CTIBD(CTIBD) - 药物靶点：BK channel_在研适应症：膀胱过度活动症_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

BK channel

作用机制

BK channel激动剂(钙激活钾通道α/β1复合体激动剂)

治疗领域

泌尿生殖系统疾病

在研适应症

膀胱过度活动症

非在研适应症-

原研机构

Gwangju Institute of Science & Technology

在研机构

Gwangju Institute of Science & Technology

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-

结构

分子式C16H9ClF3NO3

InChIKeyBYNUBBWBGHJHNP-UHFFFAOYSA-N

CAS号879592-33-3

关联

100 项与 CTIBD 相关的临床结果

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100 项与 CTIBD 相关的转化医学

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100 项与 CTIBD 相关的专利（医药）

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1

项与 CTIBD 相关的文献（医药）

2024-10-01·Life Science Alliance

Activation mechanism and novel binding sites of the BK_Cachannel activator CTIBD

Article

作者: Kim, Subin ; Jo, Heeji ; Lee, Narasaem ; Jin, Mi Sun ; Park, Chul-Seung ; Lee, Na Young ; Pagire, Haushabhau S ; Jeong, Pyeonghwa ; Ahn, Jin Hee ; Pagire, Suvarna H

The large-conductance calcium-activated potassium (BKCa) channel, which is crucial for urinary bladder smooth muscle relaxation, is a potential target for overactive bladder treatment. Our prior work unveiled CTIBD as a promising BKCachannel activator, alteringV1/2andGmax. This study investigates CTIBD’s activation mechanism, revealing its independence from the Ca2+and membrane voltage sensing of the BKCachannel. Cryo-electron microscopy disclosed that two CTIBD molecules bind to hydrophobic regions on the extracellular side of the lipid bilayer. Key residues (W22, W203, and F266) are important for CTIBD binding, and their replacement with alanine reduces CTIBD-mediated channel activation. The triple-mutant (W22A/W203A/F266A) channel showed the smallestV1/2shift with a minimal impact on activation and deactivation kinetics by CTIBD. At the single-channel level, CTIBD treatment was much less effective at increasingPoin the triple mutant, mainly because of a drastically increased dissociation rate compared with the WT. These findings highlight CTIBD’s mechanism, offering crucial insights for developing small-molecule treatments for BKCa-related pathophysiological conditions.

100 项与 CTIBD 相关的药物交易

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