64985-42-8Relevant articles and documents
Insulin Analogues with Altered Insulin Receptor Isoform Binding Specificities and Enhanced Aggregation Stabilities
Chrudinova, Martina,Halamova, Tereza,Jiracek, Jiri,Kurochka, Andrii,Mitrova, Katarina,Mrzilkova, Karolina,Panikova, Terezie,Picha, Jan,Selicharova, Irena,Zakova, Lenka
supporting information, p. 14848 - 14859 (2021/10/20)
Insulin is a lifesaver for millions of diabetic patients. There is a need for new insulin analogues with more physiological profiles and analogues that will be thermally more stable than human insulin. Here, we describe the chemical engineering of 48 insulin analogues that were designed to have changed binding specificities toward isoforms A and B of the insulin receptor (IR-A and IR-B). We systematically modified insulin at the C-terminus of the B-chain, at the N-terminus of the A-chain, and at A14 and A18 positions. We discovered an insulin analogue that has Cα-carboxyamidated Glu at B31 and Ala at B29 and that has a more than 3-fold-enhanced binding specificity in favor of the "metabolic"IR-B isoform. The analogue is more resistant to the formation of insulin fibrils at 37 °C and is also more efficient in mice than human insulin. Therefore, [AlaB29,GluB31,amideB31]-insulin may be interesting for further clinical evaluation.
Synthesis of jacaranone-derived nitrogenous cyclohexadienones and their antiproliferative and antiprotozoal activities
Presser, Armin,Lainer, Gunda,Kretschmer, Nadine,Schuehly, Wolfgang,Saf, Robert,Kaiser, Marcel,Kalt, Marc-Manuel
, (2018/11/23)
The cytotoxic and antiprotozoal activities of the phytoquinoide, jacaranone, and related compounds have been an ongoing topic in recent drug discovery. Starting from the natural product-derived cyclohexadienone scaffold, a series of nitrogen-containing derivatives were synthesized and subsequently evaluated for their antiproliferative and antiprotozoal activity. Anticancer potency was analyzed using different types of cancer cell lines: MDA-MB-231 breast cancer, CCRF-CEM leukemia, HCT-116 colon cancer, U251 glioblastoma, and, in addition, non-tumorigenic MRC-5 lung fibroblasts. Antiproliferative activities at micromolar concentrations could be shown. Antiprotozoal activity was assessed against Plasmodium falciparum NF54 and Trypanosoma brucei rhodesiense STIB900. For all compounds, selectivity indices (SI) were calculated based on assessed cytotoxicity towards L6 cells. In addition, the structure-activity-relationships and physicochemical parameters of these compounds are discussed.
Ezrin inhibitors and methods of making and using
-
, (2017/01/05)
The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.