Zyclara (imiquimod)

Psoriasis-like models were induced in mice or keratinocytes using imiquimod (IMQ) or tumor necrosis factor-α (TNF-α)...Similar changes were detected in TNF-α-treated HaCaT cells. This suggests that α-Bisabolol may inhibit inflammation in TNF-α-treated keratinocytes and psoriasis mice through the PI3K/AKT and NF-κB pathways, providing a new theoretical basis for clinical application in the treatment of psoriasis.

Imiquimod (IMQ) was used to establish a C57 mouse psoriasis model...Western blotting revealed inhibition of the JAK1/STAT3 signaling pathway within anisole-treated psoriatic tissues. Anisole potentially reduces psoriatic-associated inflammation through the JAK1/STAT3 signaling pathway, alleviating IMQ-induced psoriasis.

In conclusion, the findings of the present study consistently demonstrated that ergothioneine had a significant ameliorative effect on the imiquimod-induced psoriasis model by modulating the NF-κB/JAK-STAT3 signalling pathway. This provides a strong experimental rationale for its potential application in psoriasis treatment.

To investigate the symptom-alleviating effects of NTZ on psoriasis and its underlying mechanisms, we used an imiquimod-induced psoriatic-like skin inflammation mouse model and IL-17-stimulated human keratinocytes. Moreover, the administration of NTZ in a mouse model of psoriasis, an IL-17-mediated skin disease, inhibited the accumulation of damaged mitochondria and suppressed Th17-mediated inflammatory responses. These findings provide preclinical evidence that NTZ may be effective in treating psoriasis and suggest that targeting the energy metabolic pathways in the skin could be beneficial for the treatment and prevention of psoriasis.

Through in vivo and in vitro experiments, this study shows that quercetin may play a therapeutic role in psoriasis and inhibit the PI3K/AKT/GLUT1 signaling pathway.

Furthermore, Birinapant positively affected oxidative stress maintenance, suggesting its potential role in promoting skin health and homeostasis. By demonstrating birinapant's efficacy, this research paves the way for further studies that could lead to the development of more effective therapies for psoriasis.

P4, N=40, Not yet recruiting, University of Michigan

P1, N=40, Completed, University of Michigan | Recruiting --> Completed | Phase classification: P4 --> P1

A rodent model of psoriasis induced by imiquimod was treated topically with these vectors, resulting in approximately a 50% reduction in TNFα levels at inflammation sites, decreased immune cell infiltration, and preservation of epidermal structure. These findings collectively underscore the potential of DIPEA-chitosan-based vectors for topical siRNA-based therapies.

P4, N=96, Recruiting, Barretos Cancer Hospital | Not yet recruiting --> Recruiting

Functional vascular normalization by IMQ increases the effectiveness of low dose of doxorubicin. To conclude, we outline IMQ repurposing as a vascular normalizing agent. Our research results may contribute to expanding the therapeutic indications for the use of IMQ in anticancer therapy in the future.

Last, we outline how blocking cis PD-L1:CD80 interactions or mutation of the intracellular domain of PD-L1, in an imiquimod-induced murine model of psoriasis, limits DC migration to the lymph node, decreases interleukin-17 production by CD4+ T cells in the lymph node, and reduces epidermal thickening. Therefore, PD-L1 and CD80 interactions are important regulators of DC migration to the draining lymph node.

P1, N=16, Completed, Medical University of South Carolina | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024

Here, we demonstrate the effectiveness of the TLR7/8 agonist imiquimod (IMQ) in treating both local tumors and distant metastases...Combining topical and systemic IMQ or IFN-I generates a CD8+ T cell-dependent response at metastatic sites, reinforced by PD-1 blockade, leading to long-lasting memory. Analysis of cohorts of patients with melanoma demonstrates DC-specific TLR7/8 upregulation by IFN-I, supporting the translational potential of combining systemic IFN-I and topical IMQ to improve immunotherapy of topically accessible tumors.

In this study, we successfully synthesized mesoporous polydopamine (MPDA) with photothermal effects for the co-delivery of the chemotherapeutic drug doxorubicin (DOX) and the immune adjuvant imiquimod (R837), resulting in the development of a multifunctional nanoplatforms termed MDR. Intratumoral injection in breast cancer-bearing mice further demonstrated that the MDR + NIR group significantly inhibited tumor growth compared to other groups, with no apparent side effects. In conclusion, the multifunctional nanoplatforms integrating photothermal therapy, chemotherapy, and immunotherapy are expected to provide a novel therapeutic approach for the multimodal treatment of breast cancer.

