Lys01 (trihydrochloride)

1391426-24-6

C23H26Cl5N5

H2O : 6.4 mg/mL (11.64 mM; Need ultrasonic); DMSO : 75 mg/mL (136.43 mM; Need ultrasonic)

Autophagy

Lys01 trihydrochloride (Lys05) is a novel lysosomal autophagy inhibitor with IC₅₀ values of 3.6, 3.8, 6 and 7.9 uM for 1205Lu, c8161, LN229 and HT-29 cell line in the MTT assay. IC50 & Target: IC50: 3.6 uM (1205Lu), 3.8 uM (c8161), 6 uM (LN229), 7.9 uM (HT-29)^[1] In Vitro: Lys01, is a 10-fold more potent autophagy inhibitor than HCQ. Compared with HCQ, Lys05, a water-soluble salt of Lys01, more potently accumulates within and deacidifies the lysosome. Lys01 and lys01 trihydrochloride produce equivalent dose-dependent increases in the LC3II/LC3I ratio, accumulation of the autophagy cargo protein p62, and identical IC₅₀ values in the MTT assay^[1]. In Vivo: With this high-dose, short-term treatment, no mice die, but after 2 d of dosing, mice treated with lys01 trihydrochloride 76 mg/kg i.p. are observed to have arched backs and lethargy. Morphologically, EM show that cells with intact nuclear and cytoplasmic membranes contain large AVs in lys01 trihydrochloride-treated tumors. Tumor growth is significantly impaired in lys01 trihydrochloride-treated tumors compared with controls. Lys01 trihydrochloride treatment results in a 53% reduction in the average daily tumor growth rate compared with vehicle-treated controls. A significant three- and six-fold accumulation of AV is observed at the end of 14 d of treatment in HCQ- and lys01 trihydrochloride-treated tumors, respectively, compared with control-treated tumors^[1].