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In two identical trials of treatment for psoriasis with the topical aryl hydrocarbon receptor–modulating agent tapinarof, clearance or near-clearance of lesions occurred in a larger proportion of patients who used tapinarof cream than of those who used placebo. Side effects included folliculitis, contact dermatitis, and headache.

Background Q‐switched (QS) Nd: YAG laser is one of the treatment options for solar lentigines (SLs). However, the incidence of post‐inflammatory hyperpigmentation (PIH) is a common complication, especially in dark‐complexioned skin. Isobutylamido thiazolyl resorcinol (ITR) has been reported as a preventive modality for ultraviolet B (UVB)‐induced hyperpigmentation. Aims This study aims to evaluate the efficacy and safety of ITR for the prevention of laser‐induced PIH. Patients/Methods A randomized, evaluator‐blinded study including 24 subjects with SLs was conducted. Three SLs of each patient were randomized into three groups, which were to apply ITR twice daily, once daily, and no application for 2 weeks. Thereafter, 532‐nm QS Nd: YAG laser was performed. Incidence of laser‐induced PIH, relative melanin index (RMI), mean luminance score (L*), hyperpigmentation score, and adverse events were recorded for 2 months post‐laser. Results The incidence of PIH at the 4th week after laser treatment was significantly lower in the ITR twice‐daily group compared to the no‐application group (20.83% vs. 50%, p = 0.028). There was no statistically significant difference in RMI, mean L*, and hyperpigmentation score between treatments at all visits. No serious adverse events were reported regarding ITR application and laser treatment. Conclusion Two‐week application of ITR prior to QS: Nd YAG laser treatment may potentially reduce the incidence of PIH. A longer duration of application, including after the laser procedure, may be more beneficial for the prevention of laser‐induced PIH.

Tapinarof cream 1% is an aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration to treat atopic dermatitis (AD) in patients down to age 2 years. The aim of this study was to evaluate the safety and pharmacokinetics of tapinarof cream 1% once daily (QD) in adolescents and children with extensive AD under maximal usage conditions. Patients with a validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥ 3 and body surface area (BSA) involvement ≥ 25% (ages 12-17 years) or ≥ 35% (ages 2-11 years) were enrolled into three age cohorts (2-6, 7-11, and 12-17 years) and received tapinarof cream 1% QD for 4 weeks. Overall, 36 patients (12 per cohort) were enrolled; mean BSA affected was 42.8% (range 26.0-90.0) and mean Eczema Area and Severity Index (EASI) score was 23.8. At baseline, 28 patients (77.8%) had a vIGA-AD™ score of 3 (moderate). No-to-minimal tapinarof systemic exposure was observed (25% of post-treatment plasma samples were below the quantifiable limit of a highly sensitive assay [< 50 pg/mL]). Mean maximum plasma concentration (C ) was 2.44 ng/mL, and median time to C was 2.9 h. Eight patients (22.2%) reported treatment-emergent adverse events (TEAEs), which were mild or moderate; only one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Tapinarof was well tolerated, including on sensitive skin and extensor/flexural surfaces. Tapinarof cream exhibits highly favorable safety and pharmacokinetics in adolescents and children down to age 2 years with extensive AD. ClinicalTrials.gov: NCT05186805.

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.

Tyrosinase inhibitors are of great clinical interest as agents for the treatment of hyperpigmentary disorders; however, most compounds described in the literature lack clinical efficiency due to insufficient inhibitory activity against human tyrosinase (hTyr). Recently, we reported that thiazolyl resorcinols (4-resorcinylthiazol-2-amines and -amides) are both selective and efficacious inhibitors of hTyr in vitro and in vivo. Here, we measured dose-activity profiles of a large number of thiazolyl resorcinols and analogous compounds to better understand the molecular basis of their interaction with hTyr. We show that both the resorcinyl moiety and the thiazole ring must be intact to allow efficient inhibition of hTyr, while the substituents at the thiazole 2-amino group confer additional inhibitory activity, depending on their size and polarity. The results of molecular docking simulations were in excellent agreement with the experimental data, affording a rationale for the structural importance of either ring. We further propose that a special type of interaction between the thiazole sulfur and a conserved asparagine residue is partially responsible for the superior inhibitory activity of thiazolyl resorcinols against hTyr.

