IMT1B (LDC203974) is an orally active, noncompetitive, and specific allosteric inhibitor of mitochondrial RNA polymerase (POLRMT), leading to the inhibition of mitochondrial DNA (mtDNA) expression. IMT1B exhibits anti-tumor effects [1].
体内研究
IMT1B (100 mg/kg; p.o.; daily; for four weeks) induces a significant reduction in tumor size in mice bearing xenografts [1].
IMT1B decreases mtDNA transcript levels and levels of respiratory-chain subunits in tumors [1].
IMT1B demonstrates favorable oral bioavailability (101%) and Cmax (5149 ng/mL) upon oral administration (10 mg/kg) in mice [1].
IMT1B demonstrates an elimination half-life (1.88 h) attributed to plasma clearance (0.44 L/h/kg) following intravenous administration (1 mg/kg) in mice [1].
体外研究
IMT1B is a noncompetitive inhibitor inducing a conformational change in POLRMT, thereby impeding substrate binding and transcription in a dose-dependent manner in vitro[1].
IMT1B (0.01 nM-10 μM; 72-168 hours) exhibits a dose-dependent reduction in cell viability in A2780, A549, and HeLa cells [1].
IMT1B leads to depletion of cellular metabolites [1].
IMT1B elevates the levels of mono- and diphosphate nucleotides, leading to a significant increase in the AMP/ATP ratio and phosphorylated AMPK levels [1].
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