2743336-70-9

mHTT-IN-2 (compound 27) is a potent inhibitor (EC50=0.066 μM) of mutant huntingtin (mHTT). mHTT-IN-2 reduces canonical splicing of HTT RNA exons [49-50] and is a splicing regulator of the huntingtin (HTT) gene. mHTT-IN-2 exhibits inhibitory activity in vitro and in vivo in human HD stem cells and mouse BACHD models. mHTT-IN-2 may be used in the study of branaplam-related peripheral neuropathy[1].

[1] Liu L, et al. Identification and Optimization of RNA-Splicing Modulators as Huntingtin Protein-Lowering Agents for the Treatment of Huntington's Disease. J Med Chem. 2023 Sep 15.. . DOI:10.1021/acs.jmedchem.3c01173