Tumor-derived PGRN is associated with immunosuppressive macrophage features in OSCC, at least in part through a SORT1-linked cholesterol efflux program involving downstream PPARγ-LXRα activation. These findings support a role for the PGRN-SORT1-associated axis as a potential immunometabolic pathway associated with macrophage cholesterol efflux and phenotypic features in OSCC.

Furthermore, this analysis synthesizes recent molecular insights connecting fibrosis and inflammation via target engagement biomarkers (e.g., FABP4, CD36) and proposes actionable, biomarker-driven trial designs, including adaptive basket trials, to bridge current gaps in dermatology-specific translation. Demonstrating localized anti-fibrotic and anti-inflammatory efficacy with minimal systemic risk could establish pioglitazone as a mechanism-based, disease-modifying therapy for a broad spectrum of fibrotic and scarring dermatologic disorders.

P2, N=300, Recruiting, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting

The constructed prognostic model and the identified potential therapeutic targets provide new strategies to address immune therapy resistance for CRC.

We also found that PPARγ activators, ciglitazone and pioglitazone, significantly inhibited the TGF-α-induced migration of HuH7 cells. Cilostazol and dipyridamole also inhibited the activation of AKT but not EGFR. Taken together, these results strongly suggest that cilostazol and dipyridamole inhibit TGF-α-induced HCC cell migration by suppressing the AKT pathway through PPARγ activation.

Molecular docking using PyRx, followed by refined docking with the Schrödinger Glide XP module and binding free energy analysis using Schrödinger Prime MM-GBSA, identified oleic acid (PubChem ID: 445639) as the most promising compound, with a docking score of -9.451 kcal/mol and binding free energy (ΔGbind) of -108.21 kcal/mol, compared to the reference antidiabetic drug pioglitazone (PubChem ID: 4829; -8.759 kcal/mol ΔGbind = -96.81 kcal/mol)...Structural analyses, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), hydrogen bond interactions, principal component analysis (PCA), free energy landscape (FEL), and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) binding energy calculations analysis, indicated stable binding behavior of the PPARγ-oleic acid complex throughout the simulation. These findings suggest that oleic acid may act as a potential natural modulator of PPARγ, highlighting the therapeutic potential of traditional rice varieties as sources of antidiabetic bioactive compounds.

P3, N=1000, Active, not recruiting, Inventiva Pharma | Trial completion date: Jun 2027 --> Sep 2027 | Trial primary completion date: Jun 2027 --> Sep 2027

P1/2, N=30, Completed, Vivacell Biotechnology Espana S.L. | Not yet recruiting --> Completed

P3, N=606, Completed, Celltrion | Active, not recruiting --> Completed

P3, N=1000, Active, not recruiting, Inventiva Pharma | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2026 --> Jun 2027

P3, N=102, Active, not recruiting, Zydus Therapeutics Inc. | Recruiting --> Active, not recruiting | N=150 --> 102

P=N/A, N=3550, Not yet recruiting, Chipscreen Biosciences, Ltd.