更新于：2024-11-01

TRPM8

更新于：2024-11-01

基本信息

别名

Long transient receptor potential channel 6、LTrpC-6、LTrpC-6LTrpC6

+ [7]

简介

Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonist menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing. In prostate cancer cells, shows strong inward rectification and high calcium selectivity in contrast to its behavior in normal cells which is characterized by outward rectification and poor cationic selectivity. Plays a role in prostate cancer cell migration (PubMed:25559186). Isoform 2 and isoform 3 negatively regulate menthol- and cold-induced channel activity by stabilizing the closed state of the channel.

关联

项与 TRPM8 相关的药物

Menthol/Methyl Salicylate

薄荷脑/水杨酸甲酯

靶点

TRPA1 x TRPM8

作用机制

TRPA1激动剂 [+1]

在研机构

Hisamitsu Pharmaceutical Co., Inc.

原研机构

Hisamitsu Pharmaceutical Co., Inc.

在研适应症

疼痛

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2008-02-20

Ibuprofen/Levomenthol

布洛芬/左旋薄荷醇

靶点

COX x TRPA1 x TRPM8 x κ opioid receptor

作用机制

COX抑制剂 [+3]

在研机构

The Mentholatum Co.

原研机构

The Mentholatum Co.

在研适应症-

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

英国

首次获批日期1998-08-06

Levomenthol

左旋薄荷醇

靶点

TRPA1 x TRPM8 x κ opioid receptor

作用机制

TRPA1抑制剂 [+2]

在研机构

Fuji Pharma Co., Ltd.

原研机构

University Hospitals Cleveland Medical Center

在研适应症-

非在研适应症

肠道疾病

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1986-01-20

106

项与 TRPM8 相关的临床试验

NCT06660290 / Not yet recruiting临床3期

A Phase 3b Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes

The purpose of this study is to evaluate the proportion of ocular adverse events reported in subjects with dry eye disease (DED) between the intervention arm (0.003% AR-15512) and Refresh® Classic.

开始日期2025-01-01

申办/合作机构

Alcon Research Ltd.

NCT05932745 / Not yet recruitingN/AIIT

Examining Appeal and Addiction Potential of Novel E-cigarette Constituents Among Adults

This study is an examination of the influence of cooling components of WS-3, WS-23, and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults.

开始日期2024-11-01

申办/合作机构

Yale University

[+1]

NCT06544707 / Recruiting临床3期

A Phase 3b Open-Label Study Designed to Evaluate Tear Production Stimulated by 0.003% AR-15512

The purpose of this study is to evaluate tear production following acute administration of AR-15512 ophthalmic solution 0.003% (0.003% AR-15512) in subjects with dry eye disease (DED).

开始日期2024-10-15

申办/合作机构

Alcon Research Ltd.

100 项与 TRPM8 相关的临床结果

登录后查看更多信息

100 项与 TRPM8 相关的转化医学

登录后查看更多信息

0 项与 TRPM8 相关的专利（医药）

登录后查看更多信息

1,463

项与 TRPM8 相关的文献（医药）

2024-12-01·European Journal of Medicinal Chemistry

The multicomponent Passerini reaction as a means of accessing diversity in structure, activity and properties: Soft and hard vanilloid/cannabinoid modulators

Article

作者: Goutsiou, Georgia ; Fernandez-Carvajal, Asia ; Di Martino, Rita Maria Concetta ; Serafini, Marta ; Pessolano, Emanuela ; Bhela, Irene Preet ; Aprile, Silvio ; Pirali, Tracey ; Fernandez-Ballester, Gregorio ; Lamberti, Angela ; Ferrer-Montiel, Antonio

