Evidence map›Paper›PMID 35664983›Full record

ArticleSkin health and disease2021

Preclinical assessment of dual CYP26[A1/B1] inhibitor, DX308, as an improved treatment for keratinization disorders.

J G S Veit, Y Poumay, D Mendes, J Kreitinger, L Walker, A Paquet, C Menigot, F Zolezzi, A S Paller, P Diaz

Open access · goldAbstract read
In one paragraph

Article in Skin health and disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 52% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

10 authors at 4 institutions in 2 countries.

J G S VeitDepartment of Biomedical and Pharmaceutical Sciences University of Montana Missoula Montana USA.ORCID https://orcid.org/0000-0001-5908-0648
Y PoumayURPHYM-NARILIS University of Namur Namur Belgium.ORCID https://orcid.org/0000-0001-5200-3367
D MendesR&D DermaXon LLC Missoula Montana USA.ORCID https://orcid.org/0000-0003-4887-8122
J KreitingerR&D DermaXon LLC Missoula Montana USA.ORCID https://orcid.org/0000-0003-0341-7429
L WalkerR&D DermaXon LLC Missoula Montana USA.ORCID https://orcid.org/0000-0002-6158-5490
A PaquetSyneos Health Biot France.ORCID https://orcid.org/0000-0001-8669-1495
C MenigotSyneos Health Biot France.ORCID https://orcid.org/0000-0002-6028-0281
F ZolezziSyneos Health Biot France.ORCID https://orcid.org/0000-0002-8410-1401
A S PallerDepartment of Dermatology Northwestern University Feinberg School of Medicine Chicago Illinois USA.ORCID https://orcid.org/0000-0001-6187-6549
P DiazDepartment of Biomedical and Pharmaceutical Sciences University of Montana Missoula Montana USA.ORCID https://orcid.org/0000-0002-2339-8803
University of Montana · USSyneos Health (United States) · USUniversity of Namur · BENorthwestern University · US

Funding

Surveillance genome sequencing to detect SARS-CoV-2 virus variants in MontanaP20GM103546 · NIGMS · UNIVERSITY OF MONTANA · PI BOWLER, BRUCE E · 2012 to 2021
$19.2M
Northwestern University Skin Disease Research Center Resource-based CenterP30AR075049 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Irina Budunova · 2019 to 2026
$6.6M
Selective inhibition of CYP26A1 in the skin for the treatment of ichthyosisR44AR069416 · NIAMS · DERMAXON, LLC · PI ASTRUC DIAZ, FANNY · 2018 to 2019
$1.5M
NIAMS NIH HHS P30 AR075049NIAMS NIH HHS R44 AR069416NIGMS NIH HHS P20 GM103546
6 · The paper itself

Abstract

Background: Retinoid-based therapies are commonly used in the treatment of disorders of keratinization and other skin disorders but can result in non-specific effects and adverse reactions. Use of retinoic acid metabolism blocking agents (RAMBAs) such as DX308 may address these shortcomings. Objectives: Characterize the therapeutic potential of recently discovered, CYP26-selective RAMBA, DX308. Materials and Methods: Preliminary in vitro assessment of potential off-target activity, metabolic and toxicologic profiling. Studies to assess safety and efficacy of topical treatment in correcting abnormal skin morphology in rhino mice. Extensive gene expression profiling by RNA sequencing and qPCR in 3D epidermis grown with keratinocytes (KCs) from keratinization disorders and healthy controls, to investigate modulation of retinoid biopathways. Results: In vitro, DX308 does not interact with off-target nuclear receptors or CYP450s, is not genotoxic, and is stable in skin, despite vigorous hepatic metabolism. In vivo, topical DX308 induces comedolysis and epidermal thickening without apparent adverse effects. Gene expression profiling shows potent modulation of retinoid-responsive genes by DX308 in both healthy and keratinization disorder KCs. Pathway analysis suggests DX308 may inhibit inflammatory and immune responses in KCs. Conclusions: These preliminary studies suggest that DX308 is an efficacious topical therapeutic with a favourable metabolic and safety profiles. DX308 may present an improved therapeutic alternative for the treatment of keratinization disorders and other retinoid-responsive skin ailments.

Identifiers

PMID35664983
PMCPMC9060145
OpenAlexW3141662333

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.