Targeting the von Hippel-Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction was written by Buckley, Dennis L.;Van Molle, Inge;Gareiss, Peter C.;Tae, Hyun Seop;Michel, Julien;Noblin, Devin J.;Jorgensen, William L.;Ciulli, Alessio;Crews, Craig M.. And the article was included in Journal of the American Chemical Society in 2012.Product Details of 19668-85-0 This article mentions the following:
E3 ubiquitin ligases, which bind protein targets, leading to their ubiquitination and subsequent degradation, are attractive drug targets due to their exquisite substrate specificity. However, the development of small-mol. inhibitors has proven extraordinarily challenging as modulation of E3 ligase activities requires the targeting of protein-protein interactions. Using rational design, we have generated the first small mol. targeting the von Hippel-Lindau protein (VHL), the substrate recognition subunit of an E3 ligase, and an important target in cancer, chronic anemia, and ischemia. We have also obtained the crystal structure of VHL bound to our most potent inhibitor, confirming that the compound mimics the binding mode of the transcription factor HIF-1α, a substrate of VHL. These results have the potential to guide future development of improved lead compounds as therapeutics for the treatment of chronic anemia and ischemia. In the experiment, the researchers used many compounds, for example, 3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0Product Details of 19668-85-0).
3-Methylisoxazole-5-acetic Acid (cas: 19668-85-0) belongs to isoxazole derivatives. Isoxazole rings are found in some natural products, such as ibotenic acid and muscimol. Some alternative routes for the synthesis of isoxazoles have also been developed and reported. The 2-benzoyl-2-halo-2H-azirines provide 4-haloisoxazoles in good yields after heating in toluene at reflux temperature.Product Details of 19668-85-0
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem