1126-81-4Relevant articles and documents
PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity
Benincasa, Monica,Zahariev, Sotir,Pelillo, Chiara,Milan, Annalisa,Gennaro, Renato,Scocchi, Marco
, p. 210 - 219 (2015)
The proline-rich antibacterial peptide Bac7(1-35) protects mice against Salmonella typhimurium infection, despite its rapid clearance. To overcome this problem the peptide was linked to a polyethylene glycol (PEG) molecule either via a cleavable ester bond or via a non-hydrolysable amide bond. Both the PEGylated conjugates retained most of the in vitro activity against S. typhimurium. In addition, the ester bond was cleaved in human serum or plasma, releasing a carboxymethyl derivative of Bac7(1-35) which accounts for a higher activity of this peptide with relative to the other, non-hydrolysable form. Both PEGylated peptides maintained the capacity of the unconjugated form to kill bacteria without permeabilizing the bacterial membranes, by penetrating into cells. They exploited the same transporter as unmodified Bac7(1-35), suggesting it has the capacity to internalize quite sizeable cargo if this is linked to Bac7 fragment. PEGylation allows the peptide to have a wide distribution in mice, and a slow renal clearance, indicating that this strategy would improve the bioavailability of Bac7, and in principle of other antimicrobial peptides. This can be an equally important issue to reducing cytotoxicity for therapeutic use of these antibacterials.
Tozasertib Analogues as Inhibitors of Necroptotic Cell Death
Hofmans, Sam,Devisscher, Lars,Martens, Sofie,Van Rompaey, Dries,Goossens, Kenneth,Divert, Tatyana,Nerinckx, Wim,Takahashi, Nozomi,De Winter, Hans,Van Der Veken, Pieter,Goossens, Vera,Vandenabeele, Peter,Augustyns, Koen
, p. 1895 - 1920 (2018/03/21)
Receptor interacting protein kinase 1 (RIPK1) plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, suggesting that this pathway might be druggable. Most inhibitors of RIPK1 are classified as either type II or type III kinase inhibitors. This opened up some interesting perspectives for the discovery of novel inhibitors that target the active site of RIPK1. Tozasertib, a type I pan-aurora kinase (AurK) inhibitor, was found to show a very high affinity for RIPK1. Because tozasertib presents the typical structural elements of a type I kinase inhibitor, the development of structural analogues of tozasertib is a good starting point for identifying novel type I RIPK1 inhibitors. In this paper, we identified interesting inhibitors of mTNF-induced necroptosis with no significant effect on AurK A and B, resulting in no nuclear abnormalities as is the case for tozasertib. Compounds 71 and 72 outperformed tozasertib in an in vivo TNF-induced systemic inflammatory response syndrome (SIRS) mouse model.
Glucokinase activating agent containing halogenated quinoline structure, preparation method and application thereof
-
Paragraph 0038; 0041-0042, (2017/08/29)
The invention relates to the field of medicines related to II-type diabetes, particularly relates to a glucokinase activating agent containing a halogenated quinoline structure, a preparation method and an application thereof in preparation of II-type diabetes medicines. The structure formula is shown in the specification, wherein, X is selected from a halogen substituent group.
