Aclacinomycin A

Aclacinomycin A (aclarubicin) is an anthracycline anticancer agent with demonstrated activity against both leukemias and solid tumors. Aclacinomycin A is the first described non-peptidic inhibitor showing discrete selectivity for the chymotrypsin-like activity of the 20 S proteasome. Aclacinomycin A significantly decreases hydrolysis of Z-E(OtBu)AL-pNA by MPC or by chymotrypsin with IC50 of 18 μM and 24 μM, respectively. Aclacinomycin A (1 μM), in combination with doxorubicin, increases cytotoxic activity of doxorubicin against K562 resistant cells. Aclacinomycin A (1 μM) partly blocks the doxorubicin efflux in resistant cell nuclei of K562 tumour cells, resulting in enhanced accumulation of doxorubicin.