7A13

CRYSTAL STRUCTURE OF HUMAN METHIONINE AMINOPEPTIDASE-2 IN COMPLEX WITH AN INHIBITOR GSK1978537A (COMPOUND 27)

7A13 の概要

• エントリーDOI: 10.2210/pdb7a13/pdb
• 分子名称: Methionine aminopeptidase 2, PHOSPHATE ION, 5-chloranyl-3-(3-methoxyphenyl)-1~{H}-indole-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: methionine aminopeptidase-2, 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: 42585.55

構造登録者

Thorpe, J.H. (登録日: 2020-08-11, 公開日: 2020-09-23, 最終更新日: 2024-10-09)

主引用文献

Hirst, D.J.,Brandt, M.,Bruton, G.,Christodoulou, E.,Cutler, L.,Deeks, N.,Goodacre, J.D.,Jack, T.,Lindon, M.,Miah, A.,Page, K.,Parr, N.,Shukla, L.,Sims, M.,Thomas, P.,Thorpe, J.,Holmes, D.S.
Structure-based optimisation of orally active & reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'.
Bioorg.Med.Chem.Lett., 30:127533-127533, 2020

PubMed Abstract: Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physicochemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model.

PubMed: 32919012
DOI: 10.1016/j.bmcl.2020.127533

実験手法

X-RAY DIFFRACTION (2.04 Å)