Evidence map›Paper›PMID 38940379›Full record

ArticlePharmacology research & perspectives2024

Preclinical evaluation of ELP-004 in mice.

Jamie L McCall, Werner J Geldenhuys, Lisa J Robinson, Michelle R Witt, Peter M Gannett, Björn C G Söderberg, Harry C Blair, Jonathan Soboloff, John B Barnett

Abstract read
In one paragraph

Article in Pharmacology research & perspectives, 2024. 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. Article
  2. Preclinical evaluation of ELP-004 in mice.Pharmacology research & perspectives · 2024
    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

9 authors.

Jamie L McCallDepartment of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA.ORCID https://orcid.org/0000-0001-5914-6336
Werner J GeldenhuysDepartment of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, West Virginia, USA.ORCID https://orcid.org/0000-0002-2405-376X
Lisa J RobinsonDepartment of Pathology, West Virginia School of Medicine, Morgantown, West Virginia, USA.ORCID https://orcid.org/0009-0008-0642-3318
Michelle R WittDepartment of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA.ORCID https://orcid.org/0000-0001-9483-8346
Peter M GannettCollege of Pharmacy, Nova Southeastern University, Ft. Lauderdale, Florida, USA.ORCID https://orcid.org/0000-0002-7859-5468
Björn C G SöderbergC. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia, USA.ORCID https://orcid.org/0000-0003-0395-0354
Harry C BlairDepartments of Pathology and Cell Biology, The Pittsburgh VA Medical Center and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-1152-3718
Jonathan SoboloffFels Cancer Institute for Personalized Medicine and Department of Cancer and Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0001-5192-1297
John B BarnettDepartment of Microbiology, Immunology, and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA.ORCID https://orcid.org/0000-0001-6547-2381

Funding

WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI Travis Salisbury · 2012 to 2026
$61.1M
WVU Flow Cytometry and Single Cell Core Facility (FCSCCF)P20GM121322 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Dominique Bollino · 2018 to 2026
$22.4M
Prevention of arthritis-induced bone erosion by inhibiting osteoclast differentiation by the haloanilide, N-Methyl DichloropropionanilineR42AR074812 · NIAMS · EXESALIBERO, INC. · PI BARNETT, JOHN B · 2019 to 2021
$1.7M
NIAMS NIH HHS R42 AR074812NIAMS NIH HHS R42AR074812NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P20GM103434NIGMS NIH HHS P20 GM121322NIGMS NIH HHS P30GM121322
6 · The paper itself

Abstract

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP-004 was non-mutagenic, did not induce chromosome aberrations, non-cardiotoxic, and had minimal off-target effects. Using in vitro hepatic systems, we found that ELP-004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP-004 inhibits osteoclast differentiation without suppressing overall T-cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.

Indexed as

OsteoclastsAdministration, OralAnimalsAntirheumatic AgentsCell DifferentiationDrug Evaluation, PreclinicalFemaleHumansMaleMiceMice, Inbred C57BLT-LymphocytesAntirheumatic AgentsCYP450metabolismmiceosteoclastpharmacokineticspreclinical

Identifiers

PMID38940379
PMCPMC11212004

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.