预约演示

更新于：2025-05-07

autotaxin

更新于：2025-05-07

基本信息

别名

ATX、Autotaxin、E-NPP 2

+ [7]

简介

Secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12354767, PubMed:14500380, PubMed:15769751, PubMed:26371182, PubMed:27754931). Its major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:14500380, PubMed:27754931). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:12176993, PubMed:15769751). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252).

关联

项与 autotaxin 相关的药物

HW021199

靶点

autotaxin

作用机制

autotaxin抑制剂

在研机构

湖北生物医药产业技术研究院有限公司 [+1]

原研机构

湖北生物医药产业技术研究院有限公司

在研适应症

特发性肺纤维化

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

BBT-877

靶点

autotaxin

作用机制

autotaxin抑制剂

在研机构

Bridge Biotherapeutics, Inc.

原研机构

LigaChem Biosciences, Inc.

在研适应症

特发性肺纤维化

非在研适应症

非酒精性脂肪性肝炎

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

2ccPA

靶点

LPAR x autotaxin

作用机制

LPAR激动剂 [+1]

在研机构

Tokyo Women's Medical University Educational Association [+2]

原研机构

SANSHO Co. Ltd. (Tokyo) [+2]

在研适应症

膝关节炎 [+2]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 autotaxin 相关的临床试验

NCT06939504

/ Not yet recruiting临床1期

Evaluation of the Relative Bioavailability of HRS-9813 Capsule and Tablet in Healthy Subjects and the Effect of Food on the Pharmacokinetics of HRS-9813 Capsule

This is a phase Ⅰ study to evaluate the relative bioavailability of HRS-9813 capsule and tablet in healthy subjects and the effect of food on the pharmacokinetics of HRS-9813 capsule.

开始日期2025-05-01

申办/合作机构

广东恒瑞医药有限公司

NCT06821464

/ Not yet recruiting临床1期

Safety, Tolerability and Pharmacokinetics of HRS-9813 After Multiple Oral Administration in Healthy Subjects-A Phase I Clinical Study

The study is being conducted to evaluate the safety and pharmacokinetics of HRS-9813 after multiple oral administration in healthy subjects.

开始日期2025-02-01

申办/合作机构

广东恒瑞医药有限公司

NCT06514963

/ Completed临床1期

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect on the Pharmacokinetics of HRS-9813 Tablets After Single and Multiple Ascending Oral Doses in Healthy Volunteers

The purpose of this phase Ⅰ study is to evaluate the safety, tolerability and pharmacokinetics of HRS-9813 in healthy volunteers.

开始日期2024-07-24

申办/合作机构

广东恒瑞医药有限公司

100 项与 autotaxin 相关的临床结果

登录后查看更多信息

100 项与 autotaxin 相关的转化医学

登录后查看更多信息

0 项与 autotaxin 相关的专利（医药）

登录后查看更多信息

1,531

项与 autotaxin 相关的文献（医药）

2025-08-01·Bioorganic & Medicinal Chemistry Letters

Optimization of a DNA encoded library derived autotaxin inhibitor hit to a potent in vivo LPA lowering quinazolinone compound with a non‑zinc binding mode

Article

作者: Kuratli, Christoph ; Binder, Martin ; Satz, Alexander L ; Mattei, Patrizio ; Alker, André M ; Marx, Andreas ; Ullmer, Christoph ; Hunziker, Daniel ; Hert, Jérôme ; Müller, Stephan ; Martin, Rainer E ; Hochstrasser, Remo ; Rudolph, Markus G

In recent years, lysophospholipase autotaxin (ATX) has emerged as an attractive target for treating a variety of human diseases, including inflammation, neurodegeneration, angiogenesis, cancer, ocular and fibrotic diseases, among others. Starting with the quinazolinone hit structure 1, which emerged from a DNA-encoded library screen, the potent, non-Zn²⁺ binding ATX inhibitor 31 with good overall physicochemical properties has been developed. This compound demonstrated a sustained reduction of lysophosphatidic acid (LPA) in an in vivo rat experiment, qualifying it as a proof-of-concept compound for further mechanistic studies.

