidence map›Paper›PMID 40922058›Full record

ArticleJournal of medicinal chemistry2025

Development of Macrocyclic Peptide-Based Proteasome Inhibitors with Enhanced Blood-Brain Barrier Penetration for Treating Brain Neoplasms.

Jehad Almaliti, Momen Al-Hindy, Pavla Fajtová, Evgenia Glukhov, Theodore Berger, Yan Graf, Cesar Emiliano Hoffmann da Silva, Chandler Huang, Narek Azizyan, Yuxian He and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

12 authors.

Jehad AlmalitiCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.ORCID 0000-0002-3562-0846
Momen Al-HindyCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Pavla FajtováSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.
Evgenia GlukhovCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Theodore BergerCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Yan GrafCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Cesar Emiliano Hoffmann da SilvaPharmaceutical Synthesis Group (PHARSG), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.ORCID 0000-0002-8153-1190
Chandler HuangCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Narek AzizyanCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.ORCID 0009-0005-8957-2172
Yuxian HeCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Anthony J O'DonoghueSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, United States.ORCID 0000-0001-5695-0409
William H GerwickCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.ORCID 0000-0003-1403-4458

Funding

Unified Computation Tools for Natural Products ResearchR01GM107550 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COTTRELL, GARRISON W, GERWICK, WILLIAM HENRY · 2013 to 2025
$8.2M
Proteasome inhibitors against mucosal protozoan pathogensR01AI158612 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS, O'DONOGHUE, ANTHONY JOHN · 2021 to 2025
$3.2M
New tools to facilitate drug discovery for pathogen proteasomesR21AI188258 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAFFREY, CONOR, O'DONOGHUE, ANTHONY JOHN · 2025 to 2025
$439k
The catalytic core of the proteasome as a drug target to treat Human African TrypanosomiasisR21AI171824 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAFFREY, CONOR, O'DONOGHUE, ANTHONY JOHN · 2022 to 2023
$435k
Selective proteasome inhibitors for trichomoniasisR21AI146387 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS, O'DONOGHUE, ANTHONY JOHN · 2019 to 2020
$433k
NIAID NIH HHS R01 AI158612NIAID NIH HHS R21 AI146387NIAID NIH HHS R21 AI171824NIAID NIH HHS R21 AI188258NIGMS NIH HHS R01 GM107550
6 · The paper itself

Abstract

Proteasome inhibitors are effective in treating hematologic cancers but have limited utility in brain tumors due to poor blood-brain barrier (BBB) penetration and metabolic instability. In this study, we developed novel macrocyclic peptide epoxyketone inhibitors with improved drug-like properties. Compounds were screened for cytotoxicity against brain cancer cell lines, permeability (PAMPA-BBB and Caco-2), and metabolic stability. Lead compound

Indexed as

Antineoplastic AgentsBlood-Brain BarrierBrain NeoplasmsMacrocyclic CompoundsPeptidesProteasome InhibitorsAnimalsCaco-2 CellsCell Line, TumorHumansMiceStructure-Activity RelationshipAntineoplastic AgentsMacrocyclic CompoundsPeptidesProteasome Inhibitors

Identifiers

PMID40922058
PMCPMC13626384

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.