IMT1B (C09-1140-541)

IMT1B (LDC203974) is an orally active, noncompetitive and specific allosteric inhibitor of mitochondrial RNA polymerase (POLRMT) and inhibits mitochondrial DNA (mtDNA) expression. IMT1B has anti-tumour effectsIn VitroIMT1B is a noncompetitive inhibitor that causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro. ?/nIMT1B (0.01 nM-10 μM; 72-168 hours) dose-dependently decreases in cell viability in A2780, A549 and HeLa cells. ?/nIMT1B depletes cellular metabolites. ?/nIMT1B increases the levels of mono- and diphosphate nucleotides that results in a considerable increase in the AMP/ATP ratio and levels of phosphorylated AMPK. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: A2780 cells Concentration: 0.01 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM Incubation Time: 72 hours, 96 hours, 168 hours Result: Decreased cell viability in a dose-dependent manner.In VivoIMT1B (100 mg/kg; p.o.; daily; for four weeks) significantly reduces tumour size in mice containing xenografts . ?/nIMT1B reduces mtDNA transcript levels and respiratory-chain subunit levels in tumours . ?/nIMT1B exhibits good oral bioavailability (mice 101 %) and C max (mice 5149 ng/mL) following oral administration (mice 10 mg/kg) . ?/nIMT1B exhibits elimination half-life (mice 1.88 h) due to plasma clearance (mice 0.44 L/h/kg) following intravenous administration (mice 1 mg/kg) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 7-9 weeks female BALB/c nude mice, with A2780 cells xenograft Dosage: 100 mg/kg Administration: Oral administration, daily, for four weeks Result: Led to a clear reduction of tumour volume. Animal Model: Mice Dosage: 1 mg/kg for i.v.; 10 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous administration and oral administration Result: Oral bioavailability (101%), C max (5149 ng/mL), T 1/2 (1.88 h).IC50& Target:POLRMT. Specification: 10mM in DMSO Molecular Formula: C24H21ClFNO6 Molecular Weight: 473.88