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The growth of siRNA-based therapeutics: updated clinical studies.
Abstract More than two decades after the natural gene-silencing mechanism of RNA interference was elucidated, small interfering RNA (siRNA)-based therapeutics have finally broken into the pharmaceutical market. With three agents already approved and many others in advanced stages of the drug development pipeline, siRNA drugs are on their way to becoming a standard modality of pharmacotherapy. The majority of late-stage candidates are indicated for rare or orphan diseases, whose patients have an urgent need for novel and effective therapies. Additionally, there are agents that have the potential to meet the need of...
Source: Biochemical Pharmacology - January 26, 2021 Category: Drugs & Pharmacology Authors: Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong XB Tags: Biochem Pharmacol Source Type: research

Involvement of Pregnane X Receptor in the Impaired Glucose Utilization Induced by Atorvastatin in Hepatocytes.
In conclusion, atorvastatin impaired glucose utilization in hepatocytes via repressing GLUT2 and GCK expressions, which may be partly due to PXR activation. PMID: 26616219 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - November 23, 2015 Category: Drugs & Pharmacology Authors: Ling Z, Shu N, Xu P, Wang F, Zhong Z, Sun B, Li F, Zhang M, Zhao K, Tang X, Wang Z, Zhu L, Liu L, Liu X Tags: Biochem Pharmacol Source Type: research

Estrogen receptor mediates simvastatin-stimulated osteogenic effects in bone marrow mesenchymal stem cells.
In this study, we hypothesize that the estrogen receptor (ER) mediates simvastatin-induced osteogenic differentiation. ER antagonists and siRNA were used to determine the involvement of the ER in simvastatin-induced osteogenesis in mouse bone marrow mesenchymal stem cells (D1 cells). Osteogenesis was evaluated by mRNA expression, protein level/activity of osteogenic markers, and mineralization. The estrogen response element (ERE) promoter activity and the ER-simvastatin binding affinity were examined. Our results showed that the simvastatin-induced osteogenic effects were decreased by treatment with ERα antagonists and ER...
Source: Biochemical Pharmacology - September 24, 2015 Category: Drugs & Pharmacology Authors: Chuang SC, Chen CH, Fu YC, Tai IC, Li CJ, Chang LF, Ho ML, Chang JK Tags: Biochem Pharmacol Source Type: research

Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells.
Abstract The aim of the present study was to explore the signaling pathways associated with the effect of simvastatin on matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia K562 cells. In sharp contrast to its insignificant effect on MMP-2, simvastatin down-regulated MMP-9 protein expression and mRNA levels in K562 cells. Simvastatin-induced Pin1 down-regulation evoked NFκB/p65 degradation. Meanwhile, simvastatin induced JNK-mediated c-Jun and ATF-2 activation. Over-expression of Pin1 suppressed simvastatin-induced MMP-9 down-regulation. Treatment with SP600125 (a JNK inhibitor) or knock-down of...
Source: Biochemical Pharmacology - October 11, 2014 Category: Drugs & Pharmacology Authors: Chen YJ, Chang LS Tags: Biochem Pharmacol Source Type: research