Zepsun (donafenib)

The HCC cells HepG2 and SNU449 were treated with five drugs, namely, dimethyl sulfoxide, AZ-628, SU-5402, TG-101209, and SPP-86, combined with donafenib to determine half-maximal inhibitory concentration values...Ferrous ion (Fe2+) and reactive oxygen species levels were measured after Erastin/RSL3 induction...In vivo experiments demonstrated a combined anti-tumor efficacy of AZ-628 and donafenib in HCC models (P < 0.0001). The findings of this study reveal a new combination therapy targeting the TK pathway for the treatment of HCC and provide a theoretical foundation for addressing donafenib resistance.

P2, N=34, Not yet recruiting, Jinling Hospital, China

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P=N/A, N=78, Recruiting, Fujian Cancer Hospital; Fujian Cancer Hospital

P2, N=35, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

This suggests a novel combinatorial strategy that targets ferroptosis through NF-κB inhibition. Further research is needed to translate these promising results into clinical practice.

P=N/A, N=30, Not yet recruiting, Beijing Youan Hospital, Capital Medical University; Beijing Youan Hospital, Capital Medical University

P=N/A, N=56, Recruiting, Maoming People's Hospital; Maoming People's Hospital

Our study demonstrates that Kindlin-1 significantly influences HCC progression by regulating mitophagy through the PINK1/Parkin pathway. Inhibiting Kindlin-1 may represent a promising therapeutic strategy to enhance the efficacy of donafenib, thereby providing novel insights into improving treatment outcomes for HCC patients.

Lenvatinib demonstrates superior survival outcomes compared to donafenib as a conversion therapy in patients with CNLC stage I-III HCC. While the two therapies are comparable in overall safety profiles, lenvatinib is more tolerated, with a lower incidence of severe adverse events.

We further show that the small-molecule inhibitor chidamide downregulates RIOK1 and enhances TKI efficacy. RIOK1-positive stress granules are found in donafenib-resistant tumors from patients with HCC. These findings reveal a link between stress granule dynamics, metabolic reprogramming and HCC progression, offering the potential means to improve TKI efficacy.

Notably, Donafenib induces mitochondrial fragmentation and reduces mitochondrial length by increasing the expression of DRP1, without affecting Mfn1 or Mfn2. Silencing of DRP1 protects against mitochondrial dysfunction induced by Donafenib, indicating that DRP1 plays a key role in mediating Donafenib's effects on mitochondrial function in HCC cells.