IMT1B (LDC203974) 是一种具有口服活性的，非竞争性的，特异性的线粒体 RNA 聚合酶 (POLRMT) 别构抑制剂，可抑制线粒体 DNA (mtDNA) 的表达。IMT1B 具有抗肿瘤作用。
货号:ajcx33738
CAS:2304621-06-3
分子式:C24H21ClFNO6
分子量：473.88
溶解度:DMSO : 250 mg/mL (527.56 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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 effects[1].

IMT1B is a noncompetitive inhibitor that causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro[1].IMT1B (0.01 nM-10 μM; 72-168 hours) dose-dependently decreases in cell viability in A2780, A549 and HeLa cells[1].IMT1B depletes cellular metabolites[1].IMT1B increases the levels of mono- and diphosphate nucleotides that results in a considerable increase in the AMP/ATP ratio and levels of phosphorylated AMPK[1].

IMT1B (100 mg/kg; p.o.; daily; for four weeks) significantly reduces tumour size in mice containing xenografts[1].IMT1B reduces mtDNA transcript levels and respiratory-chain subunit levels in tumours[1].IMT1B exhibits good oral bioavailability (mice 101 %) and Cmax (mice 5149 ng/mL) following oral administration (mice 10 mg/kg)[1].IMT1B 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)[1].

[1]. Nina A Bonekamp, et al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature. 2020 Dec;588(7839):712-716.