95058-81-4sf晶型求助Reference_08_15_2013_091659.pdfVIP

SciFinder® Page 1 1. Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an E3 ubiquitin ligase, particularly targeting the von Hippel-Lindau E3 ubiquitin ligase using hydroxyproline analogs to disrupt the VHL/HIF-1α interaction By Crews, Craig M.; Buckley, Dennis; Ciulli, Alessio; Jorgensen, William; Gareiss, Peter C.; Van Molle, Inge; Gustafson, Jeffrey; Tae, Hyun-Seop; Michel, Julien; Hoyer, Dentin Wade; et al From PCT Int. Appl. (2013), WO 2013106643 A2 Language: English, Database: CAPLUS The invention is related to bifunctional compds., e.g., I, which find utility as modulators of targeted ubiquitination, esp. inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compds. according to the present invention. In particular, the invention is related to compds., which contain on one end a von Hippel-Lindau (VHL) ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degrdn. (and inhibition) of that protein. The invention exhibits a broad range of pharmacol. activities assocd. with the compds. of the invention, consistent with the degrdn./inhibition of targeted polypeptides. Thus, II bound to VHL with a 4.1 µM IC50 value. II was cocrystd. with VHL and shown to bind at the HIF-1α binding site. SciFinder® Page 2 ~0 Citings Copyright © 2013 American Chemical Society (ACS). All Rights Reserved. 2. Tangled Up in Knots: Structures of Inactivated Forms of E. coli Class Ia Ribonucleotide Reductase By Zimanyi, Christina M.; Ando, Nozomi; Brignole, Edward J.; As