Dovonex (calcipotriol)
/ LEO Pharma, Novartis
- LARVOL DELTA
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April 26, 2025
Regulation of T cell polarization using HIF1a stabilizer Roxadustat in MC903 induced Atopic Dermatitis
(IMMUNOLOGY 2025)
- "AD associated genes, MMP12, TSLP, GATA3 and CD14 were observed to be decreased in Roxadustat treated mice (n=5/group p=<0.05). Overall, topical treatment of AD with HIF1a stabilizer, Roxadustat in mice is associated with a decrease in the progression of AD."
Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Respiratory Diseases • CD14 • GATA3 • HIF1A • IL13 • IL4 • TSLP
April 26, 2025
Efficacy Evaluation of Novel Therapeutics Targeting TSLP or TSLPRDrug Candidates Using TSLP/TSLPR Double Humanized Mouse Model on BALB/c Background
(IMMUNOLOGY 2025)
- "Tezepelumab, an approved monoclonal antibody against TSLP, as well as other therapeutic antibodies that target TSLP, significantly alleviated the phenotypes induced by MC903. In addition, in both the OVA- and HDM-induced asthma models, we found anti-TSLP antibody significantly reduced the infiltration of eosinophils and other lymphocytes in the lung."
Preclinical • Asthma • Dermatitis • Dermatology • Immunology • Respiratory Diseases • CRLF2 • IL2 • TSLP
April 26, 2025
The effect of parental T-cell deficiency on offspring response to skin inflammation
(IMMUNOLOGY 2025)
- "To assess the role of parental T cell deficiency in skin immune response, we employed a mouse model of atopic dermatitis induced by topical application of the Vitamin D3 analog, MC903...Furthermore, the phenotype persisted even in the F2 generation, independent of their genotype. These data suggest that T cell deficiency in either parent, can non-genetically influence the offspring skin immune response."
Late-breaking abstract • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation
April 26, 2025
BGB-45035, a highly potent IRAK4 degrader with differentiated MOA, demonstrates strong and sustained anti-inflammatory effects in murine models of autoimmune diseases
(IMMUNOLOGY 2025)
- "We have developed BGB-45035, a highly selective and potent IRAK4 degrader to completely inhibit IRAK4 function, which demonstrated superior performance compared to KT-474 ( Kymera/Sanofi ). Additionally, in a therapeutic mouse model of MC903-induced atopic dermatitis, BGB-45035 achieved deeper IRAK4 degradation in both tissue and peripheral compartments, along with improved efficacy and reduced inflammatory biomarkers. These data highlight the best-in-class potential of BGB-45035 to effectively block various immune cell functions and induce long-lasting effects to treat inflammatory and autoimmune diseases."
Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL1R1 • IL33 • IRAK4
April 16, 2025
Interleukin-13-mediated alterations in esophageal epithelial mitochondria contribute to tissue remodeling in eosinophilic esophagitis.
(PubMed, bioRxiv)
- "Mitochondria were evaluated in human biopsies, MC903/Ovalbumin-induced murine EoE, and human esophageal keratinocytes. Esophageal keratinocytes were treated with EoE-relevant cytokines and JAK/STAT inhibitor ruxolitinib...These findings further lay a foundation for exploration of level of esophageal epithelial mitochondria as a predictive biomarker for response to dupilumab. IL-13 promotes mitochondrial biogenesis in esophageal epithelium, contributing to impaired squamous cell differentiation."
Journal • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • IL13 • IL4 • TFAM
March 26, 2025
Therapeutic Potential of LCAA-PSF in Atopic Dermatitis: Insights from an MC903-Induced Mouse Model
(EAACI 2025)
- No abstract available
Preclinical • Atopic Dermatitis • Dermatitis • Immunology
April 14, 2025
A tri-compound formula comprising Ginsenoside Rg1, tetrandrine and icariin alleviates atopic dermatitis symptoms in a mouse model.
