Evidence map›Paper›PMID 42845394›Full record

ArticlebioRxiv : the preprint server for biology2026

TR-107, a novel mitochondrial ClpP agonist, induces robust antitumor activity against preclinical models of adrenocortical carcinoma.

George I Karadimov, Yoo Sun Kim, Haiqing Fu, Sidhant Narula, Fathi Elloumi, Anjali Dhall, Frank Echtenkamp, Luowei Li, Edwin J Iwanowicz, Lee M Graves and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

George I KaradimovDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0009-0006-4095-0141
Yoo Sun KimDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Haiqing FuDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Sidhant NarulaDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Fathi ElloumiDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Anjali DhallDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Frank EchtenkampUrologic Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Luowei LiLaboratory of Cancer Biology and Genetics, Center for Cancer Research, NCI, Bethesda, MD, USA.
Edwin J IwanowiczMadera Therapeutics LLC, Chapel Hill, NC, USA.
Lee M GravesMadera Therapeutics LLC, Chapel Hill, NC, USA.
King ChanProtein and Metabolite Characterization Core, Center for Cancer Research, NCI, Frederick, MD, USA.
Thorkell AndressonProtein and Metabolite Characterization Core, Center for Cancer Research, NCI, Frederick, MD, USA.
Robert W RobeyLaboratory of Cell Biology, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0002-0857-3650
Yoshimi GreerWomen's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Stanley LipkowitzWomen's Malignancies Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0002-6103-2255
Chuong D HoangThoracic Surgery Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Jonathan M HernandezSurgical Oncology Program, Center for Cancer Research, NCI, Bethesda, MD, USA.
Yves PommierDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Mirit I AladjemDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID 0000-0002-1875-3110
Urbain WeyemiDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Myriem BoufraqechSurgical Oncology Program, Center for Cancer Research, NCI, Bethesda, MD, USA.
Suresh M KumarDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Jaydira Del RiveroDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy originating from the adrenal cortex with limited effective treatment options. The underlying pathophysiology of ACC is uniquely characterized by abnormal steroid production and increased metabolic activity, highlighting the critical role of mitochondria in adrenal steroid hormone biosynthesis and tumor metabolism. In this study, we investigated the therapeutic potential of TR-107, a novel and highly selective small-molecule agonist targeting the mitochondrial protease ClpP. Pharmacologic hyperactivation of ClpP disrupts mitochondrial proteostasis and bioenergetics and has shown promising antitumor activity in various preclinical models. Our results demonstrated that TR-107 induces potent dose-dependent cytotoxic effects at nanomolar concentrations in ACC cell lines NCI-H295R and mACC3 as well as short-term ACC patient-derived organoid (PDO) models, markedly reducing cell viability and confluency

Indexed as

Adrenocortical carcinomadevelopmental therapeuticsdrug synergymitochondriapatient-derived organoidsTR-107

Identifiers

PMID42845394
PMCPMC13640636

What OpenQuestion holds

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Registered trials

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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.