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Sirtuin 2 (SIRT2) is a protein lysine deacylase that has been indicated as a therapeutic target for cancer. To further establish the role of SIRT2 in cancers, it is necessary to develop selective and potent inhibitors. Here, we report the facile synthesis of novel lysine-derived thioureas as mechanism-based SIRT2 inhibitors with anticancer activity. Compounds AF8, AF10, and AF12 selectively inhibited SIRT2 with IC values of 0.06, 0.15, and 0.08 μM, respectively. Compounds AF8 and AF10 demonstrated broad cytotoxicity amongst cancer cell lines, but minimal toxicity in noncancerous cells. AF8 and AF10 inhibited the anchorage-independent growth of human colorectal cancer cell line HCT116 with GI values of ∼7 μM. Furthermore, AF8 potently inhibited tumor growth in a HCT116 xenograft murine model, supporting that SIRT2 is a viable therapeutic target for colorectal cancer.
This article was published in the following journal.
Name: Journal of medicinal chemistry
l-Lysine is a commodity amino acid produced from starch feedstock. Various alternative feedstocks had been used for l-lysine production, but the yield was very low. This study took the first prelimina...
Covalent inhibitors are widely used in drug discovery and chemical biology. Although covalent inhibitors are frequently designed to react with noncatalytic cysteines, many ligand binding sites lack an...
Lysine specific demethylase 1 (LSD1) has emerged as a potential drug target in cancer therapy and a variety of inhibitors have been reported. We have recently reported the discovery of a series of tri...
A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and ...
Thioureas are exquisite building blocks for the construction of five and six membered heterocyclic units, and also display an extensive range of biological activities. 4-Nitro-2-cyano aniline was reac...
The purpose of this study is to establish the parenteral lysine requirements for neonates.
Wheat and wheat derived products are highly consumed around the world. They constitute the major dietary source of protein and energy for many individuals. Wheat contains moderate quantity...
This sub-study aims to assess the effect and breakdown of lysine administration, specifically examining whether it leads to increased plasma 2-AAA in healthy humans.
The purpose of this study is to determine whether incretin-based drugs (used to treat type 2 diabetes) taken either alone in or combination with other anti-diabetic drugs are associated wi...
The purpose of this study is to determine whether incretin-based drugs (used to treat type 2 diabetes) taken either alone or in combination with other anti-diabetic drugs are associated wi...
Prejudice or discrimination based on gender or behavior or attitudes that foster stereotyped social roles based on gender.
A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.
A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...