Development of potent small-molecule inhibitors to drug the undruggable steroid receptor coactivator-3 was written by Song, Xianzhou;Chen, Jianwei;Zhao, Mingkun;Zhang, Chengwei;Yu, Yang;Lonard, David M.;Chow, Dar-Chone;Palzkill, Timothy;Xu, Jianming;O’Malley, Bert W.;Wang, Jin. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2016.Product Details of 85692-37-1 This article mentions the following:
Protein-protein interactions (PPIs) play a central role in most biol. processes, and therefore represent an important class of targets for therapeutic development. However, disrupting PPIs using small-mol. inhibitors (SMIs) is challenging and often deemed as “undruggable.”. The authors developed a cell-based functional assay for high-throughput screening to identify SMIs for steroid receptor coactivator-3 (SRC-3 or AIB1), a large and mostly unstructured nuclear protein. Without any SRC-3 structural information, the authors identified SI-2 (I) as a highly promising SMI for SRC-3. SI-2 meets all of the criteria of Lipinski’s rule [Lipinski et al. (2001) Adv Drug Deliv Rev 46(1-3):3-26] for a drug-like mol. and has a half-life of 1 h in a pharmacokinetics study and a reasonable oral availability in mice. As a SRC-3 SMI, SI-2 can selectively reduce the transcriptional activities and the protein concentrations of SRC-3 in cells through direct phys. interactions with SRC-3, and selectively induce breast cancer cell death with IC50 values in the low nanomolar range (3-20 nM), but not affect normal cell viability. Furthermore, SI-2 can significantly inhibit primary tumor growth and reduce SRC-3 protein levels in a breast cancer mouse model. In a toxicol. study, SI-2 caused minimal acute cardiotoxicity based on a hERG channel blocking assay and an unappreciable chronic toxicity to major organs based on histol. analyses. The authors believe that this work could significantly improve breast cancer treatment through the development of “first-in-class” drugs that target oncogenic coactivators. In the experiment, the researchers used many compounds, for example, 1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1Product Details of 85692-37-1).
1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Imidazole has been usedin the lysis, wash and elution buffer for the purification of histidine tagged Sonic Hedgehog(shh-N) protein, in elution buffer in stepwise gradient for the purification of histidine tagged aldo keto reductases using nickel affinity chromatography, as a component of homogenization buffer for the purification of phagosomal compartments from dendritic cells.Product Details of 85692-37-1
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem