Celastrol

Celastrol (Tripterine;Tripterin) is a proteasome inhibitor which potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome with IC₅₀ of 2.5 μM. In addition, Celastrol is also an antibiotic with potent antimicrobial activity against standard and clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, inducing oxidative stress and inhibiting DNA synthesis by binding to P5CDH^[1][2][3]. IC50 & Target:IC50: 2.5 μM (20S proteasome)^[1] In Vitro:Celastrol (Tripterine;Tripterin) significantly inhibits the proteasomal chymotrypsin activity in PC-3 cells in a concentration-dependent manner; at 2.5 μM it reaches ~55% inhibition, comparable to its potency to a purified 20S proteasome (IC₅₀=2.5 μM). Furthermore, increased levels of IκB-α, Bax, and p27 are observed, three well known target proteins of the proteasome in PC-3 cells treated with Celastrol^[1]. In Vivo:Treatment of PC-3 tumor-bearing nude mice with Celastrol (1-3 mg/kg/d, i.p., 1-31 days) results in significant inhibition (65-93%) of the tumor growth^[1]. Following treatment with 3 and 6 mg/kg Celastrol, the levels of malondialdehyde (MDA) are significantly decreased by 35.2 and 36.7% (P<0.05), respectively. Treatment with 3 and 6 mg/kg Celastrol markedly restores the GSH level (P<0.05) to almost normal levels^[2].