8BOE

Human Carbonic Anhydrase I in complex with (S)-4-(3-(1-(6-nitropyridin-2-yl)pyrrolidin-3-yl)thioureido)benzenesulfonamide

これはPDB形式変換不可エントリーです。

8BOE の概要

• エントリーDOI: 10.2210/pdb8boe/pdb
• 分子名称: Carbonic anhydrase 2, GLYCEROL, ZINC ION, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase ii, metalloenzyme, inhibitor, sulfonamide, lyase
• 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: 29869.05

構造登録者

Angeli, A.,Ferraroni, M. (登録日: 2022-11-15, 公開日: 2023-11-29, 最終更新日: 2026-03-04)

主引用文献

Angeli, A.,Micheli, L.,Carta, F.,Ferraroni, M.,Pirali, T.,Fernandez Carvajal, A.,Ferrer Montiel, A.,Di Cesare Mannelli, L.,Ghelardini, C.,Supuran, C.T.
First-in-Class Dual Hybrid Carbonic Anhydrase Inhibitors and Transient Receptor Potential Vanilloid 1 Agonists Revert Oxaliplatin-Induced Neuropathy.
J.Med.Chem., 66:1616-1633, 2023

PubMed Abstract: Here, we report for the first time a series of compounds potentially useful for the management of oxaliplatin-induced neuropathy (OINP) able to modulate the human Carbonic Anhydrases (hCAs) as well as the Transient Receptor Potential Vanilloid 1 (TRPV1). All compounds showed effective inhibition activity toward the main hCAs involved in such a pathology, whereas selected items reported moderate agonism of TRPV1. X-ray crystallographic experiments assessed the binding modes of the two enantiomers ()- and ()- within the hCA II cleft. Although the tails assumed diverse orientations, no appreciable effects were observed for their hCA II affinity. Similarly, the activity of ()- and ()- on TRPV1 was not influenced by the stereocenters. evaluation of the most promising derivatives ()-, ()-, and the two enantiomers ()-, ()- revealed antihypersensitivity effects in a mouse model of OINP with potent and persistent effect up to 75 min after administration.

PubMed: 36626645
DOI: 10.1021/acs.jmedchem.2c01911

実験手法

X-RAY DIFFRACTION (1.55 Å)