Zyclara (imiquimod)

P1, N=300, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=117 --> 300

Imiquimod enhances CD47 targeting in phagocytosing and removing OSCC cells by activating macrophage TLR7-NF-κB activation and subsequent M1 polarization, providing a promising approach for treating OSCC.

P1/2, N=18, Not yet recruiting, Amsterdam UMC Stichting

In mice, USP22 deficiency alleviates imiquimod (IMQ)-induced psoriasis-like dermatitis with reduced inflammatory cell infiltration and splenomegaly. In an acute liver injury model, USP22 deficiency reduces TNF/D-gal-induced inflammatory cytokine expression, liver damage, and inflammatory death, whereas MARCH2 deficiency increases TNF/D-gal-induced inflammatory cytokine expression and exacerbates pathological features of acute liver injury. These findings demonstrate that MARCH2 and USP22 reciprocally regulate K27-linked polyubiquitination and stability of TNF-R1, revealing regulatory mechanisms on TNF-R1-mediated inflammatory response.

A murine psoriasis model was induced by 6-day continuous topical imiquimod (IMQ) application; cellular models were established by stimulating keratinocyte lines with tumor necrosis factor-alpha (TNF-α)/interleukin-17A (IL-17A)...siNrf2 abolished Nef-mediated inhibition of NF-κB/ERK phosphorylation, cytokine down-regulation and ΔΨm loss. Neferine ameliorates psoriasis by inducing oxidative stress-driven apoptosis in hyper-proliferative keratinocytes and by activating Keap1-Nrf2-mediated anti-inflammatory signaling to block the IL-23/IL-17 axis, offering a promising small-molecule strategy for psoriasis management.

Therefore, this work aimed to evaluate the potential effect of enzymatically-modified isoquercitrin (EMIQ, 50 and 100 mg/kg body weight "b.wt", administered orally for 8 days), in comparison with methotrexate (MTX, a synthetic drug), against imiquimod (IMQ)-induced psoriatic lesions in female BALB/c mice. Moreover, oral administration of EMIQ prevented significantly (P < 0.001) the vascular permeability associated with augmented Evans blue leakage and dermal accumulation of degranulated mast cells, suggesting a reduction in inflammation and edema. Taken together, our study demonstrated that EMIQ can alleviate psoriasis and may be considered as a promising strategy for psoriasis treatment via targeting IL-23/IL-17A axis and mast cell degranulation.

In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways.

Using cellular and imiquimod-induced mouse models, we assessed PTPN2 expression and function using multiple techniques, including immunofluorescence, co-immunoprecipitation, and Western blotting...PTPN2 overexpression attenuated psoriatic pathology, and this therapeutic benefit was further enhanced by co-administering the autophagy inducer rapamycin. Collectively, our results delineate a novel mechanism by which PTPN2 alleviates psoriasis-like pathology in keratinocytes by targeting the STING-STAT3 pathway and promoting autophagy and apoptosis. These findings indicate that PTPN2 is a potential therapeutic target, with in vivo validation supporting its translational relevance.

In vivo, RNF213 depletion attenuated inflammation in an NF-κB-dependent imiquimod-induced ear swelling model...Collectively, these findings establish RNF213 as a pivotal regulator of NF-κB-driven inflammation and suggest that the p.R4810K variant amplifies inflammatory signaling, thereby contributing to MMD pathogenesis. This study not only advances our understanding of MMD pathophysiology but also highlights potential therapeutic strategies targeting inflammation.

We combined in vivo and in vitro approaches to examine SIK2's role in an imiquimod (IMQ)-induced psoriasis model and activated neutrophils...In vitro, SIK2 overexpression resulted in reduced cell viability and proliferation, with corresponding reductions in IL-1β, IL-17, IL-23, and Matrix Metallopeptidase 9 levels, whereas overexpression of CXCL5 reversed these effects. Our findings suggest that SIK2 acts as a critical modulator in psoriasis by influencing CXCL5-mediated IL-23 secretion in neutrophils, underscoring the potential of SIK2 as a therapeutic target to alleviate the inflammatory responses in psoriasis.

EA alleviates psoriasiform dermatitis by restoring keratinocyte homeostasis, suppressing immune cell infiltration and NET formation, suggesting its potential as a therapeutic agent derived from TCM.

The combination of IMQ with HDR brachytherapy induces a synergistic effect, improving the therapeutic antitumor effect of brachytherapy. Our data indicate that it is reasonable to use drugs that prevent changes in the TME in combination with radiotherapy.