P2, N=12, Suspended, National Neuroscience Institute | Not yet recruiting --> Suspended

We summarize the clinical translation progress of ACT001, including its safety and pharmacokinetic profiles, discuss emerging delivery systems such as micelles, and review the patent landscape of PTN derivatives. By integrating mechanistic insights with progress in clinical applications and drug delivery, this review provides a foundation for further mechanistic studies and supports the translational development of PTN-based therapies for respiratory disorders.

P1, N=18, Recruiting, Oncozen Co., Ltd | Not yet recruiting --> Recruiting

Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts oxidative phosphorylation and induces ferroptosis, providing a strong rationale for combination strategies with PARP inhibitors to overcome drug resistance.

P1, N=36, Completed, Otsuka Pharmaceutical Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Jan 2026

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

Furthermore, CDDO-Me did not compromise the antitumor efficacy of DOX/LAP in breast cancer cells. CDDO-Me protects against DOX/LAP-induced cardiotoxicity by stabilizing GPX4 and inhibiting ferroptosis, offering a promising therapeutic strategy that preserves cardiac function without interfering with chemotherapy.

These findings identify Niclosamide as a potent dual STAT1/STAT3 inhibitor capable of reversing IFN-γ- and hypoxia-driven immune evasion. Repurposing Niclosamide may represent a promising strategy to enhance the efficacy of immune checkpoint blockade in solid tumors.

Notably, 8 exhibited significant antitumor efficacy comparable to CDDO-Me (bardoxolone methyl), which had entered clinical trials. Taken together, 8 represents a promising candidate for the treatment of cancer and merits further study.

TAMs enhanced the proliferation, invasion, and migration of PC3 cells, but these effects were suppressed by the STAT3 inhibitor WP1066 and IL-6 neutralizing antibodies...IL-6 increased the activation of JAK2 and STAT3 proteins in PC3 cells, which was reduced by both treatments. These findings underscore the role of TAMs in promoting prostate cancer progression through IL-6-mediated JAK2/STAT3 signaling, suggesting the potential of targeting this pathway as a therapeutic strategy for advanced prostate cancer.

P1, N=132, Terminated, Vividion Therapeutics, Inc. | Trial completion date: Jan 2027 --> Dec 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Dec 2025; The study has ended

Molecular docking analyses supported the binding of CUR and DOX to key ferroptosis regulators. This study shows the potential of CUR to sensitize DOX-resistant cancer cells through ferroptosis-linked-oxidative stress targeting.