(PubMed, Phytomedicine)
- "This study, for the first time, demonstrated that the topical application of GTI alleviates symptoms of AD without overt toxicity in a calcipotriol-induced AD mouse model. The anti-AD effects of GTI are associated with the suppression of allergic reactions, reduction of hyperactive immune responses, improvement of skin barrier function, and inhibition of MAPK activation. These findings suggest that GTI has the potential to be developed into a safe and effective treatment for AD."
Journal • Preclinical • Allergic Rhinitis • Allergy • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • CD4 • CLDN1 • IL1B • IL4 • TJP1
March 31, 2025
Topical administration of coumarin derivatives alleviates skin inflammatory symptoms in atopic dermatitis model.
(PubMed, Biomed Pharmacother)
- "Experiments on an MC903-induced mouse model of AD revealed that topical administration of C#6 for 10 days led to a significant reduction in ear and epidermal thickness...Additionally, co-culture experiments revealed that C#6 treatment of TNF-α and IFN-γ-stimulated HaCaT cells suppressed inflammatory cytokines expression by THP-1 cells. Collectively, these findings demonstrate that C#6 exerts its anti-atopic effects by suppressing Th2-driven inflammation, reducing eosinophilic infiltration, modulating immune-epidermal crosstalk, and maintaining skin microbiome homeostasis, highlighting its potential as a promising therapeutic agent for AD management."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IFNG • PTPRC • TLR2 • TLR3 • TNFA • TSLP
March 22, 2025
Ultraviolet-treated riboflavin alleviates atopic dermatitis by inhibiting NLRP3 inflammasome activation and M1 macrophage polarization via histone lactylation.
(PubMed, Biochem Pharmacol)
- "Using a MC903-induced mouse model, we demonstrate that topical UV-treated riboflavin significantly attenuates AD progression...NLRP3 activation in vivo partially reverses these effects, confirming the central role of NLRP3 inflammasome inhibition. Our findings reveal a novel epigenetic mechanism of UV-treated riboflavin in modulating immune responses in AD, highlighting its potential as a therapeutic strategy for inflammatory skin disorders."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IL1B • NLRC5 • NLRP3 • TSLP
March 10, 2025
Triclosan exacerbates atopic dermatitis in mouse models via thymic stromal lymphopoietin.
(PubMed, J Dermatol Sci)
- "Topical and systemic administration of triclosan exacerbates AD-like skin inflammation in murine models, with TSLP being a central mediator of this process. The translational relevance of these findings to human disease remains uncertain, as no direct human data are available."
Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • CRLF2 • TSLP
February 26, 2025
The Use of a Novel Tri-Modal Therapeutic to Resolve Pruritus and Inflammation in Murine Models of Atopic Dermatitis
(AAD 2025)
- "Using established models, MC903 (calcipotriol) was applied to murine ears to induce 1) inflammatory-predominant AD(4), and 2) itch-predominant AD(5,6)...In an itch-predominant model of AD, topical NOA-104 rapidly resolved scratching time and occurrence within 3 days of initiating treatment, and a significant reduction in pruritic biomarker CXCL1, while increasing the genetic expression of barrier function protein, filaggrin. Discussion These studies demonstrate potential for translation of NOA-104 into human studies; further work to follow."
Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Inflammation • Pruritus • CXCL1 • FLG • IL13 • IL4 • STAT6
February 19, 2025
Role of Siglec-E in MC903-Induced Atopic Dermatitis.
(PubMed, Exp Dermatol)
- "We finally revealed that Siglec-E was expressed on eosinophils and reduced the eosinophils infiltration to the MC903-treated ear skin with the suppression of CD49d, a necessary integrin for eosinophil migration to skin tissue [1], expression on eosinophils. These findings elucidated the inhibitory role of Siglec-E in MC903-induced AD."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • CD4 • IL33 • ITGA4 • TNFSF4
February 11, 2025
Regulation of T cell polarization using HIF1a stabilizer, Roxadustat in MC903 induced Atopic Dermatitis
(AAAAI-WAO 2025)
- "AD associated genes, MMP12, TSLP, GATA3 and CD14 were observed to be decreased in Roxadustat treated mice (n=5/group p=<0.05). Conclusions Topical treatment of AD with HIF1a stabilizer, Roxadustat in mice is associated with a decrease in the progression of AD."
Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Respiratory Diseases • CD14 • GATA3 • HIF1A • IL13 • IL4 • TSLP
February 11, 2025
Briquilimab, an Anti-Human CD117 Antibody, Treats Low-Calcemic Vitamin D3 Analog MC903-Induced Dermatitis in Mouse Model Expressing Chimeric Human/Mouse CD117
(AAAAI-WAO 2025)
- "Therapeutic briquilimab significantly improved skin condition (clinical score 3.0±0.7 vs. placebo 7.5±0.5, P<0.05), with significant decreases in dermal MC count (0.5±0.1x10 2 /mm 2 vs. placebo 2.6±0.3x10 2 /mm 2 , P<0.05) and leukocyte recruitment (1.0±0.2x10 2 /mm 2 vs. placebo 6.2±0.4x10 2 /mm 2 , P<0.05). Conclusions This study provides early evidence that briquilimab may be a novel therapeutic agent for conditions associated with induction of TSLP and that are independent of specific allergen sensitization."
Preclinical • Dermatitis • Dermatology • Immunology • KIT • TSLP
January 31, 2025
NLRX1 deficiency exacerbates skin inflammation in atopic dermatitis by disrupting mitophagy.
(PubMed, Clin Immunol)
- "We observed a significant decrease in NLRX1 expression in AD skin lesions and MC903-indued AD dermatitis...Furthermore, topical application of NLRX1 agonist alleviated AD progression, including reduced ear thickness, diminished redness, and improved skin barrier function. This study provides novel insights into the regulatory role of NLRX1 in skin inflammation in AD, highlighting the potential therapeutic implications of targeting NLRX1 and mitophagy in AD treatment."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • TSLP
January 29, 2025
N-Heterocyclic functionalized chalcone derivatives as anti-inflammatory agents for atopic dermatitis treatment by inhibiting JAK1/STAT3 signaling pathway.
(PubMed, Bioorg Chem)
- "In vivo studies revealed that 4f could improve the skin condition of AD-like mice, reduce inflammatory infiltration, inhibit the expressions of p-JAK1/JAK1 and p-STAT3/STAT3, and mitigate the excessive immune response on MC903-induced AD-like mice. The molecular docking study indicated that 4f had an obvious binding site with the target 4ehz and 6QHD. Therefore, these derivatives may be considered as potent agents for AD treatment by inhibiting JAK1/STAT3 signaling pathway."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • JAK1
January 28, 2025
Optimized nanostructured lipid carriers from aceh traditional coconut (Pliek) oil: a promising topical formulations for atopic dermatitis.
(PubMed, Arch Dermatol Res)
- "Histological analysis demonstrated that the NLC-PL gel (2.5% w/w pliek oil) significantly reduced MC903-induced ear thickness and inflammation compared to the negative control (p 0.05). Enzyme-Linked Immunosorbent Assay (ELISA) confirmed its role as a c-jun N-terminal kinase 1 (JNK1) inhibitor, supporting its potential as targeted topical therapy for AD. This study aligns with the study's objective to develop innovative treatments for AD."
Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • MAPK8
December 31, 2024
BLOC1S1 Control of Vacuolar Organelle Fidelity Modulates Murine TH2 Cell Immunity and Allergy Susceptibility.
(PubMed, Allergy)
- "BLOC1S1 depletion in mouse CD4+ T cells mediated disruption of mitochondrial integrity to initiate a predominant TH2-responsive phenotype via STING-NF-κB-driven signaling of the canonical TH2 regulatory program."
Journal • Preclinical • Allergy • Asthma • Dermatitis • Dermatology • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CD4 • GATA3 • IL13 • IL4 • IL5 • STAT6 • STING
December 27, 2024
Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.
