7SLV

Vanin-1 complexed with Compound 3

7SLV の概要

• エントリーDOI: 10.2210/pdb7slv/pdb
• 分子名称: Pantetheinase, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-6)-[beta-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: pantetheine, sbdd, pyrimdine carboxamide, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56605.59

構造登録者

Vajdos, F.F. (登録日: 2021-10-25, 公開日: 2022-01-12, 最終更新日: 2024-10-30)

主引用文献

Casimiro-Garcia, A.,Allais, C.,Brennan, A.,Choi, C.,Dower, G.,Farley, K.A.,Fleming, M.,Flick, A.,Frisbie, R.K.,Hall, J.,Hepworth, D.,Jones, H.,Knafels, J.D.,Kortum, S.,Lovering, F.E.,Mathias, J.P.,Mohan, S.,Morgan, P.M.,Parng, C.,Parris, K.,Pullen, N.,Schlerman, F.,Stansfield, J.,Strohbach, J.W.,Vajdos, F.F.,Vincent, F.,Wang, H.,Wang, X.,Webster, R.,Wright, S.W.
Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1.
J.Med.Chem., 65:757-784, 2022

PubMed Abstract: A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, was identified with a suitable profile for advancement into preclinical development.

PubMed: 34967602
DOI: 10.1021/acs.jmedchem.1c01849

実験手法

X-RAY DIFFRACTION (2.13 Å)