Evidence map›Paper›PMID 39689856›Full record

ArticleOpen biology2024

Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Anuradha F Lingappa, Olayemi Akintunde, Erin Samueli, Connie Ewald, Maya Michon, Niloufar Ziari, Ming Lu, Shao Feng Yu, Markus Froehlich, Phuong Uyen Le and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Open biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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

30 authors.

Anuradha F LingappaProsetta Biosciences, San Francisco, CA, USA.
Olayemi AkintundeProsetta Biosciences, San Francisco, CA, USA.
Erin SamueliProsetta Biosciences, San Francisco, CA, USA.
Connie EwaldProsetta Biosciences, San Francisco, CA, USA.
Maya MichonProsetta Biosciences, San Francisco, CA, USA.
Niloufar ZiariProsetta Biosciences, San Francisco, CA, USA.
Ming LuUniversity of California San Francisco, San Francisco, CA, USA.
Shao Feng YuProsetta Biosciences, San Francisco, CA, USA.
Markus FroehlichProsetta Biosciences, San Francisco, CA, USA.
Phuong Uyen LeSunnybrook Research Institute, Toronto, ON, Canada.
Yuniel FernandezSunnybrook Research Institute, Toronto, ON, Canada.
Suguna MalleshProsetta Biosciences, San Francisco, CA, USA.
Jim LinProsetta Biosciences, San Francisco, CA, USA.
Anatoliy KitaygorodskyyProsetta Biosciences, San Francisco, CA, USA.
Dennis SolasProsetta Biosciences, San Francisco, CA, USA.
Jonathan C ReedDepartment of Global Health, University of Washington, Seattle, WA, USA.
Jaisri R LingappaDepartment of Global Health, University of Washington, Seattle, WA, USA.
Andreas Müller-SchiffmannInstitute of Neuropathology, Heinrich Heine University, Dusseldorf, Germany.
Carsten KorthInstitute of Neuropathology, Heinrich Heine University, Dusseldorf, Germany.
Dharma PrasadProsetta Biosciences, San Francisco, CA, USA.
Aysegul NalcaUnited States Army Medical Research Institute for Infectious Diseases, Frederick, MD, USA.
Emily AstonTechAccel, Overland Park, KS, USA.
Brad FabbriTechAccel, Overland Park, KS, USA.
Sanjeev K AnandModulant Biosciences, Fishers, IN, USA.
Thomas W CampiModulant Biosciences, Fishers, IN, USA.
Emma PetrouskiProsetta Biosciences, San Francisco, CA, USA.
Debendranath DeyProsetta Biosciences, San Francisco, CA, USA.
David W AndrewsSunnybrook Research Institute, Toronto, ON, Canada.
James L RubensteinUniversity of California San Francisco, San Francisco, CA, USA.
Vishwanath R LingappaProsetta Biosciences, San Francisco, CA, USA.ORCID 0000-0003-0962-6571

Funding

Optical Systems for In Vivo Molecular Imaging of CancerR01CA103830 · NCI · UNIVERSITY OF TEXAS AUSTIN · PI RICHARDS-KORTUM, REBECCA R. · 2004 to 2015
$12.4M
CIHRLeukemia and Lymphoma Society of CanadaNCI NIH HHS R01 CA103830NIH HHSProsetta Biosciences Inc
6 · The paper itself

Abstract

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations. Anti-tumour properties of both chemotypes were validated in mouse xenografts against A549 human lung cancer and, for one of the chemotypes, against HT-29 colorectal cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex. Treatment with these compounds alters the target multi-protein complexes in a manner that appears to remove a block, crucial for cancer survival and progression, on a homeostatic linkage between uncontrolled proliferation and apoptosis. These compounds provide starting points for development of novel, next-generation, non-toxic, pan-cancer therapeutics.

Indexed as

Antineoplastic AgentsA549 CellsAnimalsAntiviral AgentsApoptosisCell Line, TumorCell ProliferationHIVHT29 CellsHumansMiceMonkeypox virusNeoplasmsSmall Molecule LibrariesXenograft Model Antitumor AssaysAntineoplastic AgentsAntiviral AgentsSmall Molecule Librariesallosteric modulatordrug discoverymulti-protein complexpan-cancer therapeuticsrestoration of homeostasis

Identifiers

PMID39689856
PMCPMC11651915

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.