A growing body of evidence points to the existence of a crosstalk between the endovanilloid (EV)- and the endocannabinoid (EC) systems, leading to the concept of a single system based on a shared set of endogenous ligands and regulation mechanisms. The EV/EC system encompasses the ion channel TRPV1, the G protein coupled receptors CB1 and CB2, their endogenous ligands and the enzymes for biosynthesis and inactivation. Disorders in which the EV/EC interaction is involved are inflammation, pain, neurodegenerative diseases and disorders of bones and skin. In the present paper, with the aim of targeting the EV/EC system, the Passerini reaction is used in a diversity-oriented approach to generate a series of α-acyloxycarboxamides bearing different substructures that resemble endogenous ligands. Compounds have been screened for activity on TRPV1, CB1 and CB2 and metabolic stability in skin cells, liver subcellular fractions and plasma. This protocol allowed to generate agents characterized by a diverse activity on TRPV1, CB1 and CB2, as well as heterogeneous metabolic stability that could allow different routes of administration, from soft drugs for topical treatment of skin diseases to hard drugs for systemic use in inflammation and pain. Compared to natural mediators, these compounds have a better drug-likeness. Among them, 41 stands out as an agonist endowed with a well-balanced activity on both TRPV1 and CB2, high selectivity over TRPM8, TRPA1 and CB1, metabolic stability and synthetic accessibility.

2024-11-01·European Journal of Pharmacology

Protective effects of menthol against olanzapine-induced metabolic alterations in female mice

Article

作者: Bansal, Yashika ; Sodhi, Rupinder Kaur ; Kumar, Hemant ; Singh, Raghunath ; Bishnoi, Mahendra ; Kuhad, Anurag ; Kondepudi, Kanthi Kiran

AIMMetabolic comorbidities such as obesity type 2 diabetes, insulin resistance, glucose intolerance, dyslipidemia are the major contributors for lower life expectancy and reduced patient compliance during antipsychotic therapy in patients with severe mental illnesses such as schizophrenia, bipolar disorder, and depression. TRPM8 activation by menthol is also reported to alleviate high fat diet-induced obesity in mice. Additionally, this TRPM8 activation leads to increase in gene expression of thermogenic genes in white adipocytes and dietary menthol was found to increase browning of WAT along with improved glucose utilization. Therefore, we aimed to evaluate the plausible role of TRPM8 channels in olanzapine-induced metabolic alterations in female balb/c mice.METHODS6 weeks olanzapine (6 mg kg^-1, per oral) model was used in female balb/c mice. Pharmacological manipulation of TRPM8 channel was done using menthol and N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide (AMTB), the agonist and antagonist respectively.KEY RESULTSMenthol co-treatment for six weeks prevented olanzapine-induced metabolic alterations such as weight gain, increased food intake, decreased energy expenditure, adiposity, liver lipid accumulation, systemic inflammation and insulin resistance. Although no significant change in TRPM8 mRNA expression was found in the hypothalamus, however, some of the protective effects of menthol were absent in presence of AMTB indicating possible involvement of TRPM8 channels.CONCLUSIONOur results suggest possible therapeutic implications of menthol in the management of antipsychotic-induced weight gain and other metabolic alterations.

2024-11-01·Journal of Ethnopharmacology

Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway

Article

作者: Zhang, Shujing ; Zhou, Ranran ; Meng, Fengxian ; Ji, Xuenian ; Liu, Zijian ; Xu, Qianwei ; Ge, Dongyu ; Yu, Xue ; Tao, Xiaohua ; Qiu, Yuehua ; Zhao, Caihong ; Luo, Yamin ; Wang, Chunguo ; Ge, Fei ; Zhang, Yao ; Hou, Jianchen

ETHNOPHARMACOLOGICAL RELEVANCEPaeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine.AIM OF THE STUDYThis research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats.MATERIALS AND METHODSUsing a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques.RESULTSFollowing treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1β and TNF-α.CONCLUSIONSOur findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

项与 TRPM8 相关的新闻（医药）

2024-10-07

·医药观澜

刚刚！2024年诺贝尔生理学或医学奖正式揭晓

▎药明康德内容团队报道就在刚刚，备受瞩目的2024年诺贝尔生理学或医学奖重磅揭晓！Victor Ambros博士和Gary Ruvkun博士因发现microRNA及其在转录后基因调控中的作用共同获得这一奖项。图片来源：诺贝尔奖官网诺贝尔生理学或医学奖旨在表彰在生理学或医学领域作出重要发现或发明的人，并被普遍认为是这个领域能够取得的最高荣誉之一。该奖项自1901年首次颁发以来，共计颁发114次，超220人获得该奖。回顾这一个多世纪的历史，科学家们在基础科学上的深耕，已为许多疾病治疗带来范式改变。本文中就让我们来看看，哪些前沿研究和突破性进展斩获了近十年来的诺贝尔生理学或医学奖。 2023年获奖领域：通过核苷碱基修饰开发出mRNA疫苗获奖者：Katalin Karikó博士和Drew Weissman博士在新冠疫情中，基于mRNA技术的新冠疫苗以创纪录的速度登上历史舞台，为无数人带来了保护，也改变了全球对抗新冠疫情的格局。而在此前，mRNA技术的应用存在一个难以逾越的障碍——免疫系统会把合成的mRNA视为外物进行攻击，让它们无法生效。2023年两位诺奖得主将转运RNA（tRNA）上的化学修饰照搬到mRNA上后，修饰后的mRNA不再会引起额外的免疫反应，这解决了mRNA技术应用道路上的最大障碍。诺奖委员会表示，两位科学家通过核苷碱基修饰，使开发出有效的抗COVID-19 mRNA疫苗成为可能。（相关阅读） 2022年获奖领域：古基因组学研究获奖者：Svante Pääbo博士人类从何而来，我们与已灭绝的古人类之间有何联系？2010年，Svante Pääbo博士成功地对尼安德特人的基因组进行了测序。他还发现了一个以前不为人知的古人类丹尼索瓦人。大约7万年前，这些现已灭绝的古人类从非洲迁徙出来后，基因转移到了智人身上。Svante Pääbo博士建立了一门全新的科学学科——古基因组学，其研究成果也让人们明白那些灭绝亲戚的古代基因序列还影响了现在人类的生理学特征，例如影响了我们对多种感染的免疫反应。（相关阅读） 2021年获奖领域：发现感知温度和触觉的受体获奖者：David Julius博士、Ardem Patapoutian博士温度、触觉和运动产生的印象，对于我们适应周围这个不断变迁的世界至关重要。2021年两位诺奖得主在TRPV1、TRPM8、以及Piezo通道上的突破性贡献，不仅让我们知道人体如何感知冷热，感知触觉，从而理解身边的世界，后续的研究还为我们带来了更多生理上的洞见，也被用于开发多种治疗疾病的药物。这些疾病包括疼痛、呼吸道疾病、乃至癌症。可以说，他们的发现开辟了更多的疾病治疗可能。（相关阅读） 2020年获奖领域：丙型肝炎病毒的重要发现获奖者：Harvey J. Alter博士、Michael Houghton博士、以及Charles M. Rice博士血源性肝炎是一种全球健康问题，然而大多数血源性肝炎病例至今仍无法解释。2020年诺贝尔奖获得者们的发现，使针对丙肝的抗病毒治疗药物取得了快速的研究进展，使丙肝这种疾病在历史上第一次被治愈。此外，丙型肝炎病毒的发现揭示了其他慢性肝炎病例的病因，并使血液检测和新药开发成为可能，挽救了数百万人的生命。（相关阅读） 2019年获奖领域：发现氧气感知通路获奖者：William G. Kaelin教授、Peter J. Ratcliffe教授、Gregg L. Semenza教授动物需要氧气才能将食物转化为有用的能量。长期以来，氧气最基本的重要性已被大众熟知，但人们一直不清楚细胞如何适应氧气水平的变化。2019年的诺贝尔奖获得者们揭示了生命中最重要的适应过程之一的机制——细胞如何感知和适应不断变化的氧气水平，以及通过调节基因活性来应对不同氧气水平的分子机制。这为我们了解氧水平如何影响细胞代谢和生理功能奠定了基础，也为治疗贫血、癌症和许多其它疾病的新策略提供了新思路。（相关阅读） 2018年获奖领域：免疫疗法与癌症治疗获奖者：James Allison教授与Tasuku Honjo教授癌症每年造成数百万人死亡，是人类最大的健康挑战之一。这一年的诺贝尔奖获得者们建立了癌症治疗的一种全新机制——通过激发免疫系统的内在能力来攻击肿瘤细胞。其中，James Allison教授在动物实验中证明，抗CTLA-4抗体可增强免疫并起到抑癌的效果。Tasuku Honjo教授和他的课题组则筛选出了一系列可能参与程序性细胞死亡的cDNA，其中包括PD-1基因。基于CTLA-4和PD-1的研究，为免疫疗法研究领域带来了免疫检查点抑制剂，并最终将这一研究成果转化为造福患者的创新疗法。（相关阅读） 2017年获奖领域：控制昼夜节律的分子机制获奖者：Jeffrey C. Hall博士、Michael Rosbash博士、以及Michael W. Young博士在人体细胞中，“生物钟”可以帮助我们适应白天和黑夜的不断交替。这一年的诺贝尔奖获得者们以果蝇为模式生物，分离出了一条能控制日常生物节律的关键基因。他们的研究表明，这条基因编码的蛋白质会在晚上富集，并在白天降解。随后，他们又找到了一些额外的蛋白元件，进一步揭露了细胞内生物钟的作用机理。基于他们的努力，我们知道在包括人类在内的多细胞生物中，竟然有着同样的生物节律。 2016年获奖领域：细胞自噬机制获奖者：Yoshinori Ohsumi教授自噬是细胞内重要的物质分解代谢过程，在溶酶体的作用下，一些物质能被细胞回收利用。不过这一机制直到1990年代初才被广泛了解，当时Yoshinori Ohsumi教授进行了一系列突破性的酵母实验后，发现了自噬的作用机制并鉴定了对该过程重要的基因。他的发现为我们更好地理解自噬在很多生理过程的作用奠定了基础，如细胞如何适应饥饿或者应对感染，某些遗传性或神经性疾病、癌症如何发生等。 2015年获奖领域：抵抗蛔虫寄生虫感染的新疗法以及抗疟疾的新疗法获奖者：William C. Campbell教授、Satoshi Ōmura教授以及科学家屠呦呦许多严重的传染病是由寄生虫感染引起。2015年的诺奖获得者们，研究出了对抗一些极具伤害性的寄生虫病的革命性疗法，为每年数百万感染人群提供了强有力的治疗手段，在改善人类健康和减少患者病痛方面意义重大。其中，Satoshi Ōmura教授培养的细菌会产生抑制其他微生物生长的物质，他还成功地培养出一种菌株。William Campbell教授从该菌株中纯化了一种阿维菌素，被证明对抵抗河盲症和淋巴丝虫病有效。科学家屠呦呦则通过对传统草药的研究，提取出一种抑制疟疾的物质——青蒿素。 2014年获奖领域：对构成大脑定位系统的细胞的发现获奖者：John O'Keefe教授、May-Britt Moser教授和Edvard I. Moser博士确定自已的位置以及找到通往其他地方的路，对于人和动物的生存是至关重要的。为了了解我们的空间定位能力，John O'Keefe教授研究了大鼠运动和海马神经元信号。1971年，他发现当老鼠位于房间中的某个位置时，某些细胞被激活，而当老鼠移动到另一个位置时，其他细胞也被激活。也就是说，这些细胞形成了房间的内部图。2005年5月，Britt Moser教授和Edvard I. Moser博士发现了一种细胞类型，该细胞类型对于确定靠近海马体的位置很重要。他们发现，当老鼠经过空间中排列成六边形网格的某些点时，就会激活形成导航坐标系的神经细胞。此后，他们继续展示了这些不同细胞类型如何协同作用。如开头所说，诺贝尔生理学或医学奖自首次颁发以来，已有200多位科学家获得这一奖项。生命不息，科学不止。我们致敬这些在这个关乎人类健康的关键领域做出重要贡献的科学前辈们，也希望未来看到更多突破性进展，并最终转化为能够造福人类的临床成果。参考资料： [1]The Nobel Prize in Physiology or Medicine 2024. Retrieved Oct 07，2024, from https://www.nobelprize.org/prizes/medicine/ [2]官方公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权级其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