2025-07-01·European Journal of Medicinal Chemistry

The Groebke–Blackburn–Bienaymé (GBB) reaction: A powerful tool for generating diverse heterocyclic scaffold libraries in anticancer drug discovery

Review

作者: Saquib, Mohammad ; Kumar, Promod ; Hussain, Mohd Kamil ; Khan, Amzad ; Ahamad, Shakir ; Khatoon, Shahnaaz ; Khan, Khizra ; Ali, Rashid

The Groebke-Blackburn-Bienaymé (GBB) reaction is a versatile multi-component (MCR) synthetic methodology that has transformed anticancer drug discovery by enabling the rapid and efficient generation of diverse heterocyclic scaffolds. These scaffolds, such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and their derivatives, are highly valuable moieties for targeting critical cancer pathways. The modular nature of the GBB reaction, coupled with post-reaction modifications, allows the design of compounds with tailored structures and enhanced pharmacological properties. GBB-derived compounds exhibit broad anticancer potential by modulating diverse molecular targets. These include protein kinases (e.g. Rock2, Gsk3β, B-Raf), microtubule dynamics via tubulin inhibition, and G-quadruplex DNA stabilization in oncogene promoters (e.g., c-MYC, BCL2), disrupting key mechanisms of tumour progression. Moreover, they target epigenetic regulators such as HDACs, CBP/P300 bromodomains, and BET bromodomains, affecting transcriptional regulation and chromatin remodeling. Immune checkpoints (e.g., PD-1/PD-L1), enzymes such as autotaxin, TDP1, and Hsp90, as well as apoptotic regulators (e.g., Bcl-2, BAG3), are also effectively inhibited. More importantly, these compounds address challenging targets, including KRAS G12C mutations and the menin-MLL interaction, offering solutions to previously "undruggable" pathways. The unparalleled efficiency of GBB reaction and its ability to generate structurally diverse, bioactive compounds spanning multiple oncogenic mechanisms highlights its central role in advancing anticancer drug discovery and its transformative impact on therapeutic innovation.

2025-07-01·European Journal of Pain

Comparative Analysis of Lysophosphatidic Acid Levels in Fibromyalgia and Other Painful Conditions in Female Patients

Article

作者: Venckute Larsson, Sigita ; Jakobsson, Jenny E. ; Svensson, Camilla I. ; Kultima, Kim ; Menezes, Joana ; Krock, Emerson ; Hunt, Matthew A. ; Kosek, Eva ; Tanum, Lars ; Simon, Nils ; Bersellini Farinotti, Alex

ABSTRACTBackgroundPrevious work found a decrease in lysophosphatidylcholines (LPCs) in fibromyalgia (FM) serum, prompting the hypothesis that this decrease could be due to increased conversion of LPC to lysophosphatidic acid (LPA) through autotaxin (ATX). LPA has pronociceptive functions, and increased LPA levels could modulate FM pain.MethodsThis study quantified LPA levels in serum and lumbar cerebrospinal fluid (CSF) and serum ATX levels in FM patients, comparing with healthy controls (HCs), osteoarthritis (OA), degenerative disc disease (DDD) and lumbar disc herniation (LDH) patients.ResultsWe found increased serum LPA levels in FM and OA patients, with no changes in FM lumbar CSF. Unexpectedly, a positive correlation between serum LPA and conditioned pain modulation was observed in FM patients, while LPA levels were correlated with pain intensity and Knee Injury and Osteoarthritis Outcome Scores in OA. Serum ATX levels in FM patients were comparable to those in HC but correlated significantly with FM LPA levels (in one cohort), as well as with pain duration and the maximal weekly pain intensity.ConclusionsThis study suggests that increased LPA levels play distinct roles in FM and OA patients. In FM, LPA levels were linked to less impaired inhibitory pain pathways, while LPA levels in OA correlated with pain intensity and knee‐related impairment. ATX levels in FM serum are associated with pain intensity and duration. These findings underscore the complex role of LPA and ATX in FM pathophysiology. Future studies are essential to clarify LPA's specific roles and to develop therapies.Significance StatementThis study provides novel insights into the role of LPA in FM and other chronic pain conditions. Although ATX levels were unchanged in FM, a positive correlation between serum ATX and LPA supports the role of ATX in LPA conversion. These findings suggest complex lipid dysregulation in FM, with LPA potentially modulating pain pathways. Further research is needed to clarify LPA's role and its potential as a biomarker or therapeutic target.

