---
title: "Two Computationally Designed PDE4 Inhibitors Proposed for Plaque Psoriasis"
id: "biorxiv-13-computationally-guided-design-of-two-novel-phosphodiesterase-4-inhibitors-for"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-13-computationally-guided-design-of-two-novel-phosphodiesterase-4-inhibitors-for"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Two Computationally Designed PDE4 Inhibitors Proposed for Plaque Psoriasis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-13-computationally-guided-design-of-two-novel-phosphodiesterase-4-inhibitors-for
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Plaque psoriasis is a chronic inflammatory skin disease with symptomatic management but no cure; investigators framed the project as drug-design focused. - The study team used computational approaches to design two novel **phosphodiesterase-4** inhibitors intended to treat **plaque psoriasis**. - Authors reported that computed ADMET properties for the two candidates compared favorably to **Roflumilast**, an existing PDE4 inhibitor. - A homology analysis was performed to identify an appropriate model organism for preclinical evaluation of the candidates. - The preprint does not report in vivo efficacy data, clinical dosing, or safety outcomes from animal or human studies. - The article is a bioRxiv preprint and has not been peer reviewed; investigators declared no competing interests. - Funding sources cited include the National Science Foundation, BioMADE, and the University of California, Davis. - Next steps implied by the work include experimental validation in the chosen model organism and conventional preclinical safety and efficacy testing, but specific experimental plans were not reported in the source.
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M. James, Justin B Siegel doi: https://doi.org/10.64898/2026.10.20.760516 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Annie Liu UC Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Annie%2BLiu%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Liu%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnnie%2BLiu%2B) Emma R. M. James UC Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Emma%2BR.%2BM.%2BJames%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=James%20ER&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEmma%2BR.%2BM.%2BJames%2B) Justin B Siegel UC Davis * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Justin%2BB%2BSiegel%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Siegel%20JB&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJustin%2BB%2BSiegel%2B) * For correspondence: jbsiegel@ucdavis.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5898006/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5898006/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5898006/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.20.760516v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5898006/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Plaque psoriasis is a chronic inflammatory skin disease characterized by itchy, scaly skin. Although there is currently no cure for this disease, it can be managed with medication, such as phosphodiesterase-4 (PDE4) inhibitors. Current PDE4 inhibitors are limited and show adverse effects. With the goal to develop better PDE4 inhibitors for the treatment of plaque psoriasis, two novel drug candidates were designed with computational studies, and observed to have better ADMET properties compared to Roflumilast. A homology analysis was performed to determine the best model organism for preclinical studies of the novel candidates. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared The National Science Foundation, 2315767, 2118138, 1827246 BioMADE, FA8650-21-2-5028 University of California, Davis Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY 4.0 International license](http://creativecommons.org/licenses/by/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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