SBL-PX1-42(SBL-PX1-42) - 药物靶点：PANX1_在研适应症：炎症_专利_临床

概要

基本信息

药物类型

合成多肽

别名-

靶点

PANX1

作用机制

PANX1抑制剂(pannexin 1 inhibitors)

治疗领域

其他疾病

在研适应症

炎症

非在研适应症-

原研机构

Vrije Universiteit Brussel

在研机构

Vrije Universiteit Brussel

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 SBL-PX1-42 相关的临床结果

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100 项与 SBL-PX1-42 相关的转化医学

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100 项与 SBL-PX1-42 相关的专利（医药）

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1

项与 SBL-PX1-42 相关的文献（医药）

2023-09-28·Journal of medicinal chemistry1区 · 医学

Structure-Based Design and Synthesis of Stapled ¹⁰Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases.

1区 · 医学

Article

作者: Kwak, Brenda R ; Mayán, María D ; Caufriez, Anne ; Loris, Remy ; Tabernilla, Andrés ; Vinken, Mathieu ; Ballet, Steven ; Iaculli, Debora ; Rusiecka, Olga M ; Girardin, Yana ; Carpio, Laureano E ; Bes, Viviane ; Gozalbes, Rafael ; Lamouroux, Arthur ; Molica, Filippo ; Tournier, Malaury ; Martin, Charlotte

Following a rational design, a series of macrocyclic ("stapled") peptidomimetics of ¹⁰Panx1, the most established peptide inhibitor of Pannexin1 (Panx1) channels, were developed and synthesized. Two macrocyclic analogues SBL-PX1-42 and SBL-PX1-44 outperformed the linear native peptide. During in vitro adenosine triphosphate (ATP) release and Yo-Pro-1 uptake assays in a Panx1-expressing tumor cell line, both compounds were revealed to be promising bidirectional inhibitors of Panx1 channel function, able to induce a two-fold inhibition, as compared to the native ¹⁰Panx1 sequence. The introduction of triazole-based cross-links within the peptide backbones increased helical content and enhanced in vitro proteolytic stability in human plasma (>30-fold longer half-lives, compared to ¹⁰Panx1). In adhesion assays, a "double-stapled" peptide, SBL-PX1-206 inhibited ATP release from endothelial cells, thereby efficiently reducing THP-1 monocyte adhesion to a TNF-α-activated endothelial monolayer and making it a promising candidate for future in vivo investigations in animal models of cardiovascular inflammatory disease.

100 项与 SBL-PX1-42 相关的药物交易

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