项与 autotaxin 相关的新闻（医药）

2025-04-04

·药学进展

学科前沿|沈阳药科大学在ATX抑制剂治疗肺纤维化领域取得新进展

“点击蓝字关注我们沈阳药科大学在ATX抑制剂治疗肺纤维化领域取得新进展 PPS 近日（03.23.2025 Online），药物化学学科国际期刊Journal of Medicinal Chemistry（IF = 6.9）在线发表了沈阳药科大学翟鑫教授课题组在ATX抑制剂治疗肺纤维化领域取得的最新研究成果，论文题目为“Development of Tricyclic 4,5-Dihydro‑3H‑pyrrolo[2,3‑c]quinolin-4-ones as Potent Autotaxin Inhibitors for Pulmonary Fibrosis Treatment In Vivo”。自分泌运动因子（ATX）是人体内唯一具有溶血磷脂酶D活性的酶类，能催化溶血磷脂酰胆碱（LPC）水解为溶血磷脂酸（LPA），在纤维化疾病的发生和发展过程中发挥着关键作用。ATX作为肺纤维化治疗靶点得到广泛研究，多个有活性的小分子抑制剂被相继报道。该课题组前期以处于II期临床研究的ATX抑制剂PAT-409为先导化合物，运用局部修饰和骨架跃迁等策略，结合计算机辅助药物设计，获得了一系列以4,5,6,7-四氢-7H-吡唑并[3,4-c]哌啶-7-酮为核心骨架的新型ATX变构抑制剂，在体内外表现出了较好的肺纤维化治疗效果。在此基础上，采用环融合策略，对该类化合物开展了进一步的结构改造，设计并得到了一系列4,5-二氢-3H-吡咯并[2,3-c]喹啉-4-酮类三环骨架的新型ATX变构抑制剂。经过系统的构效关系研究，获得了优选化合物45（IC50 = 0.86 nM）和46（IC50 = 0.97 nM）。酶动力学实验证实，化合物45和46以非竞争性抑制的方式发挥ATX酶抑制活性。在胚胎成纤维细胞MRC-5中，化合物45和46能显著抑制TGF-β1诱导的细胞迁移和纤维化相关基因的表达，显示出较好的抗纤维化潜力。在博来霉素诱导的小鼠肺纤维化模型中，经化合物45和46治疗后，其呼吸窘迫症状，肺组织炎症细胞浸润、胶原沉积等纤维化症状得到明显缓解。hERG实验以及心、肝、脾和肾的病理学分析表明化合物45和46具有良好的心脏安全性以及治疗剂量下的体内安全性。Western blot分析阐明，化合物45通过抑制TGF-β/Smad信号通路发挥抗纤维化作用。该校2021级药物化学专业博士研究生马德翊为论文第一作者，制药工程学院翟鑫教授、类红瑞特聘教授和生命科学与生物制药学院臧凌鹤副教授为共同通讯作者，沈阳药科大学为第一通讯单位。该研究工作得到了国家自然科学基金面上项目（NO. 82104003 & 81872751）的资助。文章来源：沈阳药科大学美编排版：杨雨菲文章审核：童景阳杨雨菲杨美帆【免责声明】以上内容来源于互联网，不代表本平台立场或观点；如有侵犯作者著作权，请及时与我们联系（Tel：025-83271227，或直接在微信平台留言），我们将及时更正或删除。《药学进展》杂志由国家教育部主管、中国药科大学和中国药学会共同主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.216，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

