Notably, 7-methoxyheptaphylline markedly suppressed STAT3 phosphorylation in a concentration-dependent manner, comparable to the STAT3 inhibitor JSI-124...Collectively, our results demonstrate that C. harmandiana exerts broad-spectrum anticancer activity through coordinated modulation of the JNK-STAT3 axis, leading to caspase-dependent apoptosis. These findings highlight its potential as a promising candidate for the development of STAT3-targeted anticancer therapies.

P1/2, N=48, Active, not recruiting, Accendatech USA Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2a --> P1/2 | Trial completion date: Nov 2023 --> Dec 2026

Subsequent in vitro experiments demonstrated that CuI treatment upregulated SDHA expression and inhibited activation of the NF-κB pathway. Collectively, these findings suggest that the identified PBs may serve as early-warning indicators for stage I COAD patients and that CuI suppresses COAD cell proliferation, potentially through the SDHA/NF-κB axis, highlighting its promise as a potential therapeutic candidate.

These modified compounds can be tested to determine which are most effective on cancer treatment. These findings are important in the development of multi-functionalized niclosamide and drug design therapy in the future.

Furthermore, it reduced the p-STAT3/STAT3 ratio and decreased PD-L1 and c-Myc expression in tumor tissues. SS exerts potent anti-NSCLC effects by blocking the STAT3/PD-L1 signaling pathway and suppressing EMT, suggesting its potential as a therapeutic agent for NSCLC.

These effects were effectively reversed by the stemness inhibitor Napabucasin...In summary, this study reveals that PMN-MDSCs can activate the STAT3-CXCL5-ERK positive feedback regulatory axis via exosomal S100A9, synergistically enhancing breast cancer cell stemness and metastatic capacity. These findings provide a theoretical reference and potential intervention targets for targeting the tumor microenvironment to inhibit TNBC progression.

Moreover, we identified ACT001 as a novel USP22 inhibitor, and ACT001 induced substantial ERK1/2 ubiquitination and its subsequent degradation, efficiently suppressing the growth of CRC cells in vitro and in vivo by targeting USP22. Overall, this study revealed the mechanism underlying the role of hyperregulated ERK1/2 in CRC development, providing further insights into the pathology of CRC and the potential applicability of USP22-ERK1/2 as a therapeutic target in CRC.

P2/3, N=210, Recruiting, Hyundai Bioscience Co., Ltd.

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 OxPhos and induces ferroptosis, providing a strong rationale for combination strategies with PARPis to overcome drug resistance.

S1P/STAT3/Shh/Gli1/FoxM1 pathway plays an important role in PASMCs proliferation and pulmonary arterial remodeling. Targeting this cascade may have potential value for the management of PAH.

These findings indicate that combined curcumin and doxorubicin induce apoptosis primarily through JNK-dependent MAPK signaling, accompanied by stress-associated cellular responses.

This paper summarizes the current mechanistic insight and disease-specific evidence regarding MCL/ACT001 and further evaluates their therapeutic repositioning potential for age-related diseases, including cardiovascular and cerebrovascular diseases, fibrotic conditions, immune disorders, metabolic diseases, and tumors. Additionally, we discussed key translational challenges.