An antisense oligonucleotide (ASO) is a single-strand DNA sequence complementary to a desired messenger RNA (mRNA) sequence. Antisense therapy targets gene sequences using antisense oligonucleotides by binding the ASO to the mRNA strand. This creates an inhibitory complex that reduces plasma protein levels by preventing translation.<unk>  is a second-generation phosphorothioate antisense oligonucleotide. Phosphorothioates are oligonucleotides with a sulfur ion replacing an oxygen molecule in the chain. They have high antisense activity due to their increased chirality, nuclease stability, and solubility. Second-generation oligonucleotides are highly specific to the target mRNA sequence, increasing the affinity of the compound.<unk>  acts as an anti-cancer drug by binding to the mRNA initiation site of the clusterin gene, reducing clusterin protein plasma concentrations. The synthetic addition of a 2’-methocyethyl on each nucleotide bookending the phosphorothioate backbone causes: * An increased affinity for the RNA54 targeted gene sequence * An increased resistance to digestive nucleases * Decreased toxicity * Increased tissue half-life by approximately seven days * Decrease adverse side effects, enabling more potent concentrations Clusterin is upregulation in many tumours including prostate, breast, non-small cell lung, ovary and colorectal. It has been linked with the development of aggressive tumours by protecting the cells from apoptosis. It is also upregulated in response to standard cancer treatments including chemotherapy, androgen deprivation therapy, and radiation therapy. This resistance is caused by the inhibition of the pro-apoptotic BLC2 gene, prevention of protein aggregation, and increased NF-KB. The anti-apoptotic activity of clusterin in aiding tumour growth is due to interactions with protein complexes. These include: * The binding of clusterin to a structurally altered Ku70–Bax complex * Regulation of Nuclear Factor (NF)-κB activity and signalling * Kinase ERK and AKT Kinase * Promoted epithelial-mesenchymal transition
Custirsen
Truenat
Epiestriol
Bolesatine
Sesquimustard
Esthiomene
Phenibut
Penmesterol