临床2期临床终止临床结果

2025-02-11

·药时代

核心管线折戟，Pliant股价雪崩

股价暴跌60% 2025年2月9日，Pliant Therapeutics宣布暂停其核心管线bexotegrast用于特发性肺纤维化（IPF）的IIb/III期BEACON-IPF研究。新闻稿中指出，此决定是基于数据安全监查委员会（DSMB ）给出的建议。DSMB主要职能为保证受试者安全和利益，以及确保试验的完整性和可信性，具体到职责则为”就继续、修改或停止试验向申办方提出建议”。在原计划中，Pliant打算在本季度完成BEACON-IPF研究IIb期的患者入组，并预计在2026年年中公布数据。此次突然宣布终止研究，Pliant并未披露详细原因。该公司表示，在数据审查以了解DSMB的决策理由期间，试验仍将保持盲态。受此消息影响，Pliant当日收盘股价暴跌60.59%，报3.07美元/股。十年困局：IPF治疗领域的新药荒漠 IPF是一种病因未明，局限于肺部的纤维化间质性肺炎。普通人群中的患病率2/100 000～ 29/100 000，属于罕见病。随着疾病的进展，影像学上可以观测到患者肺组织会变厚、变硬、类似出现疤痕，使患者的肺呈大小不等的囊性状，也被成为“蜂窝肺”。图片来源：默沙东诊疗手册十年前，IPF的治疗是传统“三板斧”，即激素、免疫抑制剂（如环玲酰胺、硫唑嘌呤）和抗氧化剂乙酰半胱氨酸，疗效差强人意。 2014年，随着吡非尼酮与尼达尼布两款抗纤维化药物获FDA批准上市，有效延缓了患者的肺纤维化进展，提高生活质量。其中，吡非尼酮是通过抑制细胞因子转化生长因子β（TGF-β）来抑制纤维化过程，而尼达尼布则是广泛抑制成纤维细胞和肌成纤维细胞中的下游信号通路。虽然两款药物均都能抑制成纤维细胞增殖、阻碍胶原蛋白的产生并减少纤维化介质的产生，但不可避免的是都会产生显著的不良反应。一项真实世界研究的荟萃分析发现，吡非尼酮和尼达尼布的不良反应发生率分别高达56.4%和69.7%，因不良反应中断治疗率分别为16.6%和16.2%，IPF相关死亡率分别为13.4%和7.2%，全因死亡率分别为20.1%和16.6%。更为重要的是，十年过去，IPF抗纤维化药物仍且只有这两款药物获批上市。而这两种药物都不能阻止IPF的进展，预后差，患者诊断后平均存活约 3-5 年，存在巨大未被满足的临床需求。难以穿越的研发“死亡谷” 市场的长期“空白”，并不意味着IPF领域没有投资潜力。据弗若斯特沙利文统计，2021年全球IPF的市场规模为33亿美元，预计2025年、2030年可达到50亿美元、71亿美元。从吡非尼酮与尼达尼布的销售额来看，2020年两款药物的全球合并销售额约为35亿美元。可以说，两款“孤儿药”双双跻身重磅炸弹之列。值得一提的是，随着专利悬崖与仿制药冲击，本月（2025年2月），罗氏宣布将其InterMune部门（包括吡非尼酮在美权益）出售给了Legacy Pharma。据罗氏2024财报显示，吡非尼酮全球销售额已跌至5400万美元。可以看出，两款药物基本实现了仿制替代。那么为何，十年时间仍无IPF创新药获批？因为难。一方面，疾病机制复杂，靶点选择与验证难度高。 IPF的发病机制尚未完全阐明，涉及炎症反应、上皮细胞损伤、成纤维细胞异常活化、细胞外基质沉积等多条信号通路（如TGF-β、CTGF、PDE4、整合素αvβ6等）。尽管靶向这些通路的药物被广泛研究，但部分关键靶点在临床试验中未能验证其有效性。例如，针对CTGF的单抗Pamrevlumab、针对ATX的Ziritaxestat等III期试验均因疗效不足而失败。另一方面，临床前模型与人体均在差异。动物模型（如博来霉素诱导肺纤维化）无法完全模拟人类IPF的复杂病理过程，从而无法筛选出最佳的候选药物。此外，目前IPF的诊断和疗效评估主要依赖肺功能指标（如FVC）和影像学（HRCT），缺乏可预测疾病进展或药物反应的分子标志物。总而言之问题很多，近年来不少Biotech与MNC折戟于此，以至于业内将IPF的临床二期称为“死亡谷”。也正因如此，bexotegrast被业内寄予厚望。该药物作为一款口服小分子αvβ6与αvβ1整合素双重选择性抑制剂，旨在阻断TGF-β的激活，进而阻止TGF-β与其受体结合并激活促纤维化信号通路。其IIa期研究表明，Bexotegrast治疗的患者总肺胶原减少，而安慰剂组的总肺胶原增加，表明纤维化可能逆转。与安慰剂组相比，接受Bexotegrast治疗的患者在所有时间点均表现出用力肺活量(FVC)改善和咳嗽严重程度降低。安全性方面，Bexotegrast耐受性良好，没有药物相关的严重不良事件(SAE)且没有停药。如今，作为Pliant首发管线的Bexotegrast，应声倒下，其股价暴跌也成了必然结果。破局曙光：差异化路径与新势力崛起人的悲欢并不相同。近日，BI宣布其选择性磷酸二酯酶4B（PDE4B）抑制剂Nerandomilast在用于治疗进行性肺纤维化（PPF）的试验中报阳。此前，Nerandomilast已在IPF的三期临床试验中取得积极结果，因此成为了十年来首个在IPF三期临床试验中达到主要终点的药物。目前，BI针对IPF领域押注了四款不同机制新药，除Nerandomilast外，还有TRPA1抑制剂BI 1839100、IL-11抗体BI-765423以及一款ATX抑制剂。后面三条管线均处在临床早期阶段。国内方面，英矽智能于去年11月，宣布其核心自研管线ISM001-055在用于IPF的2a期临床研究中结果报阳；恒瑞在放弃一款靶向CTGF的单克隆抗体之后，又于去年7月启动了一项ATX抑制剂HRS-9813用于治疗IDF的临床1期研究。最后就是交易方面，今年1月10日，礼来宣布斥资7.86亿美元从Mediar Therapeutics手中引入一款IPF在研药物MTX-463的全球权益，首付款和近期里程碑高达9900万美元。参考资料： 1.Pliant Therapeutics官网 2.默沙东诊疗手册 3.雪球 4.继恒瑞后，阿斯利康也在特发性肺纤维化新药开发实现“靶点换新”（新药前沿）5.当初罗氏83亿美元收购的公司，如今卖了，因为仿制药的冲击（新药说） 6.IPF新药，产生7.86亿美元BD大交易（药融圈） 6.其他公开资料封面图来源：pixabay 暴增超2000%！两款单抗，撑起阿尔茨海默病一片天 2025-02-10 罗氏CD20单抗三期临床结果积极，闯入蓝海自免市场！ 2025-02-08 核药：首个十亿美元分子诞生！ 2025-02-07 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击，查看更多精彩!

