P1, N=28, Not yet recruiting, Chipscreen Biosciences, Ltd.

Thiazolidinedione agonists (pioglitazone, rosiglitazone) have modest but clinically significant anti-psoriatic efficacy when combined with traditional systemic medicines, resulting in cardiometabolic benefits. Future directions include patient biomarker stratification, dual/selective agonists (glitazars), and sensible combination with biologics that target tumor necrosis factor-alpha/IL-17/IL-23. This review reframes PPARs as key players in the relationship between psoriasis and metabolic syndrome by synthesizing molecular understanding and clinical data.

Intranasal IL-4 delivery may represent a promising therapeutic strategy for enhancing white matter integrity in leukodystrophies and MS. Abbreviations: MS, multiple sclerosis; IL-4, Interleukin 4; CNS, central nervous system; OPCs, oligodendrocytes precursor cells; IL-4R, IL-4 receptor; i.n., intranasal; LPC, lysophosphatidylcholine; PVL, periventricular leukomalacia; EAE, experimental autoimmune encephalomyelitis; dpi, days post immunization; dpl, days post lesion; Nkx2.2, NK2 homeobox 2; Olig2, oligodendrocyte transcription factor 2; OLs, oligodendrocytes; SOX10, SRY-Box Transcription Factor 10; PDGFRα, platelet derived growth factor receptor alpha; CNPase, 2',3'-Cyclic Nucleotide 3' Phosphodiesterase; APC, adenomatous polyposis coli; ASPA, aspartoacylase; GFAP, glial fibrillary acidic protein; Iba1, ionized calcium binding adaptor molecule 1; MBP, myelin basic protein; TEM, transmission electron microscopy; CC, corpus callosum; GCC, genu of the corpus callosum; CG, cingulum; CTX, cortex; STR, striatum; EC, external capsule; Pre-OLs, pre-myelinating oligodendrocytes; STAT6, signal transducer and activator of transcription 6; Pio, pioglitazone; T3, triiodothyronine; CNTF, ciliary neurotrophic factor; PPARγ, peroxisome proliferator-activated receptor γ.

MitoNEET (CDGSH iron-sulfur domain-containing protein 1) is an outer mitochondrial membrane protein that was recently discovered as an off-target of the antidiabetic drug pioglitazone, and plays an essential role in mitochondrial bioenergetics, mitophagy, and iron metabolism...In this review, we will evaluate the state of the field in the development of NEET protein interacting ligands, which can serve as pharmacological tools to study the biology/biochemistry of NEET family proteins in disease. The NEET family represents a novel class of drug targets, enabling the development of novel treatment modalities to modulate disease progression in various human disorders.

P2, N=61, Completed, The University of Texas Health Science Center, Houston | Recruiting --> Completed | Trial completion date: Feb 2026 --> Oct 2025 | Trial primary completion date: Feb 2026 --> Sep 2025

P3, N=24, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Initiation date: Jan 2026 --> Jul 2026

P1, N=14, Completed, Dana-Farber Cancer Institute | N=28 --> 14 | Trial completion date: Jan 2016 --> Jan 2026

P3, N=1000, Active, not recruiting, Inventiva Pharma | Recruiting --> Active, not recruiting | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Dec 2026

Here, we show that combining the PI3Kδ inhibitor linperlisib with the pan-peroxisome proliferator-activated receptor (PPAR) agonist chiglitazar, an agent that reprograms tumor metabolism, delivers robust antitumor activity across FL models, including cell-derived and patient-derived xenografts, with a favorable tolerability profile. Compared with monotherapy, the combination consistently achieves superior tumor control in vivo without overt toxicity, supporting its clinical translation potential. Collectively, these data provide a mechanistic rationale for dual targeting of PI3Kδ and PPARα in FL and advocate for clinical evaluation of this combination with FoxO1 as a pharmacodynamic biomarker.

P4, N=133, Completed, Celltrion Pharm, Inc. | Active, not recruiting --> Completed

P1, N=64, Recruiting, The University of Texas Health Science Center at San Antonio | Initiation date: Feb 2026 --> Jul 2026

Western blots using a PPARγ agonist (pioglitazone) and antagonist (T0070907) validated its crucial role in mediating compound 20-induced apoptosis in HepG2 cells...Furthermore, a CETSA assay provided additional support, confirming that compound 20 enhances PPARγ's thermal stability. Collectively, these findings strongly suggest that compound 20 inhibits HepG2 proliferation and promotes HepG2 apoptosis via PPARγ modulation, positioning it as a promising lead compound for hepatocellular carcinoma treatment.