Biological Activity
M2698 (MSC2363318A) is an orally active, ATP competitive, selective p70S6K and Akt dual-inhibitor with IC50s of 1 nM for p70S6K, Akt1 and Akt3. M2698 can cross the blood-brain barrier and has anti-cancer activity[1].
In Vitro
M2698 (0.3 nM to 50 M; 72 hours) inhibits proliferation in a dose-dependent manner in breast tumors cell lines with IC50s of 0.02-8.5 µM[1]. M2698 (0.3, 1 µM; 24 hours) inhibits p70S6K activity and induces feedback loop phosphorylation on Akt and suppresses Akt activity in breast cancer cell lines[1]. M2698 inhibits indirectly pGSK3β (IC50=17 nM) and pS6 (IC50=15 nM)[1]. Cell Proliferation Assay[1] Cell Line: Breast tumors cell lines Concentration: 0.3 nM to 50 M Incubation Time: 72 hours Result: Inhibited proliferation in a dose-dependent manner. Western Blot Analysis[1] Cell Line: HCC1419 and MDA-MB-453 cells Concentration: 0.3, 1 µM Incubation Time: 24 hours Result: Inhibited p70S6K activity and induced feedback loop phosphorylation on Akt and suppressed Akt activity in breast cancer cell lines.
In Vivo
M2698 (10-30 mg/kg/day; PO; 28 days) results in dose-dependent inhibition of tumor growth and results in tumor regression with the highest dose of 30 mg/kg[1]. M2698 (20 mg/kg/day; PO; 4 days) has a tumor:plasma exposure ratio of 12:1 over 24 hours and leads to increased levels of pAkt in tumor tissue[1]. The mean total concentration of M2698 after 16-hour infusion in rats is 1750 ng/g and 175 ng/mL in brain and plasma, respectively[1]. M2698 (po; 1, 5, 10, or 20 mg/kg/day; for 7 days) inhibits the phosphorylation of S6 in a dose-proportional manner over time after a single administration or daily treatments over 7 days[1]. Animal Model: Female nude mice bearing MDA-MB-468 tumors[1] Dosage: 10, 20 and 30 mg/kg Administration: PO; daily; for 28 days Result: Resulted in dose-dependent inhibition of tumor growth and resulted in tumor regression with the highest dose of 30 mg/kg. Animal Model: Female SCID Beige mice with MDA-MB-453 xenografted[1] Dosage: 20 mg/kg (Pharmacokinetic Analysis) Administration: Daily; for 4 days Result: Had a tumor:plasma exposure ratio of 12:1 over 24 hours.
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
