IMT1B

• CAT Number: I044686
• CAS Number: 2304621-06-3
• Molecular Formula: C24H21ClFNO6
• Molecular Weight: 473.88
• Purity: ≥95%
• Synonyms: (3S)-1-[(2R)-2-[4-(2-chloro-4-fluorophenyl)-2-oxochromen-7-yl]oxypropanoyl]piperidine-3-carboxylic acid
• InChI: InChI=1S/C24H21ClFNO6/c1-13(23(29)27-8-2-3-14(12-27)24(30)31)32-16-5-7-18-19(11-22(28)33-21(18)10-16)17-6-4-15(26)9-20(17)25/h4-7,9-11,13-14H,2-3,8,12H2,1H3,(H,30,31)/t13-,14+/m1/s1
• InChIKey: PFEKWBKJUBCXDT-KGLIPLIRSA-N
• SMILES: CC(C(=O)N1CCCC(C1)C(=O)O)OC2=CC3=C(C=C2)C(=CC(=O)O3)C4=C(C=C(C=C4)F)Cl

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].

Reference

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