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Overview
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Background
CRT5 is a novel and specific PKD inhibitor [1]. PKDs (Protein kinase Ds) are DAG (diacylglycerol)-stimulated serine/threonine protein kinases [1]. Three known PKD isoforms have been identified: PKD1–PKD3. PKD acted as an mediator implicated in diverse cellular functions, including proliferation, cellular trafficking, survival and regulation of transcription [1].In vitro: The non-linear regression analysis revealed that LD50 value of CRT5 was 17 μM. The biochemical IC50 value of CRT5 for PKD1, PKD2 and PKD3 were 1, 2 and 1.5 nM, respectively [1]. CRT5 (1 μM) completely inhibited PKD1 and PKD2, but showed little inhibitory effect on the PKC isoforms. CRT5 significantly reduced VEGF-induced phosphorylation of HSP27 at the position Ser82. CRT5 significantly reduced the migratory response towards VEGF by 42–51%. CRT5 decreased the proliferation of control cells not treated with VEGF to a less extent. VEGF increased HUVEC tubule formation in a collagen-based assay. CRT5 markedly inhibited VEGF-induced tubulogenesis [1].
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