25126-45-8

Upstream product

• 2389-60-8 Z-Lys(Boc)-OH 
• 62-53-3 aniline 

Downstream Products

• 25126-04-9 (S)-5-(benzyloxycarbonylamino)-6-oxo-6-(phenylamino)hexan-1-aminium chloride 
• 790999-53-0 5-tert-butoxycarbonylamino-1-phenylcarbamoylpentylamine 
• 1125842-09-2 benzyl (S)-(6-ethanethioamido-1-oxo-1-(phenylamino)hexan-2-yl)carbamate 

Relevant academic research and scientific papers

Novel Lysine-Based Thioureas as Mechanism-Based Inhibitors of Sirtuin 2 (SIRT2) with Anticancer Activity in a Colorectal Cancer Murine Model

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

Novel Lysine-Based Thioureas as Mechanism-Based Inhibitors of Sirtuin 2 (SIRT2) with Anticancer Activity in a Colorectal Cancer Murine Model

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

Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2

Sirtuins catalyze the NAD+ dependent deacetylation of N ε-acetyl lysine residues to nicotinamide, O′-acetyl-ADP- ribose (OAADPR) and Nε-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel Nε-modified lysine containing inhibitors against SIRT1 and SIRT2. Nε-Selenoacetyl and N ε-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied Nε-thioacetyl group. The Nε-3,3-dimethylacryl and Nε-isovaleryl moieties gave significant inhibition in comparison to the Nε-acetyl group present in the substrates. In addition, the studied Nε- alkanoyl, Nε-α,β-unsaturated carbonyl and N ε-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the Nε-modification. These results are applicable for further screening of Nε-acetyl analogues.

Inhibition of human sirtuins by in situ generation of an acetylated lysine-ADP-ribose conjugate

A new type of small-molecular slrtuln Inhibitor was designed on the basis of the proposed catalytic mechanism for deacetylatlon of acetylated lysine substrates by sirtuins. Among the compounds thus designed and synthesized, we found that 2k, which contains an ethoxycarbonyl group at the a position to the acetamlde of acetylated lysine substrate analogue 1, showed potent Inhibitory activity In an In vitro assay using recombinant SIRT1, with high selectivity over SIRT2 and SIRT3. Mechanistic study by means of kinetic analysis, mass spectroscopy, and computation Indicated that the enol form of compound 2k nucleophlllcally attacks NAD+ In the active site of SIRTs to afford the stable compound 2k-ADP-rlbose conjugate 5, leading to Inhibition of the enzyme activity. Compound 2k also caused a dose-dependent Increase of p53 acetylatlon In human colon cancer HCT116 cells, Indicating Inhibition of SIRT1 In the cells. These results have Implications for the development of selective slrtuln Inhibitors by means of mechanismbased drug design.

Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine

To identify cell-active sirtuin inhibitors containing N-thioacetyl lysine, we synthesized compound 1, which was designed based on the structure of the reported N-ethoxycarbonylacetyl lysine-based sirtuin inhibitor NCS-12k. Compound 1 selectively inhibited

SIRTUIN INHIBITORS

This invention relates to compounds and methods for the inhibition of sirtuin enzymatic activity. More particularly, the invention provides for compounds of formula (I), Y__L__Z__D, and N-oxides, hydrates, solvates, pharma