孤儿药上市批准临床2期临床结果

2024-12-30

·PRNewswire

Bridge Biotherapeutics to Present at the 43rd Annual J.P. Morgan Healthcare Conference

SEONGNAM, South Korea and BOSTON, Dec. 30, 2024 /PRNewswire/ -- Bridge Biotherapeutics (KQ288330), a clinical-stage biotech company based in South Korea developing novel drugs for fibrosis and cancer, today announced that James Jungkue Lee, Founder and CEO of Bridge Biotherapeutics, will present at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025. Location: Georgian Room (Mezzanine Level) at The Westin St. Francis Date: Thursday, January 16, 2025 Time: 9:45-10:25 a.m. PST During the conference, Bridge Biotherapeutics will also meet with potential partners and investors as the Company is looking for Business Development opportunities for further development of BBT-877, a novel drug candidate for idiopathic pulmonary fibrosis (IPF). Top-line results from the Phase 2 study of BBT-877 are expected in April 2025. To arrange a meeting with the Bridge Biotherapeutics team, send a meeting request here. About Bridge Biotherapeutics, Inc. Bridge Biotherapeutics Inc., based in the Republic of Korea and the U.S., is a publicly traded, clinical-stage biotech company founded in 2015. Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics, focusing on therapeutic areas with high unmet needs, including fibrotic diseases and cancers. The company is developing BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), and BBT-207, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with EGFR C797S mutations. Learn more at . SOURCE Bridge Biotherapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期