Huntingtin Inhibitor

Desonide is a non-fluorinated corticosteroid anti-inflammatory agent that acts on the glucocorticoid receptor. Desonide can also specifically bind to the mutant huntingtin protein (mHTT), reducing the level and toxicity of mHTT. Desonide can be used in the research of Huntington's disease and inflammatory diseases such as atopic dermatitis.

SEN177 is an orally effect glutamine cyclase (QC) inhibitor. The K_i of SEN177 for human glutamine cyclase (hQC) is 20 nM, and the IC₅₀ is 13 nM. SEN177 interferes with the interaction between CD47 and SIRRPα, and has anti-tumor activity. SEN177 reduces aggregation and apoptosis caused by HTT mutation in Huntington model, and can be used in the study of neurodegenerative diseases.

Brezosiran is a siRNA that inhibits huntingtin synthesis.

Brezosiran sodium is a siRNA that inhibits huntingtin synthesis.

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.

C2-8 is an inhibitor of polyglutamine (polyQ) aggregation (IC₅₀s=25 and 0.05 μM for recombinant HDQ51 and in PC12 cells, respectively). It also inhibits polyQ aggregation in organotypic hippocampal slice cultures isolated from R6/2 transgenic mice and reduces neurodegeneration in a dose-dependent manner in a Drosophila model of Huntington's disease. C2-8 (100 and 200 mg/kg) reduces huntingtin aggregate size, reduces neuronal atrophy, and improves motor performance in a rotarod test in the R6/2 transgenic mouse model of Huntington's disease.

FITC-labeled Tominersen (sodium) is the Tominersen labeled with FITC. Tominersen (RG6042) is a second-generation 2′-O-(2-methoxyethyl) antisense oligonucleotide that targets huntingtin protein (HTT) mRNA and potently suppresses HTT production. Tominersen improves survival and reduces brain atrophy in mice. Tominersen can be used for the research of Huntington’s disease (HD).

Polyglutamine binding peptide 1 (QBP1) is a peptide inhibitor of polyglutamine (polyQ). Polyglutamine binding peptide 1 inhibits polyQ protein aggregation in vitro and suppresses polyQ-induced cell death in cell culture.

mHTT-IN-1 (Example 1) is a potent mutant huntingtin (mHTT) inhibitor. mHTT is toxic and a major cause of the inherited autosomal dominant neurodegenerative disorder, Huntington's disease (HD). mHTT-IN-1 conducts the reduction of mHTT with an EC₅₀ value of 46 nM.