Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel–Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible …
LP Vu, CJ Diehl, R Casement, AG Bond… - Journal of Medicinal …, 2023 - ACS Publications
Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation
to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the
ubiquitin E3 ligase von Hippel–Lindau (VHL). Here, we performed a structure-guided and
bioactivity-driven design of new VHL inhibitors. Our iterative and combinatorial strategy
focused on chemical variability at the phenylene unit and encompassed further points of
diversity. The exploitation of tailored phenylene fragments and the stereoselective …
to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the
ubiquitin E3 ligase von Hippel–Lindau (VHL). Here, we performed a structure-guided and
bioactivity-driven design of new VHL inhibitors. Our iterative and combinatorial strategy
focused on chemical variability at the phenylene unit and encompassed further points of
diversity. The exploitation of tailored phenylene fragments and the stereoselective …
Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia …
LP Vu, C Diehl, R Casement, A Bond, C Steinebach… - 2023 - chemrxiv.org
Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation
to hypoxia in humans. HIF-1α protein level and activity is tightly regulated by the ubiquitin E3
ligase von Hippel-Lindau (VHL). Here, we performed a structure-guided and bioactivity-
driven design of new VHL inhibitors. Our iterative and combinatorial strategy focused on
chemical variability at the phenylene unit and encompassed further points of diversity. The
exploitation of tailored phenylene fragments and the stereoselective installation of the …
to hypoxia in humans. HIF-1α protein level and activity is tightly regulated by the ubiquitin E3
ligase von Hippel-Lindau (VHL). Here, we performed a structure-guided and bioactivity-
driven design of new VHL inhibitors. Our iterative and combinatorial strategy focused on
chemical variability at the phenylene unit and encompassed further points of diversity. The
exploitation of tailored phenylene fragments and the stereoselective installation of the …