Germanin (suramin)

The broad-spectrum P2 receptor antagonist, suramin, P2X7 receptor-specific antagonist, oATP, P2Y6 receptor-specific antagonist, MRS 2578, and P2Y12 receptor-specific antagonist, AR-C 69931, all showed significant arrest in tumor growth...Disaggregated cells from AR-C 69931-treated tumors, when injected intravenously in naïve mice, did not exhibit metastasis in various tissues which was observed in mice injected with cells from saline-treated tumors. Our results show that blocking of P2 receptors is a therapeutic alternative to inhibit COX-2 expression, and thereby, arrest tumor progression and metastasis.

Suramin dramatically inhibited NIH ligation in the left common carotid artery (LCCA) vivo. Therefore, our results indicate that suramin protects against the development of pathological vascular remodelling by attenuating VSMCs proliferation, migration, and phenotypic transformation and may be used as a potential medicine for the treatment of NIH.

P=N/A, N=20, Not yet recruiting, The First Affiliated Hospital of Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine | Phase classification: P1 --> P=N/A

Suramin could inhibit NLRP3/caspase-1/GSDMD canonical pyroptosis pathway in LPS-induced MH-S alveolar macrophages.

Finally, we suggested the top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, and TG.02) for the treatment of BC by molecular docking analysis with the proposed HubGs-mediated receptors. Molecular docking analysis results also showed that these drug molecules may inhibit cancer-related post-translational modification (PTM) sites (Succinylation, phosphorylation, and ubiquitination) of hub proteins. This study's findings might be valuable resources for diagnosis, prognosis, and therapies at an earlier stage of BC.

Importantly, the most active compound, 6-methoxy-4',6'-dimethylisoflavone-2',5'-quinone (39) displayed SIRT1 inhibitory activity comparable to that of the reference compound, suramin. The in silico docking simulations in the active site of SIRT1 further substantiated the experimental results and explored the binding orientations of potent compounds in the active site of the target.

Lidocaine (10 mM; a concentration within the clinically used range) activates T2R calcium responses that are inhibited by pertussis toxin, an inhibitor of G - coupled GPCRs, and by suramin, an inhibitor of G . This was distinct from the structurally-related T2R agonist denatonium, which activates calcium responses inhibited by G inhibitor YM-254890 but not pertussis toxin...Lidocaine or other T2R agonists may aid in eradication of residual cancer cells and extend time between initial surgery and reoccurrence/metastasis as an alternative or complementary therapy. With their promising effects on oral and oropharyngeal SCC cells and accessibility of the oral cavity to topically applied lidocaine gels, further work is warranted to understand the effects of bitter local anesthetics and T2R signaling in HNSCC and normal surrounding epithelia.

In vitro, suramin or P2Y2R silencing effectively inhibited the phosphorylation of EGFR and ERK1/2, similar to the down-regulated effects of their corresponding inhibitors (EGFR inhibitor AG1478 and ERK1/2 inhibitor U0126) accompanied by reduced levels of TNF-α and IL-1β compared to alcohol-induced AML-12 cell. In addition, we found that silencing P2Y2R attenuated the apoptosis of hepatocyte. Our findings suggest that P2Y2R regulates alcoholic liver inflammation by targeting the EGFR-ERK1/2 signaling pathway and plays an important role in hepatocyte apoptosis, which may provide new ideas for the development of methods to treat ALD.

The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.

Preconditioning with an inulin-supplemented diet for 2 weeks significantly reduced hepatic adenosine triphosphate (ATP) content; suramin, a purinergic P2 receptor antagonist, abolished the protective effect... There is a possible unraveled etiopathophysiological link between the maintenance of liver tolerance and dietary fiber. The SCFA-PPARγ-UCP2 axis may provide therapeutic targets for immune-mediated liver injury in the future.

In this study, the effect of 5-FU on SIRT5 and FOXO 3a proteins was determined for the first time in HCT-116 p53 +/+ and HCT-116 p53 -/- cells. These results may help the discovery of new markers in colon cancer treatment.

These findings not only demonstrate a potential biological mechanism between aberrant SUMOylation, genomic instability and cancer metastasis, but also provide a promising biomarker aiding in stratifying ESCC individuals with different prognosis, as well as a potential therapeutic target MCM10.

Among all the compounds 8 L, 8q, 9n and 9p showed higher inhibitory activity on the viability of HL 60 than the standard methotrexate...TNFα and Leptin as compared to the standard suramin, while 9p has activity comparable to suramin against IGF1, VEGF, FGFb, and Leptin...Additionally, we present in silico molecular docking data to provide the structural rationale of observed TNFα inhibition against newly synthesized compounds. Overall, the synthesized flutamide derivatives have not only anticancer activity, but also possess dual inhibitory effect (anti-angiogenesis and antioxidant) and hence can act as a promising avenue to develop further anticancer agents.

Simultaneous administration of high-dose but not low-dose suramin to the cisplatin-treated rats improved the deleterious morphological and morphometrical effects on RPTCs and restored the aforementioned biochemical parameters to control values. In conclusion suramin in a dose dependant manner protects RPTCs from damage induced by cisplatin.