IndraLab

Statements

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"Aside from DC661, HCQ and Lys05 can also inhibit PPT1 (Rebecca et al., 2019)."
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"Chloroquine and hydroxychloroquine were shown to inhibit PPT1 activity in neuroblastoma cancer cell lines, with an IC of 47.2 μM for chloroquine and IC of 109.1 μM for hydroxychloroquine; however, they did not show significant changes in the ΔT (Figure 3D)."
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"We and others have shown that HCQ, GNS561, and DC661 bind to and inhibit the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1), and PPT1 KO recapitulates the phenotype of these inhibitors (5,6,11)."
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"PPT1 inhibition by HCQ- or DC661-treated M2 macrophages produced a significant increase in secreted IFN-β secretion compared with vehicle control (Figure 6B)."
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"Similar data were obtained in melanoma models , where inhibition of palmitoyl-protein thioesterase 1 by hydroxychloroquine synergized with anti-PD1 therapy to impair tumour growth and improve survival in mice155 ."
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"HDSF may also exert effects by mediating the activation of the same immunosuppressive pathway as that mediated by HCQ, which also inhibits PPT1 ."
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"Interestingly, PPT1 inhibition by HCQ or DC661 also led to an increased effect of anti-PD-1 therapy in melanoma in vitro and in a murine in vivo model [133], echoing findings recently made in pancreatic cancer [50]."
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"Interestingly , HCQ was introduced by other study to inhibit PPT1 activity 24 ."
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"While the combination of anti–PD-1 and PPT1 inhibition by HCQ did not result in significant change in the number of activated T cells as assessed by immunophenotyping, the clear changes in macrophage populations could also have a significant impact on antitumor activity."
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"HCQ and Lys05 also bound to and inhibited PPT1 activity, but only DC661 maintained activity in acidic media."
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"PPT1 has been found to be upregulated in RA synovial tissue and is inhibited by HCQ in vitro ( Rebecca et al ., 2019 ) ."
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