Soliman, Ghada A.; Shukla, Surendra K.; Etekpo, Asserewou; Gunda, Venugopal; Steenson, Sharalyn M.; Gautam, Nagsen; Alnouti, Yazen; Singh, Pankaj K. published the artcile< The synergistic effect of an ATP-competitive inhibitor of mTOR and metformin on pancreatic tumor growth>, Application of C24H15F3N4O, the main research area is pancreatic tumor mTOR metformin.
We investigated the impact of inhibition of mTORC1/mTORC2 and synergism with metformin on pancreatic tumor growth and metabolomics. Cell lines derived from pancreatic tumors of the KPC (KrasG12D/+; p53R172H/+; Pdx1-Cre) transgenic mice model were implanted into the pancreas of C57BL/6 albino mice (n = 10/group). Two weeks later, the mice were injected i.p. with daily doses of 1) Torin 2 (mTORC1/mTORC2 inhibitor) at a high concentration (TH), 2) Torin 2 at a low concentration (TL), 3) metformin at a low concentration (ML), 4) a combination of Torin 2 and metformin at low concentrations (TLML), or 5) DMSO vehicle (control) for 12 d. Tissues and blood samples were collected for targeted xenometabolomics anal., drug concentration, and cell signaling. Metabolomic anal. of the control and treated plasma samples showed differential metabolite profiles. Phenylalanine was significantly elevated in the TLML group compared with the control (+426%, P = 0.0004), whereas uracil was significantly lower (-38%, P = 0.009). The combination treatment reduced tumor growth in the orthotopic mouse model. TLML significantly decreased tumor weights (0.66 ± 0.08 g; 52%) compared with the control (1.28 ± 0.19 g; 100%) (P < 0.002). The combination of mTOR dual inhibition by Torin 2 and metformin is associated with an altered metabolomic profile and a significant reduction in pancreatic tumor burden compared with single-agent therapy, and it is better tolerated. Current Developments in Nutrition published new progress about Pancreatic neoplasm. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Application of C24H15F3N4O.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem