GRC-17536(GRC-17536) - 药物靶点：TRPA1_在研适应症：糖尿病周围神经病变_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

TRPA1

作用机制

TRPA1抑制剂(瞬时受体电位离子通道亚基1抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症

糖尿病周围神经病变

非在研适应症

周围神经损伤难治性慢性咳嗽

原研机构

Glenmark Pharmaceuticals Ltd.

在研机构

Ichnos Sciences SA

非在研机构

Glenmark Pharmaceuticals Ltd.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H13F5N4O3S2

InChIKeyXOPMVFNBFICPDB-UHFFFAOYSA-N

CAS号1246761-03-4

关联

13

项与 GRC-17536 相关的临床试验

CTRI/2021/08/035410 / Recruiting临床2期

A Phase 2b, randomized, double-blind, placebo controlled dose-finding study to evaluate efficacy, safety and tolerability of GRC 17536 in patients with painful diabetic peripheral neuropathy.

开始日期2021-08-12

申办/合作机构

Glenmark Specialty SA

CTRI/2020/09/028094 / Completed临床1期

A single-dose, phase 1 study to evaluate the pharmacokinetics of novel formulations of ISC 17536 in healthy male adults

开始日期2020-10-02

申办/合作机构

Glenmark Pharmaceuticals Ltd.

[+1]

NL-OMON42613 / CompletedN/A

A phase I study to investigate the pharmacokinetics, safety and tolerability of four different dosing regimens of GRC 17536 in healthy male volunteers using tablet formulation. - GRC 17536 multiple dose study in healthy volunteers.

开始日期2015-03-26

申办/合作机构

Ichnos Sciences SA

100 项与 GRC-17536 相关的临床结果

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100 项与 GRC-17536 相关的转化医学

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100 项与 GRC-17536 相关的专利（医药）

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6

项与 GRC-17536 相关的文献（医药）

2023-01-26·Journal of Medicinal Chemistry1区 · 医学

Discovery of BAY-390, a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist

1区 · 医学

Article

作者: Elves, Philip ; Coelho, Anne-Marie ; Walter, Daryl ; Mesch, Stefanie ; Hess, Stephen ; Zollner, Thomas M. ; Flanagan, Stuart ; Bäurle, Stefan ; Bothe, Ulrich ; Rotgeri, Andrea ; Basting, Daniel ; Pearson, Christopher ; Laux-Biehlmann, Alexis ; Steinmeyer, Andreas ; Jenkins, James ; Nawaz, Schanila ; Miyatake Ondozabal, Hideki

Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof is linked to a variety of painful conditions. Preclinical studies have demonstrated the role of TRPA1 receptors in a broad range of animal models of acute, inflammatory, and neuropathic pain. In addition, a clinical study using the TRPA1 antagonist GRC-17536 (Glenmark Pharmaceuticals) demonstrated efficacy in a subgroup of patients with painful diabetic neuropathy. Consequently, there is an increasing interest in TRPA1 inhibitors as potential analgesics. Herein, we report the identification of a fragment-like hit from a high-throughput screening (HTS) campaign and subsequent optimization to provide a novel and brain-penetrant TRPA1 inhibitor (compound 18, BAY-390), which is now being made available to the research community as an open-source in vivo probe.

2020-09-01·Expert Opinion on Therapeutic Patents2区 · 医学

Transient receptor potential ankyrin 1 (TRPA1) antagonists: a patent review (2015–2019)

2区 · 医学

Review

作者: Terrett, Jack A. ; Chen, Huifen

INTRODUCTIONTRPA1 is a non-selective cation channel predominantly expressed in sensory neurons, and functions as an irritant sensor for a plethora of noxious external stimuli and endogenous ligands. Due to its involvement in pain, itch, and respiratory syndromes, TRPA1 has been pursued as a promising drug target.AREAS COVEREDIn this review, the small molecule patent literature of TRPA1 antagonists from 2015-2019 was surveyed. The patent applications are described with a focus on chemical structures, biochemical/pharmacological activities, and potential clinical applications. The development of TRPA1 antagonists in clinical trials has been highlighted.EXPERT OPINIONDuring 2015-2019, significant progress was made toward the discovery of new TRPA1 antagonists. A total of 14 organizations published 28 patent applications disclosing several distinct classes of chemical matter and potential uses. During this period, three new molecules entered the clinic (ODM-108, HX-100, and GDC-0334) bringing the total number of TRPA1 antagonists to reach clinical trials to five (including earlier molecules CB-625 and GRC 17536); however, to our knowledge, development of all five molecules have been discontinued. Further clinical trials of recent TRPA1 antagonists with good pharmacokinetics would be needed to help understand TRPA1 involvement in human diseases and its potential as a therapeutic target.

2017-01-01·Progress in Medicinal Chemistry

Recent Progress in the Discovery and Development of TRPA1 Modulators

Review

作者: Skerratt, S

TRPA1 is a well-validated therapeutic target in areas of high unmet medical need that include pain and respiratory disorders. The human genetic rationale for TRPA1 as a pain target is provided by a study describing a rare gain-of-function mutation in TRPA1, causing familial episodic pain syndrome. There is a growing interest in the TRPA1 field, with many pharmaceutical companies reporting the discovery of TRPA1 chemical matter; however, GRC 17536 remains to date the only TRPA1 antagonist to have completed Phase IIa studies. A key issue in the progression of TRPA1 programmes is the identification of high-quality orally bioavailable molecules. Most published TRPA1 ligands are commonly not suitable for clinical progression due to low lipophilic efficiency and/or poor absorption, distribution, metabolism, excretion and pharmaceutical properties. The recent TRPA1 cryogenic electron microscopy structure from the Cheng and Julius labs determined the structure of full-length human TRPA1 at up to 4Å resolution in the presence of TRPA1 ligands. This ground-breaking science paves the way to enable structure-based drug design within the TRPA1 field.

100 项与 GRC-17536 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
周围神经损伤	临床2期	德国	Glenmark Pharmaceuticals Ltd.	2012-03-16
周围神经损伤	临床2期	英国	Glenmark Pharmaceuticals Ltd.	2012-03-16
难治性慢性咳嗽	药物发现	英国	Ichnos Sciences SA	2013-07-11
糖尿病周围神经病变	药物发现	捷克	Glenmark Pharmaceuticals Ltd.	2012-11-01
糖尿病周围神经病变	药物发现	印度	Glenmark Pharmaceuticals Ltd.	2012-11-01
糖尿病周围神经病变	药物发现	德国	Glenmark Pharmaceuticals Ltd.	2012-11-01
糖尿病周围神经病变	药物发现	英国	Glenmark Pharmaceuticals Ltd.	2012-11-01
周围神经损伤	药物发现	德国	Glenmark Pharmaceuticals Ltd.	2012-03-16
周围神经损伤	药物发现	英国	Glenmark Pharmaceuticals Ltd.	2012-03-16