P2, N=20, Recruiting, Melanoma Institute Australia | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

Diphenciprone, imiquimod and 5-florouracil were included as topical treatments and bacillus Calmette-Guerin, interleukin 2, rose bengal, talimogene laherparepvec and electrochemotherapy were included as intralesional treatments. Brief comments on other alternatives in development such as interferon-alpha, interleukin-12, ipilimumab and intralesional daromun are presented...It has also been described in a few papers that non-injected lesions may respond after the application of a local therapy in distant skin-metastases. Many of these intralesional treatments are being combined in different investigations with systemic immunotherapies, with the aim of obtaining synergic responses in those patients with refractory disease.

The formulation was prepared by loading a photosensitiser (IR780) and an immunotherapeutic drug (imiquimod; IMQ) into temperature- and pH-responsive chitosan-based NPs functionalized with tumor-targeting aptamers...Moreover, IMQ promotes the maturation of dendritic cells (DCs), which then activate cytotoxic T-lymphocytes (CTLs); these T-cells go on to provide immunotherapy of metastatic tumor cells. The metastatic tumor cells can be induced to undergo ferroptosis by the addition of arachidonic acid (AA), which interacts with interferon cytokines (IFN-γ) released from CTLs.

Our results highlight the importance of specific genes and pathways, particularly those associated with IFN-γ pathway and IL-6/JAK-STAT signaling. AI/ML predictions indicate potential associations with various diseases and provide valuable insights for the development of novel therapeutic approaches for psoriasis and related disorders.

P3, N=1630, Not yet recruiting, VA Office of Research and Development | Trial completion date: Jan 2031 --> Jun 2032 | Trial primary completion date: Jan 2030 --> Jun 2031

In this study, we successfully synthesized mesoporous polydopamine (MPDA) with photothermal effects for the co-delivery of the chemotherapeutic drug doxorubicin (DOX) and the immune adjuvant imiquimod (R837), resulting in the development of a multifunctional nanoplatforms termed MDR. Intratumoral injection in breast cancer-bearing mice further demonstrated that the MDR + NIR group significantly inhibited tumor growth compared to other groups, with no apparent side effects. In conclusion, the multifunctional nanoplatforms integrating photothermal therapy, chemotherapy, and immunotherapy are expected to provide a novel therapeutic approach for the multimodal treatment of breast cancer.

It was also confirmed that SIRT6 and Ki67 expression was consistently upregulated inpsoriatic lesional skin,mouse models of psoriasis established by imiquimod treatment, and HaCat cells treated with M5...In conclusion, the knockdown of the SIRT6 promoted the nuclear translocation of FOXO1 by upregulating its acetylation level, thereby inhibiting M5-induced hyperproliferation and inflammation of keratinocyte. Given the crucial role of SIRT6 in psoriasis, it may represent a promising target for the development of small-molecule inhibitors with therapeutic potential for psoriasis.

In addition, TAVO101 showed strong efficacy in both TSLP/OVA-induced asthma and imiquimod induced psoriasis models in hTSLP/hTSLPR double knock-in mice. We further conducted Fc engineering to optimize TAVO101 antibody with reduced affinity to Fcγ receptors and C1q protein but with increased affinity to FcRn receptor for half-life extension. By recognizing a different epitope, similarly potent neutralization of TSLP activities, and longer circulating half-life than tezepelumab, novel anti-TSLP antibody TAVO101 offers a potential best-in class therapeutics for various TSLP-mediated diseases.

P3, N=153, Recruiting, AiCuris Anti-infective Cures AG | Trial completion date: Apr 2025 --> Nov 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

In the pathological condition of psoriasis, systemic IL-17A elevation can trigger microglia activation, provoke pro-inflammation mediators to release, evoke neuroinflammation, subsequently inhibit hippocampal neurogenesis, and result in depression. IL-17A, as an important pathogenic factor in psoriasis, contributes to its critical role in mediating systemic inflammation and depression comorbidity.

CT26 mouse model was established to assess the synergistic effect of silencing HIF-1α combined with oxaliplatin (OXA) and imiquimod (IMQ) on tumor growth. Compared with those in the control group, the expression levels of the anti-inflammatory cytokines IL-10 and IL-4 significantly decreased (P < 0.05). In conclusion, our findings suggest that inhibiting HIF-1α could serve as a rational strategy to enhance the antitumor response in the TME.

