7N7X

Crystal structure of BCX7353(ORLADEYO) in complex with human plasma kallikrein serine protease domain at 2.1 angstrom resolution

これはPDB形式変換不可エントリーです。

7N7X の概要

• エントリーDOI: 10.2210/pdb7n7x/pdb
• 関連するPDBエントリー: 2ANW 2ANY 5tjx
• 分子名称: Plasma kallikrein light chain, Orladeyo, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: kallikrein, blood, plasma, plasma kallikrein-mediated edema, acute hereditary angioedema, hae, hmwk, hereditary angioedema, haw, bradykinin, fletcher factor, kininogenin, serine protease, edema, orladeyo, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 27326.90

構造登録者

Krishnan, R.,Yarlagadda, B.S.,Kotian, P.,Polach, K.J.,Zhang, W. (登録日: 2021-06-11, 公開日: 2021-09-15, 最終更新日: 2024-11-20)

主引用文献

Kotian, P.L.,Wu, M.,Vadlakonda, S.,Chintareddy, V.,Lu, P.,Juarez, L.,Kellogg-Yelder, D.,Chen, X.,Muppa, S.,Chambers-Wilson, R.,Davis Parker, C.,Williams, J.,Polach, K.J.,Zhang, W.,Raman, K.,Babu, Y.S.
Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE).
J.Med.Chem., 64:12453-12468, 2021

PubMed Abstract: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration's approval for the prophylactic treatment of HAE attacks in patients 12 years and older.

PubMed: 34436898
DOI: 10.1021/acs.jmedchem.1c00511

実験手法

X-RAY DIFFRACTION (2.097 Å)