TG 100-115

Curcumin did not sensitize HepG2-DR cells to doxorubicin, whereas verapamil and simvastatin enhanced doxorubicin cytotoxicity only at toxic concentrations. In contrast, several TKIs, including nilotinib, tivozanib, and, to a lesser extent, cabozantinib, exhibited synergistic effects with doxorubicin in HepG2-DR cells...Third-generation MDR1 inhibitors (tariquidar, elacridar, and zosuquidar) sensitized HepG2-DR and HB-303 cells at non-toxic nanomolar concentrations in vitro...MDR1 inhibitors, such as zosuquidar, may enable dose reductions of chemotherapeutic agents, whereas the use of synergistic TKIs, such as tivozanib, may improve therapeutic outcomes and minimize adverse effects in children with HB. TG100-115, a TRPM7 kinase inhibitor, provides neuroprotection and attenuates NLRP3 inflammasome-mediated neuroinflammation in a neonatal mouse model of hypoxic-ischemic brain injury.

The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumour effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types.

Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN‑induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment.

Furthermore, we showed that the synergistic interaction might be associated with TRPM7 channel activities using combination treatments of TRAIL and TRPM7 inhibitors (NS8593 as a TRPM7 channel inhibitor and TG100-115 as a TRPM7 kinase inhibitor). We reveal that downregulation of cellular FLICE-inhibitory protein via inhibition of Ca influx might be involved in the synergistic interaction. Our study would provide both a new role of TRPM7 in TNBC cell apoptosis and a potential combinatorial therapeutic strategy using TRPM7 inhibitors with TRAIL in the treatment of TNBC.