The study concluded the immunotherapeutic activity of ATSLA in experimental psoriatic skin lesions. This will enrich the psoriasis immunotherapeutic list with novel candidates of parasitic origin.

Imiquimod (IMQ)-induced psoriasis-like mice were used to verify the therapeutic effects of SCP...Besides, SCP could also inhibit the phosphorylation of PI3K, Akt, and mTOR, and the good docking activity of SCP with the three pathway proteins further proved SCP can treat psoriasis via PI3K/Akt/mTOR signaling pathway. In conclusion, SCP may be a potential drug for treating psoriasis and is worth further research.

The SNAs@CCMR consisted of antisense oligonucleotides grafted gold nanoparticles (SNAs) as core and TLR7 agonist imiquimod (R837) functionalized cancer cell membrane (CCM) as shell, in which the acid-labile Schiff base bond was used to connect the R837 and CCM...These chain processes not only damaged the primary tumor, but also produced plenty of tumor-associated antigens, which matured the surrounding dendritic cells (DCs) and activated anti-tumor T cells along with the released R837, resulting in the enhanced immunotherapy with suppressive immune escape. Both in vivo and in vitro experiments demonstrated that our nanoparticles were able to inhibit primary tumor and its metastasis via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immune activations, which provided a promising strategy to reprogram the immunosuppressive microenvironment in tumor tissue for better malignant tumor therapy.

Inhibiting GBP5 can mitigate the renal injury caused by psoriasis through NF-κB/STAT3 axix.

In summary, Gyp reduced excessive cell growth and inflammation in psoriasis by suppressing nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) through activation of Nrf2.

P2, N=85, Recruiting, Baylor College of Medicine

P1, N=15, Active, not recruiting, Medical University of South Carolina | Trial completion date: Sep 2024 --> Dec 2024

P=N/A, N=6, Terminated, University of California, Davis | N=110 --> 6 | Active, not recruiting --> Terminated; PI failed to submit the study for continuing review to IRB, failed to respond.

Nrf2 and GPX4 might be the two major targets of SHK in psoriatic skin lesion. Our study highly lighted the basic biological mechanism of SHK on ferroptosis regulation.

This work suggests that the highly lipophilic prodrug approach can efficiently deliver IMQ to intestinal lymphatics. In addition, this study demonstrates the feasibility of an amide prodrug approach for intestinal lymphatic targeting.

Oral propranolol is a mainstay of treatment for IH and is well-tolerated, though propranolol-refractory IH and other drug-related adverse events are documented and can limit its usage. From this preliminary analysis, we discerned that hemangioma tissues can be grown in tissue culture and used for drug treatment studies. We also conclude acute and chronic modulation of cell cycle, angiogenesis factors, and immunostimulatory conditions may be associated with imiquimod mechanisms of action in hemangioma involution.

BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.

Here, in this study, we investigated the detrimental impact of an 8-week chronic unpredictable stress (CUS) protocol on the progression of arthritis and psoriasis using collagen-induced arthritis (CIA) and imiquimod (IMQ)-induced psoriasis rat models, respectively. Moreover, the therapeutic efficacy of MTX was notably reduced in stressed rats compared to non-stressed, underscoring the detrimental effects of chronic stress on treatment outcomes. Taken together, our results emphasize the importance of considering chronic stress as a critical factor in the management of autoimmune diseases.

A mouse model for psoriasis combined with SDs was established by smearing 62.5 mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300 mg/kg at days 6-7...XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-RORα axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-α production to suppress IL-23/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis.

Local therapies can be considered in superficial and low-risk nodular BCCs, with imiquimod frequently used for its antitumor and immunoregulatory properties...Interferons and Interleukin-2 were evaluated in a small number of studies with different results. Systemic immunotherapies with programmed death-ligand 1 (PD-L1) inhibitors showed inconsistent results in patients with advanced BCCs, being effective in some patients that progressed on or were intolerant to hedgehog pathway inhibitors (HHI).

In the imiquimod (IMQ) -induced mouse inflammatory model, the therapeutic effect of GFRS on the pathogenesis of psoriasis-like dermatitis was studied...GFRS restored IMQ-induced spleen size and reduced the secretion and expression of TNF-α, IL-6, Interferon-γ (IFN-γ) and IL-17 A in serum. In summary, our results demonstrate that GFRS alleviates IMQ-induced dermatitis symptoms, effectively reduces the secretion of inflammatory factors, and inhibits IL-17 A expression.