Objectives AUY922 is a novel heat shock protein inhibitor with preclinical activity in pancreatic cancer. This phase II study evaluated the efficacy of AUY922 in patients with advanced pancreatic cancer previously treated with chemotherapy. Methods In this single-arm, Simon two-stage phase II trial, patients with metastatic or locally advanced pancreatic ductal adenocarcinoma who had progressed on at least one line of chemotherapy and were of good performances status (ECOG 0 or 1) were treated with AUY922 at a dose of 70 mg/m 2 IV weekly. The primary endpoint was disease control rate (objective response and stable disease ≥16 weeks). Results Twelve patients were accrued, all of whom received treatment. At least possibly related ≥grade 3 adverse events included fatigue (8 %) and AST elevation (8 %). Ten patients were evaluable for response with 1 (10 %) having stable disease and 9 (90 %) progressive disease. The median progression-free survival was 1.6 months, and the median overall survival was 2.9 months. Conclusions AUY922 was not associated with significant efficacy in previously treated patients with advanced pancreatic cancer.

Two new very-long-chain 5-n-alkylresorcinol (AR) homologues, that is, 5-n-nonacosylbenzene-1,3-diol and 5-n-hentriacontylbenzene-1,3-diol, were isolated from acetone extracts of Ailanthus altissima samaras. These phenolic compounds were detected in nearly equal proportions, although their total content varied considerably between samples from urban-grown trees. No correlation was observed between AR levels and the physiological state of the tree, suggesting that environmental conditions may strongly influence AR biosynthesis in A. altissima. Furthermore, the isolated AR mixture exhibited antifungal activity against soil-borne phytopathogens of the genera Fusarium and Rhizoctonia.

Dichlorobenzene is beneficial to industries, however, the release of this compound into the environment causes significant damage to ecosystems and human health, as it exhibits resistance to biodegradation. Here, we show that chlorophenol and resorcinol are synthesized from 1,3-dichlorobenzene in a water ice environment (1) directly on a poly-crystalline gold surface and (2) after low-energy (<12 eV) electron irradiation of admixture films. For the latter, at energies below 5.5 eV, the electrons solely decompose the chlorinated compound into radicals that further undergo reaction with surrounding water molecules. At higher energies (i.e., >5.5 eV) additional fragments, e.g., hydroxyl radicals, produced from the dissociation of water molecules, may also be involved in the chemistry. The present results may suggest strategies for potential eco-friendly, sustainable, and scalable processes for the mitigation of these halogenated compounds such as cold plasma and radiation, in which low-energy (<10 eV) electrons are predominantly produced.

Purpose Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye. Plasma AR and their urinary metabolites may be suitable biomarkers of whole-grain (WG) wheat and rye consumption. The objective of this study was to examine plasma AR and urinary AR metabolites in response to WG wheat consumption. Methods In a randomized crossover study, 19 subjects (10 males, 9 females; BMI 22.0 kg/m 2 ; age 26 years) incorporated either 3 servings (48 g) or 6 servings (96 g) of WG wheat daily into their regular diet for 1 week. Subjects completed a 2-week washout period, abstaining from all WG consumption, before each intervention. Fasting blood and 24-h urine were collected before and after each intervention. Plasma AR homologues (C19:0, C21:0, C23:0) were quantified by GC–MS after diethyl ether and solid phase extraction and derivatization. Urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic acid] were determined using HPLC with electrochemical detection after enzymatic deconjugation and ethyl acetate extraction. Results Urinary total AR metabolites were significantly higher after 6 compared with 3 servings of WG wheat (56 vs. 32 μmol/day, P  < 0.001). This dose–response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolite concentration. Plasma total AR tended to be higher after 6 compared with 3 servings of WG wheat (103.0 vs. 86.9 nmol/L), but this difference was not significant ( P  = 0.42). Conclusion The results suggest that urinary AR metabolites from 24-h urine collections may be useful as biomarkers of compliance in intervention studies of WG wheat.

The aryl hydrocarbon receptor (AhR) has an integral role in maintaining skin homeostasis. Tapinarof cream 1% (VTAMA ® ) is an AhR agonist developed by Dermavant Sciences, an Organon Company, as a once-daily topical treatment for plaque psoriasis and atopic dermatitis (AD). It was first approved in May 2022 in the USA for the topical treatment of plaque psoriasis in adults. It was then approved in June 2024 in Japan for the topical treatment of plaque psoriasis in adults and AD in adults and pediatric patients 12 years of age and older. In December 2024, it was approved in the USA for the topical treatment of AD in adults and pediatric patients 2 years of age and older. This article summarizes the milestones in the development of tapinarof cream 1% leading to this first pediatric approval.