20S Proteasome-IN-2

20S Proteasome-IN-2 is a human 20S proteasome inhibitor. 20S Proteasome-IN-2 shows high selectivity to its β5 subunit with the IC50 of 0.18 μM. 20S Proteasome-IN-2 displays anti-proliferative effect in vitro and in vivo, and arrests cell cycle at G2/M[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

IC50: 0.18 μM (β5 subunit of 20S Proteasome)

20S Proteasome-IN-2 (compoun 11m) inhibits 20S proteasome by forming no irreversible covalent modification on it[1]. 20S Proteasome-IN-2 (compoun 11m) (1.56, 3.13, 6.25, 12.5, and 25 μM) shows high binding affinity with purified human 20S proteasome, the equilibrium dissociation constants is 4.8 μM[1]. 20S Proteasome-IN-2 (compoun 11m) (0-1.5 μM; 24 hours) inhibits tumor cells in a low concerntration with IC50 values of 0.88, 0.77, 0.67, 0.73, 1.3, 0.57, and 0.28 μM for A375, BGC-823, Hela, HT-29, A549, PCM1E8, HCT-116, resepectively[1]. 20S Proteasome-IN-2 (compoun 11m) (0-1.5 μM; 24 hours) arrests the cell cycle at G2/M[1]. Cell Cycle Analysis[1] Cell Line: Human colorectal cancer cell line HCT-116 cells Concentration: 1 μM Incubation Time: 24 hours Result: Arrested the cell cycle at G2/M.

20S Proteasome-IN-2 (compoun 11m) is (i.v.; 5 mg/kg; single injection) rapidly cleared from the plasma with an average terminal plasma half-life of 14 min, thus it exhibits extensive tissue permeability and low clearance rate (CL) of 2.0 L/h/k, and is largely eliminated extrahepatically[1]. 20S Proteasome-IN-2 (compoun 11m) (i.v.; 10 mg/kg; twice one week; 4 weeks) shows antitumor efficacy combat solid tumors[1]. Pharmacokinetic parameters of 20S Proteasome-IN-2 (compoun 11m)[1] Administrations Cmax (μg/L) AUC0-t (μg/L•h) T1/2 (min) MRT (min) CL (L/h/kg) Vss (L/kg) iv, 5 mg/kg 2007 680 13.83 20.20 2.0 0.66 Animal Model: HCT-116 cell xenograft nude mice model[1] Dosage: 10 mg/kg Administration: Intravenous injection; twice weekly for consecutive four weeks Result: Inhibited tumor growth in vivo and was well tolerated.

[1]. Sun Q, et al. Design and synthesis of tripeptidyl furylketones as selective inhibitors against the β5 subunit of human 20S proteasome. Eur J Med Chem. 2020 Apr 15. 192:112160.