huntingtin

Buntanetap ((+)-Phenserine) 是一种具有口服活性的多神经毒性蛋白（TINAPs）抑制剂，可用于研究神经系统疾病、内分泌与代谢疾病和心血管疾病。

Votoplam HCl(沃妥扑兰盐酸盐)是Votoplam的盐酸盐形式。Votoplam是一种全身作用的基因剪接调节剂，能够下调亨廷顿蛋白(huntingtin protein)的水平，主要用于抑制亨廷顿病(HD)。

mHTT-IN-2（化合物27）作为mHTT的一种有效抑制剂，具有EC50值为0.066 μM，能够降低HTT RNA外显子[49-50]的规范剪接，从而调节HTT基因的剪接。在人类HD干细胞和BACHD小鼠模型上，mHTT-IN-2已显示出明显的体外及体内活性。此外，该化合物也被应用于研究与branaplam相关的周围神经病变。

Polyglutamine binding peptide 1 (QBP1) 是一种专用于抑制聚谷氨酰胺 (polyQ) 的肽类抑制剂。它能够在体外条件下阻止 polyQ 蛋白的聚集，并在细胞培养实验中抑制由 polyQ 引发的细胞凋亡。

16F16 is a protein disulfide isomerase (PDI) inhibitor.1It inhibits PDI reductase activity in an enzyme assay when used at concentrations ranging from 1 to 100 μg/ml.116F16 reduces PC12 cell apoptosis induced by the misfolded huntingtin protein HTTQ103. It suppresses PDI-dependent mitochondrial outer membrane permeabilization (MOMP) in isolated PC12 cell mitochondria. 16F16 (2, 3, 4, and 10 μM) reduces HTTN90Q73mutant huntingtin-induced medium spinal neuron death and MOMP in rat corticostriatal slices. It also reduces pyramidal neuron death induced by amyloid-β precursor protein (APP) in rat corticostriatal slices. 1.Hoffstrom, B.G., Kaplan, A., Letso, R., et al.Inhibitors of protein disulfide isomerase suppress apoptosis induced by misfolded proteinsNat. Chem. Biol.6(12)900-906(2010)

Chloroguanabenz is an antiprion agent and a derivative of the α2-adrenergic receptor agonist guanabenz . It inhibits prion formation in yeast and mammalian cell-based assays. Chloroguanabenz reduces the levels of both soluble and aggregated forms of the truncated Huntingtin derivative Htt48 in an HEK293T cellular model of Huntington's disease.

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.

Meclocycline is a tetracycline antibiotic with broad antimicrobial activity. Meclocycline inhibits lactate dehydrogenase (LDH) release and cell toxicity induced by expression of htt-N63-148Q, a mutant form of the huntingtin gene, without altering htt-N63-148Q protein levels in PC12 cells.

mHTT-IN-1 (Example 1) 为针对突变亨廷顿蛋白 (mHTT) 的高效抑制剂，该蛋白具毒性，主导遗传性常染色体显性神经退行性疾病—亨廷顿氏病 (HD) 的发生。mHTT-IN-1 能有效降低 mHTT 水平，其 EC50 值为 0.46 nM。

LC3-mHTT-IN-AN1 是一种 mHTT-LC3 接头化合物，可与突变亨廷顿蛋白 (mHTT) 和 LC3B 相互作用。 它将 mHTT 靶向自噬体以等位基因选择性方式降低培养的亨廷顿病小鼠神经元中的 mHTT 水平。

XIE62-1004 是一种促进p62与LC3相互作用的诱导剂。通过与p62的ZZ域结合，导致p62自我聚集并与自噬体膜上的LC3相互作用；促进货物蛋白被送往自噬体以便降解。在体外及体内以浓度依赖和时间依赖的方式活性，并特异性针对野生型p62。在体外诱导突变型huntingtin的降解。也可以用于AUTAC蛋白质降解系统，通过p62自我聚集及与LC3的相互作用来诱导自噬。

Onjisaponin B 是从远志中提取的一种天然产物，可通过 AMPK-mTOR 信号通路诱导自噬，提高 NGF 水平并加速突变型亨廷顿蛋白和 A53T α±-突触核蛋白的清除，可研究帕金森病和亨廷顿病。