amuvatinib (MP470)

In silico drug screening identified 6 effective compounds for high-risk CAFs-related LUSC: TAK-715, GW 441756, OSU-03012, MP470, FH535, and KIN001-266. Additionally, search tool for interaction of chemicals database highlighted PI3K-Akt signaling as a potential target pathway for high-risk CAFs-related LUSC. Overall, our findings provide a molecular classifier for high-risk CAFs-related LUSC and suggest that treatment with PI3K-Akt signaling inhibitors could benefit these patients.

This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

Additionally, we obtained three potentially effective drugs for OS: erlotinib, MP470, and WH-4-023 targeting the PI3K-Akt pathway. The expression level of ZNF37BP was significantly elevated in OS cell lines than in normal osteoblast hFOB1.19 cells, and that of ATP7A, LIPT1, AL353759.1, and AC005034.5 were decreased considerably in OS cell lines. Cuproptosis-related lncRNAs are correlated with the CAFs of osteosarcoma, and this could serve as a foundation for OS survival prediction and treatment.

Moreover, an increased apoptotic rate was observed when the GBM-derived U87MG cells were co-treated with LPS and Temozolomide (TMZ) in comparison to TMZ alone. Moreover, the combined treatment with the RAD51 inhibitor, Amuvatinib in combination with, TMZ after LPS stimulation reduced tumor cell viability more than with each treatment alone. In conclusion, our results suggest that stimulation of TLR4 combined with pharmacological inhibition of the DNA repair pathway may be an alternative treatment for GBM patients.