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Identification of ML-9 as a Lysosomotropic Agent Targeting Autophagy and Cell Death

Identification of ML-9 as a Lysosomotropic Agent Targeting Autophagy and Cell Death

A Kondratskyi, M Yassine, C Slomianny, K Kondratska, D Gordienko, E Dewailly, V Lehen'kyi, R Skryma, N Prevarskaya

Cell Death Dis. 2014 Apr 24;5(4):e1193.

PMID: 24763050

Abstract:

The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' compound that stimulates autophagosome formation (by downregulating Akt/mammalian target of rapamycin (mTOR) pathway) and inhibits their degradation (by acting like a lysosomotropic agent and increasing lysosomal pH). We show that ML-9 as a monotherapy effectively induces prostate cancer cell death associated with the accumulation of autophagic vacuoles. Further, ML-9 enhances the anticancer activity of docetaxel, suggesting its potential application as an adjuvant to existing anticancer chemotherapy. Altogether, our results revealed the complex effect of ML-9 on autophagy and indentified ML-9 as an attractive tool for targeting autophagy in cancer therapy through dual inhibition of both the Akt pathway and the autophagy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP105637501-A	ML-9		105637-50-1	Price

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