Chloroquine autophagy inhibition

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  1. isoff Well-Known Member

    Chloroquine autophagy inhibition

    Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.

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    Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the. The antimalarial drug chloroquine CQ disrupts autophagy by inhibiting the acidification of the lysosomes that fuse with the autophagosomes, thereby preventing the degradation of metabolic stress products and inducing apoptosis. Chloroquine-mediated inhibition of autophagy has been demonstrated in melanoma. Tumor cells require autophagy to remove misfolded proteins or damaged cellular organelles. SBI-0206965 was shown to suppress autophagy induced by mTOR inhibition. mTOR signaling is often hyperactive in many tumors and can drive proliferation, so mTOR inhibitors are being investigated as anticancer agents.

    The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead.

    Chloroquine autophagy inhibition

    Inhibition of autophagy with bafilomycin and chloroquine., Inhibition of autophagy with chloroquine is effective in melanoma.

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  5. Autophagy has a pro-tumorigenic role in established tumors and consequently the vast majority of clinical trials focus on autophagy inhibition in cancer. Over the last decade, a dozen Phase I and I/II clinical trials have been completed and published using the autophagy inhibitors, Chloroquine CQ or hydroxychloroquine HCQ in cancer. These.

    • Autophagy inhibition in cancer Clinical Trials Update Novus..
    • Autophagy Inhibitors - Autophagy Sigma-Aldrich.
    • Combination of ERK and autophagy inhibition as a treatment..

    Chloroquine is commonly used to study the role of endosomal acidification in cellular processes 2, 3, such as the signaling of intracellular TLRs. Moreover, Chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation 4. References. 1. Nov 15, 2015 Indeed, preclinical studies have shown that the pharmacological inhibition of autophagy with agents including chloroquine, hydroxychloroquine, metformin, and desmethylclomipramine can enhance the cell-killing effect of cancer therapeutics, and a number of these agents are currently under investigation in clinical trials. However, many of. Chloroquine phosphate 50-63-5 is an antimalarial drug. Inhibits autophagy in a variety of cell lines 1. Induces cell death in breast cancer cell lines and displays antitumor and antimetastatic activity in mouse models of breast cancer 2.

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    COPE Disclosures Plaquenil Toxicity Update Hydroxychloroquine HCQ Background Hydroxychloroquinesulfate •Chloroquine CQ first synthesized in 1930s by Hans Andersag •Alternative to quinine found in Peruvian tree bark •Original use combat malaria in WWII •Less toxic form, hydroxychloroquine HCQ developed later •Started being used in 1950’s, toxicity first noted 1963

    Treatment of hydroxychloroquine overdose - ScienceDirect