R-(-)-gossypol (AT 101)

Moreover, Gossypol exhibited cytotoxic effects on human breast, prostate, and colorectal cancer cell lines, at least partially through downregulating the oncogenic substrates of targeted DUBs such as c-Myc, Mcl-1, MDM2, and Cyclin D1. Collectively, our findings position Gossypol as a promising small-molecule inhibitor targeting DUBs, especially USPs, and provide a rationale for further exploring its therapeutic potential in USP-driven cancers.

KEGG analysis suggested that the toxic mechanisms may be linked to pathways involved in malignancy, the HIF-1 signaling pathway, proteoglycans in cancer, apoptosis, and others. Gossypol demonstrates a significant therapeutic effect against cervical cancer; however, its hepatotoxicity risk, mediated through multiple targets and pathways, requires further investigation.

Crucially, we demonstrate that gossypol binding reduces the overall flexibility of the binding site and that each binding state is characterized by a unique pattern of conformational stabilization across the four pockets. These findings provide an unprecedentedly detailed and dynamic roadmap of the gossypol-Bcl-2 interaction, offering crucial insights for the future structure-based design of next-generation inhibitors.

Collectively, these modulators demonstrate PPI druggability and provide chemical probes and lead scaffolds for therapeutic development in cancer, neurodegeneration, infectious disease, and immune disorders.

The three natural products showed potent to significant activity, effectively inducing apoptosis in the HL-60 cell line. Hence, this study identifies three potential lead candidates for drug discovery against Bcl-2-related cancers after further mechanistic and pre-clinical studies.

Our study uncovers a "C1orf35-driven" energy metabolism model in MM cells, providing new insights into the pathogenesis of MM and a potential novel target for the treatment of cancer cells with a high"C1orf35-driven" anabolic metabolism. Schematic diagram of C1orf35 simultaneously promotes glycolysis and OXPHOS.

GT exerts synergistic anti-HCC effects through a dual mechanism: directly suppressing tumor proliferation by inactivating the PI3K/AKT pathway, and remodeling the TIME by targeting FASN-dependent lipid metabolism in Tregs. These findings highlight the potential of GT as a novel multitargeted agent for HCC treatment.

P1, N=20, Not yet recruiting, The Second Hospital of Hebei Medical University; The Second Hospital of Hebei Medical University

To inhibit SRC activity, natural compounds (e.g., gossypol, bufalin, verrucarin A) and synthetic small molecules (e.g., SI-2, SI-12, MCB-613) have been developed, demonstrating preclinical efficacy across several human diseases...This review summarizes current knowledge of SRC biology in benign gynecologic disorders, outlines their mechanistic roles in disease progression, and highlights opportunities for clinical translation. Targeting SRCs may ultimately represent a novel, non-hormonal, fertility-preserving therapeutic strategy in women's health.

This study also describes differential responses of TNBC cell lines to polyphenol treatment, highlighting the importance of considering genetic variability in therapeutic strategies, as well as the importance of the interaction of polyphenols with the gut microbiome, which may establish the bioavailability and effectiveness of these compounds toward therapeutic outcomes. Further preclinical and clinical studies are warranted to fully elucidate the therapeutic potential of polyphenols and translate these findings into clinical practice, thereby improving outcomes for patients with TNBC worldwide.

= 28.44), surpassing celecoxib. Molecular docking and dynamics confirmed strong and stable binding to Mcl-1 and COX-2. In silico ADMET predictions indicated favorable drug-like and pharmacokinetic properties for the active compounds.

Administration of (±)-gossypol (40 mg/kg/day ip) for five consecutive days was well tolerated, with no observable signs of systemic toxicity, such as >5 % weight loss or behavioral abnormalities on mice. These findings revealed that (±)-gossypol, in addition to its tumor suppressive effect, can inhibit pro-angiogenic effects of Ehrlich's ascites carcinoma (EAC) cells and have a protective effect in breast cancer.