信使RNA疫苗

2024-09-19

·医药观澜

艾威药业干眼症1类新药完成1/2期临床研究患者招募

▎药明康德内容团队报道艾威药业（IVIEW Therapeutics）近日宣布，已完成其针对IVW-1001的1/2期临床试验的患者招募。IVW-1001是一种通过眼睑湿巾递送的新型TRPM8激动剂，用于治疗干眼症的症状和体征。该公司预计将在2025年第一季度报告初步数据。干眼症（干眼）是一种常见又复杂的眼科疾病，影响着全球数百万人。干眼症可引起持续的刺痛、烧灼感、对光敏感、视力模糊和眼疲劳。艾威药业开发的1类创新药IVW-1001可通过对TRPM8冷感受体激动剂机制，针对干眼症的潜在原因，提供一种有潜力的新型治疗选择。另外，该在研药采用了通过眼睑擦拭的创新给药途径。公开资料显示，TRPM8（瞬时受体电位M8）是一种冷敏感受体，它们能够感知因为眼泪挥发导致的角膜温度下降，提高该受体活性可以增加基线的眼泪分泌和眨眼的频率。针对该靶点开发激动剂可以促进眼泪分泌，迅速改善干眼症症状。这与现有的抗炎症、抗氧化产品及人工泪液有所不同，也代表着治疗干眼症的一种创新机制。 “我们非常高兴在IVW-1001的临床开发中达成这一重要里程碑，”iView Therapeutics的首席医学顾问、眼科医生Houman Hemmati博士表示。“完成患者入组使我们更接近于为干眼症患者提供潜在的新治疗选择。我们热切期待试验结果，并对其可能对患者治疗的影响保持乐观。” 艾威药业的联合创始人、董事长兼首席执行官Bo Liang博士表示：“提前完成患者招募证明了我们临床团队的奉献精神以及眼科界对产品的浓厚兴趣。IVW-1001独特的TRPM8激活机制和通过眼睑湿巾进行的创新递送方式，可能为全球干眼症患者提供差异化的治疗选择。我们期待在临床结果分析后尽快分享我们的研究发现。” 参考资料： [1] 艾威药业新闻稿. 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床终止临床研究疫苗

2024-09-17

·PRNewswire

IVIEW Therapeutics Inc. Completes Patient Recruitment for Phase 1/2 Trial of IVW-1001 Ophthalmic Eyelid Wipe in Dry Eye Disease Patients

CRANBURY, N.J., Sept. 17, 2024 /PRNewswire/ -- IVIEW Therapeutics Inc., a clinical-stage biotechnology company dedicated to advancing innovative treatments for ocular diseases, today announced the completion of patient recruitment for its Phase 1/2 clinical trial evaluating IVW-1001, a novel TRPM8 agonist delivered via ophthalmic eyelid wipe, for the treatment of signs and symptoms of dry eye disease. The company anticipates reporting topline data in the first quarter of 2025. Advancing Toward Promising Results "We are thrilled to have reached this significant milestone in our clinical development program for IVW-1001," said Houman Hemmati, MD, PhD, Chief Medical Advisor at IVIEW Therapeutics Inc. "Completing patient enrollment brings us one step closer to potentially offering a new therapeutic option for individuals suffering from dry eye disease. We are eagerly awaiting the trial results and remain optimistic about the potential impact on patient care." A Step Forward in Innovative Ophthalmic Treatments Bo Liang, PhD, MBA, Co-founder, Chairman, and CEO of IVIEW Therapeutics Inc., commented, "The completion of patient recruitment ahead of schedule is a testament to the dedication of our clinical team and the interest from the ophthalmic community. IVW-1001's novel mechanism of TRPM8 activation and its innovative delivery through an ophthalmic eyelid wipe could offer a differentiated treatment for dry eye disease worldwide. We look forward to sharing our findings as soon as they are available." About IVIEW Therapeutics Inc. IVIEW Therapeutics Inc. is a clinical-stage biotechnology company focusing on innovative ophthalmic therapeutics. Driven by the pursuit of cutting-edge science, we aim to develop differentiated products that fulfill unmet medical needs. We invest in novel mechanisms of action and advanced drug delivery technology platforms to bring forward assets with potentially superior target product profiles. Our innovative portfolio of small molecules and gene therapy assets covers dry eye, myopia, conjunctivitis, glaucoma, and presbyopia. Located in Cranbury, New Jersey, IVIEW operates a state-of-the-art 11,045 sq. ft. laboratory and office space in the Princeton area. For additional information, please visit our website at . SOURCE IVIEW Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED