Inhibition of lysosomal cholesterol release by ITZ reprogrammed M2 macrophages into an M1-like phenotype, revealing a novel mechanism that may serve as a foundation for developing innovative TAM-targeted immunotherapies.

P=N/A, N=36, Not yet recruiting, Cairo University

P=N/A, N=52, Active, not recruiting, Cairo University

Management required tailored antifungal regimens (amphotericin B, fluconazole, flucytosine) and careful therapeutic drug monitoring to address immunosuppressant interactions...Within this complex clinical scenario, early recognition, multidisciplinary care, and individualized treatment strategies are paramount. They underscore the need for heightened clinical vigilance and further research to optimize outcomes in this vulnerable patient population.

Azole antifungal agents, such as fluconazole (FLC), have been widely used as first-line treatments owing to their broad-spectrum efficacy and relatively favorable safety profiles...Most critically, in vitro CYP inhibition assays revealed that T24 did not significantly inhibit five major CYP isoforms, including CYP3A4, which is primarily responsible for azole-related drug interactions. These findings suggest that T24 represents a promising candidate for the development of next-generation antifungal agents with improved therapeutic indices and reduced risk of drug interactions.

Rarely, this condition is related to a suppressor of fused gene mutation, which occurs downstream from Smoothened, and is unresponsive to Smoothened inhibitors including vismodegib and sonidegib. Genetic testing was negative for patched 1 and patched 2 mutations but positive for a heterozygous suppressor of fused mutation. Patients with basal cell nevus syndrome should be treated with surgical excision, counseled on sun protection, screened and monitored for complications, and treated with vismodegib (if associated with patched 1 mutation) or itraconazole (if associated with suppressor of fused mutation).

P=N/A, N=60, Completed, The Second Affiliated Hospital of Hunan University of Chinese Medicine; The Second Affiliated Hospital of Hunan University of Chinese Medicine

P4, N=210, Completed, Obstetrics and Gynecology Hospital Affiliated to Fudan University; Obstetrics and Gynecology Hospital Affiliated to Fudan University

The PK of mocravimod and mocravimod-phosphate were bioequivalent with or without co-administration of multiple doses of itraconazole and a moderate interaction is observed when co-administered with cyclosporin. The most commonly-reported treatment-emergent adverse events were bradycardia and decreased lymphocyte count, which are expected side effects for S1PR modulators.

P1, N=14, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

P1, N=14, Not yet recruiting, Boehringer Ingelheim

PXR inhibition with okadaic acid or ketoconazole (KTZ) partially restored interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-12, interferon (IFN)-γ, and IFN-α levels and blocked the DENV2 infection-induced expression of Srebp2, Pparγ, Cd36, and Sqle...Thus, the present investigation led to the characterization of the PXR-dependent reprogramming of fatty-acid and cholesterol metabolism and immune suppression promoted by DENV2 to facilitate its replication. Taken together, our data position PXR as a new druggable target for dengue treatment.