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PR-104 showed linear pharmacokinetics, rapid conversion to PR-104A, and evidence of antitumor activity, including partial responses and prolonged stable disease in some patients (282)

In nutrient-rich conditions, mTOR remains active, suppressing autophagy initiation, while under stress conditions such as energy deficiency or DNA damage, the activation of AMP-activated protein kinase (AMPK), p53 or inhibition of pathways like PI3K/Akt and ERK reduces mTOR activity, which then releases the inhibition on autophagy and facilitates its initiation (Yang and Klionsky, 2010)

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