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IMT1

CAS No. : 2304621-31-4

MCE 国际站：IMT1

产品活性：IMT1 是首创的，特异性和非竞争性的人类线粒体 RNA 聚合酶 (POLRMT) 抑制剂。IMT1 引起 POLRMT 的构象变化，从而在体外以剂量依赖性方式阻断底物结合和转录。IMT1 降低了脱氧核苷三磷酸水平和柠檬酸循环中间体，导致细胞氨基酸水平显着消耗。IMT1 有潜力用于线粒体转录等相关疾病的研究。

研究领域：Metabolic Enzyme/Protease  |  Cell Cycle/DNA Damage

作用靶点：Mitochondrial Metabolism  |  DNA/RNA Synthesis

In Vitro: IMT1 (0.00001-10 μM; 0-168 h) has a dose-dependent decrease in cell viability in A2780, A549 and HeLa cells. IMT1 shows a strong decrease in cell viability in about one third of the cancer cell lines, 89 cancer cell lines and primary cells (IMR90 lung fibroblasts and human peripheral blood mononuclear cells (PBMCs)), whereas primary cells remained unresponsive.
IMT1 (0.01-10 μM; for 24-200 h) causes a dose-dependent decrease in the levels of mitochondrial transcripts and gradual depletion of mtDNA in HeLa cells. There is a dose-dependent decrease in the levels of subunits (NDUFB8, UQCRC2 and COXI) of respiratory chain complexes I, III and IV.
IMT1 reveals a time-dependent and marked increase in the levels of mono- and diphosphate nucleotides that results in a considerable increase in the AMP/ATP ratio and levels of phosphorylated AMPK in A2780 cells.
IMT1 severely impairs mtDNA gene expression in A2780 cells that express wild-type POLRMT, whereas cells that express mutant POLRMT (L796Q or L816Q) are resistant.
POLRMT is essential for mtDNA transcription and biogenesis of the oxidative phosphorylation (OXPHOS) system.

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