Chemical Research Letters, April 2021. Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. 91-10-1, Name is 2,6-Dimethoxyphenol, molecular formula is C8H10O3, COA of Formula: https://www.ambeed.com/products/91-10-1.html, belongs to isothiazole compound, is a common compound. In a patnet, author is Coffey, Kelly, once mentioned the new application about 91-10-1.
Tip60 (KAT5) is a histone acetyltransferase (HAT enzyme) involved in multiple cellular processes including transcriptional regulation, DNA damage repair and cell signalling. In prostate cancer, aggressive cases over-express Tip60 which functions as an androgen receptor co-activator via direct acetylation of lysine residues within the KLKK motif of the receptor hinge region. The purpose of this study was to identify and characterise a Tip60 acetylase inhibitor. High-throughput screening revealed an isothiazole that inhibited both Tip60 and p300 HAT activity. This substance (initially identified as 4-methyl-5-bromoisothiazole) and other isothiazoles were synthesised and assayed against Tip60. Although an authentic sample of 4-methyl-5-bromoisothiazole was inactive against Tip60, in an in vitro HAT assay, 1,2-bis(isothiazol-5-yl)disulfane (NU9056) was identified as a relatively potent inhibitor (IC50 2 mu M). Cellular activity was confirmed by analysis of acetylation of histone and non-histone proteins in a prostate cancer cell line model. NU9056 treatment inhibited cellular proliferation in a panel of prostate cancer cell lines (50% growth inhibition, 8-27 mu M) and induced apoptosis via activation of caspase 3 and caspase 9 in a concentration-and time-dependent manner. Also, decreased androgen receptor, prostate specific antigen, p53 and p21 protein levels were demonstrated in response to treatment with NU9056. Furthermore, pre-treatment with NU9056 inhibited both ATM phosphorylation and Tip60 stabilization in response to ionising radiation. Based on the activity of NU9056 and the specificity of the compound towards Tip60 relative to other HAT enzymes, these chemical biology studies have identified Tip60 as a potential therapeutic target for the treatment of prostate cancer.
One of the oldest and most widely used commercial enzyme inhibitors is aspirin, which selectively inhibits one of the enzymes involved in the synthesis of molecules that trigger inflammation. Interested yet? Keep reading other articles of 91-10-1, you can contact me at any time and look forward to more communication. COA of Formula: https://www.ambeed.com/products/91-10-1.html.
Reference:
Isothiazole – Wikipedia,
,Isothiazole – ScienceDirect.com