Notably, landmark clinical progress has been achieved: The catalytic nanocrystal suspension CNM-Au8, a therapeutic candidate for amyotrophic lateral sclerosis, has advanced to phase II clinical trials. This review systematically summarizes the core catalytic mechanisms of antioxidant nanozymes, clarifies the structure-activity relationships between rational material design and catalytic performance, reviews the latest advances in their biomedical applications, and dissects the key bottlenecks restricting preclinical research and clinical translation. It aims to provide rational design principles for researchers in this field, reduce empirical trial and error in material development, and provide guidance for the further optimization and clinical translation of antioxidant nanozymes.

P1, N=16, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

P2, N=30, Not yet recruiting, HighField Biopharmaceuticals Corporation

In murine toxicology studies, R-5780 was well tolerated, with no adverse events or systemic inflammation observed following oral administration. Together, these results identify R-5780 as a safe and potent NOD2 activator that synergizes with PD-1 blockade to enhance antitumor immunity and support its advancement toward clinical evaluation.

This study preliminarily elucidates the multi-target synergistic anti-inflammatory effects of PLSL from the perspectives of inflammatory signaling pathways and gut microbiota. It provides experimental evidence for the whole-plant development and utilization of Platycodon grandiflorum and Lonicera japonica as ethnomedicines.

P2, N=146, Recruiting, Jinling Hospital, China

Although inhibition of autophagy with hydroxychloroquine and related lysosomal inhibitors has provided proof of concept, their limited specificity has motivated the development of more selective approaches, such as Unc-51-like autophagy activating kinase 1 (ULK1) inhibitors and selective autophagy receptor-directed strategies. Emerging combination regimens that integrate autophagy blockade with KRAS/extracellular signal-regulated kinase (ERK) pathway inhibition, metabolic stress, or immune checkpoint blockade may help overcome chemoresistance and enhance anti-tumor immunity. Together, these advances underscore the therapeutic promise of targeting metabolic plasticity and autophagy in PDAC and lay the groundwork for rational next-generation combination strategies.

P2, N=53, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Jan 2026 --> Jan 2027

P1, N=31, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=0, Withdrawn, Ankyra Therapeutics, Inc | N=20 --> 0 | Not yet recruiting --> Withdrawn

METTL3 increases the mRNA stability of the intrinsic immune checkpoint SIRPA by activating IGF2BP2 in an m6A-dependent manner, which subsequently increases its protein expression and suppresses the phagocytosis of macrophages both in vivo and in vitro. In conclusion, CHA is a candidate inhibitor compound that targets the METTL3-SIRPA axis through enhancing the phagocytic function of macrophages and is thus a promising therapy for treating colon cancer.

Together, these data demonstrate that (CAR) T-cell-mediated killing of lymphoma cells has a necroptotic arm which is correlated with modulation of the wider immune response. They imply that manipulation of the apoptotic versus necroptotic balance in immunotherapy could affect engagement of the autologous immune response.