126992-69-6Relevant academic research and scientific papers
INHIBITORS OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) AND METHODS OF USE THEREOF
-
Paragraph 00309; 00311-00314, (2021/08/13)
Compounds and methods for their preparation and use as therapeutic or prophylactic agents, for example for treatment of cancer, bacterial or viral diseases by targeting Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1).
PCSK9-INHIBITING COMPOUNDS
-
Page/Page column 39-40, (2021/11/26)
The invention relates to compounds of general formula (I): having inhibitory activity against the PCSK9 enzyme. Said compounds can be used, for example, in the prevention and/or treatment of dyslipidaemia.
METHODS AND COMPOUNDS FOR TREATING DISORDERS
-
Page/Page column 145-146, (2019/08/26)
The present invention relates to methods and compositions for the treatment of BAF-related disorders such as cancers and viral infections.
Computationally Driven Structure Optimization, Synthesis, and Biological Evaluation of Imidazole-Based Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Inhibitors
Lammi, Carmen,Sgrignani, Jacopo,Arnoldi, Anna,Lesma, Giordano,Spatti, Claudia,Silvani, Alessandra,Grazioso, Giovanni
supporting information, p. 6163 - 6174 (2019/08/02)
Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of the hepatic low-density lipoprotein receptor (LDLR), which in turn regulates the circulating low-density lipoprotein cholesterol (LDL-C) level. For this reason, the PCSK9 inhibition, by small molecules or peptides, is a validated therapeutic approach for fighting hypercholesterolemia and cardiovascular diseases. In this field, we have recently reported an imidazole-based peptidomimetic that has shown PCSK9 inhibitory activity in the micromolar range. Here, by applying advanced computational techniques, the binding mechanism of that imidazole peptidomimetic was predicted. Then, among a small set of poly-imidazole analogs, compounds showing the highest theoretical affinity were suitably synthesized, relying on a van Leusen reaction based multicomponent strategy. One compound (named RIm13) displayed a PCSK9 inhibitory activity 10-fold lower than the template compound, and, remarkably, at a concentration of 1 μM, it successfully prevented the LDLR degradation mediated by PCSK9 on HepG2 cells. As well as increasing the LDL uptake at the same concentration, RIm13 represents currently one of the most potent small molecules targeting the PCSK9/LDLR protein-protein interaction.