(PubMed, J Allergy Clin Immunol)
- "Our study demonstrates that loss of epithelial IKKβ signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. The IkkβEEC-KO/EoE mouse model closely mirrors human EoE, providing a valuable tool for investigating disease mechanisms and therapeutic targets. This model can facilitate the development of strategies to prevent chronic inflammation and tissue remodeling in EoE."
Journal • Preclinical • Allergy • Eosinophilic Esophagitis • Fibrosis • Food Hypersensitivity • Gastrointestinal Disorder • Immunology • Inflammation • RELA
December 26, 2024
Long-term application of MC903 in mice prolongs the characteristic symptoms of atopic dermatitis, such as inflammation, skin barrier dysfunction, and itching.
(PubMed, Exp Anim)
- "All these changes were observed within two weeks after the initial application of MC903 and thereafter persisted throughout the experimental period. In conclusion, our data indicate that the long-term application of MC903 prolongs the duration of the three major symptoms of AD."
Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus • IL13 • IL33 • IL4 • TSLP
December 17, 2024
Dictamnus dasycarpus Turcz. Root Bark Improves Skin Barrier Function and Symptoms of Atopic Dermatitis in Mice.
(PubMed, Int J Mol Sci)
- "This study was designed to investigate the inflammatory and skin barrier protective effects of D. dasycarpus in mice with calcipotriol (MC903)-induced atopic dermatitis (AD)...In RAW264.7 cells, EEDD reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) expression and suppressed the phosphorylations of extracellular signal-regulated kinase (ERK) and p38. These results suggest that the root bark of D. dasycarpus has therapeutic potential due to its anti-dermatitis and skin barrier protective effects in AD and that it could be used as an ingredient in skincare products."
Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Oncology • Pruritus • CXCL8 • IL4 • TNFA • TSLP
December 12, 2024
Differential regulation of pruritic sensation and emotion by cannabinoid type 1 receptors on mPFC glutamatergic and GABAergic neurons.
(PubMed, Acta Pharmacol Sin)
- "Chloroquinoline (CQ)-induced acute and calcipotriol (MC903)-induced chronic itch models were established...CB1Rs on GABAergic, but not glutamatergic, neurons regulated acute itch-induced aversion. These results may guide the development of therapeutic strategies targeting CB1Rs to treat itch-induced sensory and emotional responses."
Journal • Dermatology • Mood Disorders • Pruritus • Psychiatry
November 24, 2024
Melatonin treatment increases skin microbiota-derived propionic acid to alleviate atopic dermatitis.
(PubMed, J Allergy Clin Immunol)
- "Our study demonstrates that melatonin alleviates AD through skin microbiota/propionic acid/GPR43/FABP5 axis, highlighting a novel role of melatonin as a modulator of skin microbiota to alleviate AD."
Journal • Atopic Dermatitis • CNS Disorders • Dermatitis • Dermatology • Immunology • Sleep Disorder • Transplantation • FABP5
October 21, 2024
Oral Administration of Taurodeoxycholate, A GPCR19 Agonist, Effectively Ameliorates Atopic Dermatitis in A Mouse Model.
(PubMed, Exp Dermatol)
- "In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models...TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1β, tumour necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients."
Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Pruritus • IL13 • IL1B • IL33 • TNFA • TSLP
August 06, 2024
Potent and selective oral STAT6 degrader, KT-621, inhibits IL-4 and IL-13 functions in human cells and blocks TH2 inflammation in vivo
(EADV 2024)
- "We also compared the efficacy of KT-621 to dupilumab in vivo in an MC903 induced atopic dermatitis model and a HDM induced asthma model in the IL4/IL4RA humanized mice. STAT6 degradation is a potential novel oral approach for blocking the IL-4/IL-13 pathways. These data demonstrate the potential of KT-621 for the treatment of atopic dermatitis and other allergic diseases with best- in-pathway potential given its biologics-like activity profile and oral bioavailability. KT-621 is expected to be in a human Phase 1 trial in the second half of 2024."
Preclinical • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Inflammation • Respiratory Diseases • Targeted Protein Degradation • IL13 • IL4 • IL4R • STAT6
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