Related Experiment Video
Updated: Jun 27, 2026
The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis
Published on: July 11, 2013
Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of
E Pavez Loriè1, M Cools, M Borgers
1Department of Medical Sciences/Dermatology, Uppsala University, SE-751 85 Uppsala, Sweden.
Background:
An alternative approach to retinoid therapy is to inhibit the cytochrome P450 (CYP)-mediated catabolism of endogenous all-trans retinoic acid in the skin by applying retinoic acid metabolism blocking agents such as talarozole (R115866).
Objectives:
To study the effects of topical talarozole on retinoid biomarkers in normal skin in a randomized phase I trial.
Methods:
Gels containing talarozole (0.35% or 0.07%) and vehicle were applied once daily for 9 days on either buttock of 16 healthy volunteers. Epidermal shave biopsies (for mRNA analysis) and punch biopsies (for histology and immunofluorescence analysis) were collected from the treatment areas. Genes encoding the following were studied by quantitative real-time polymerase chain reaction: cellular retinoic acid binding protein 2 (CRABP2), cytokeratins (KRT2 and KRT4), CYP26A1, CYP26B1, CYP26C1 and CYP2S1, two enzymes in the retinol metabolism (retinal dehydrogenase-2 and retinol acyltransferase) and two proinflammatory cytokines [interleukin (IL)-1alpha and tumour necrosis factor-alpha].
Results:
Talarozole treatment increased the mRNA expression of CRABP2, KRT4, CYP26A1 and CYP26B1 dose dependently, and decreased the expression of KRT2 and IL-1alpha compared with vehicle-treated skin. No mRNA change in retinol-metabolizing enzymes was obtained. There was no induction of epidermal thickness or overt skin inflammation in talarozole-treated skin. Immunofluorescence analysis confirmed an upregulation of KRT4 protein, but no upregulation of CYP26A1 and CYP26B1 expression was detected.
Conclusions:
Talarozole influences the biomarker pattern consistently with increased retinoic acid stimulation. The low irritancy of talarozole at the two examined dosages is a possible advantage over topical retinoids.
Insights
Talarozole, a retinoic acid metabolism blocking agent, increased key retinoid biomarkers in normal skin. This topical treatment showed low irritancy, suggesting a potential advantage over traditional retinoids for skin therapy.
Area of Science:
- Dermatology
- Pharmacology
- Molecular Biology
Background:
- Retinoid therapy is crucial for skin conditions.
- Cytochrome P450 (CYP)-mediated catabolism reduces endogenous retinoic acid levels.
- Retinoic acid metabolism blocking agents, like talarozole, offer an alternative by inhibiting this breakdown.
Purpose of the Study:
- To evaluate the effects of topical talarozole on retinoid biomarkers in normal skin.
- To assess the safety and tolerability of talarozole in a Phase I clinical trial.
Main Methods:
- A randomized, double-blind, vehicle-controlled Phase I trial was conducted.
- Healthy volunteers received daily topical application of talarozole (0.07% or 0.35%) or vehicle for 9 days.
- Gene expression (mRNA) and protein levels of retinoid biomarkers, cytokeratins, and inflammatory cytokines were analyzed from skin biopsies.
Main Results:
- Talarozole treatment dose-dependently increased mRNA expression of CRABP2, KRT4, CYP26A1, and CYP26B1.
- Expression of KRT2 and IL-1alpha was decreased, while retinol metabolism enzymes remained unchanged.
- No significant increase in epidermal thickness or overt skin inflammation was observed; KRT4 protein was upregulated, but CYP26A1/B1 protein levels were not detected.
Conclusions:
- Talarozole effectively modulates retinoid biomarkers, indicating increased retinoic acid activity in the skin.
- The observed low irritancy of talarozole at tested concentrations presents a potential advantage compared to conventional topical retinoids.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:27Acne Infection
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...