A Two-Part Study of REC-994 in the Treatment of Adults With Symptomatic Cerebral Cavernous Malformation (CCM); Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994

This is a two-part, multi-center, randomized, double-blind, placebo-controlled study to investigate the safety, efficacy and pharmacokinetics of REC-994 (200 mg and 400 mg) compared to placebo in subjects with symptomatic cerebral cavernous malformation (CCM).

开始日期2022-03-17

申办/合作机构

Recursion Pharmaceuticals, Inc.

NCT04729595 / Terminated临床2/3期

A Phase 2/3, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study to Examine the Effects of Tempol (MBM-02) in Subjects With COVID-19 Infection

An Adaptive, Randomized, Double-blind, Placebo-controlled study to examine the Effects of Tempol in subjects with COVID-19 infection.

开始日期2021-09-01

申办/合作机构

DMK Pharmaceuticals Corp.

NCT04887311 / Unknown status临床2期

An Open Label Study to Assess the Safety and Efficacy of MBM-01 for the Treatment of Ataxia Telangiectasia

Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein.
The active compound in MBM-01 (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) may substitute for the loss of ATM by protecting cells from DNA damage, preventing and reducing oxidative damage, triggering an increase in cellular survival proteins, and preserving the brain and peripheral immune system.

开始日期2021-07-01

申办/合作机构

Matrix Biomed, Inc.

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100 项与 Tempol 相关的临床结果

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100 项与 Tempol 相关的转化医学

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100 项与 Tempol 相关的专利（医药）

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2,024

项与 Tempol 相关的文献（医药）

2024-12-31·CLINICAL AND EXPERIMENTAL HYPERTENSION

Gestational diabetes causes hyperactivity of the sympathetic nervous system and hypertension in adult mice offspring.

Article

作者: Wang, Chunxiang ; Luo, Hao ; Zhu, Jun ; Zhu, Xingyu ; Yang, Li ; Hu, Zegang ; Bai, Xue

BACKGROUND:

Gestational diabetes can lead to increased blood pressure in offspring, accompanied by impaired renal sodium excretion function and vasoconstriction and diastole dysfunction. However, there are few studies on whether it is accompanied by increased sympathetic nerve activity.

METHODS:

Pregnant C57BL/6 mice were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at day 0 of gestation. The mice of control mother offspring (CMO) and diabetic mother offspring (DMO) at 16 weeks of age were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or tempol (1 mmol/L, 0.4 μL/h) into the bilateral paraventricular nucleus (PVN) of mice for 4 weeks, respectively.

RESULTS:

Compared with CMO group, SBP and peripheral sympathetic nerve activity (increased heart rate, LF/HF and plasma norepinephrine and decreased SDNN and RMSSD) were increased in DMO group, which was accompanied by increased angiotensin II type-1 receptor (AT₁R) expression and function in PVN. The increase in AT₁R expression levels was attributed to a decrease in the methylation level of the AT₁R promoter region, resulting in an increase in AT₁R mRNA levels in PVN of DMO. Moreover, compared with CMO group, the levels of oxidative stress were increased and DNMT1 expression was decreased in PVN of DMO. Bilateral PVN infusion of tempol attenuated oxidative stress increased the level of DNMT1 expression and the binding of DNMT1 to the AT₁R promoter region, which reduced mRNA and protein expression level of AT₁R, heart rate and SBP in DMO, but not in CMO.

CONCLUSIONS:

The present study provides evidence for overactive sympathetic nervous systems in the pathogenesis of gestational diabetes-induced hypertension in offspring. Central antioxidant intervention in the PVN may be an important treatment strategy for fetal-programmed hypertension.

2024-12-01·Molecular biology reports

4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) alleviates lung injury by inhibiting SIRT6-HIF-1α signaling pathway activation through the upregulation of miR-212-5p expression

Article

作者: Niu, Xiaoqun ; Li, Ran ; Cao, Yu ; Ai, Li ; Li, Yongxia ; Liu, Zhijuan

OBJECTIVE:

Obstructive sleep apnea is closely related to oxidative stress. 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) can scavenge reactive oxygen species (ROS) and ameliorate oxidative damage in the body. The mechanism by which Tempol alleviates chronic intermittent hypoxia-induced lung injury has rarely been reported. This study aimed to confirm the molecular mechanism by which Tempol alleviates lung injury.

METHODS:

The levels of miR-212-5p and Sirtuin 6 (SIRT6) in injured lungs were analyzed using bioinformatics. In vitro, intermittent hypoxia (IH) treatment induced hypoxia in BEAS-2B cells and we established a model of chronic intermittent hypoxia (CIH) in mouse using a programmed hypoxia chamber. We used HE staining to observe the morphology of lung tissue, and the changes in lung fibers were observed by Masson staining. The levels of inflammatory factors in mouse serum were detected by ELISA, and the levels of the oxidative stress indicators GSH, MDA, SOD and ROS were detected using commercially available kits. Moreover, a real-time qPCR assay was used to detect miR-212-5p expression, and Western blotting was used to detect the levels of SIRT6, HIF-1α and apoptosis-related proteins. CCK-8 was used to detect cell proliferation. Subsequently, we used flow cytometry to detect cell apoptosis. Dual-luciferase gene reporters determine the on-target binding relationship of miR-212-5p and SIRT6.

RESULTS:

SIRT6 was highly expressed in CIH-induced lung injury, as shown by bioinformatics analysis; however, miR-212-5p expression was decreased. Tempol promoted miR-212-5p expression, and the levels of SIRT6 and HIF-1α were inhibited. In BEAS-2B cells, Tempol also increased proliferation, inhibited apoptosis and inhibited oxidative stress in BEAS-2B cells under IH conditions. In BEAS-2B cells, these effects of Tempol were reversed after transfection with an miR-212-5p inhibitor. miR-212-5p targeted and negatively regulated the level of SIRT6 and overexpression of SIRT6 effectively reversed the enhanced influence of the miR-212-5p mimic on Tempol's antioxidant activity. Tempol effectively ameliorated lung injury in CIH mice and inhibited collagen deposition and inflammatory cell infiltration. Likewise, the therapeutic effect of Tempol could be effectively reversed by interference with the miR-212-5p inhibitor.

CONCLUSION:

Inhibition of the SIRT6-HIF-1α signaling pathway could promote the effect of Tempol by upregulating the level of miR-212-5p, thereby alleviating the occurrence of lung injury and providing a new underlying target for the treatment of lung injury.

2024-09-01·EUROPEAN JOURNAL OF NEUROSCIENCE

Chemerin in caudal division of nucleus tractus solitarius increases sympathetic activity and blood pressure

Article

作者: Wang, Jing‐Xiao ; Chen, Qi ; Chen, Jun‐Liu ; Hao, Wen‐Yuan ; Chen, Ai‐Dong ; Xu, Xiao‐Yu ; Li, Yue‐Hua ; Zhu, Guo‐Qing

Abstract:

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague–Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine‐like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin‐9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α‐NETA, superoxide scavenger tempol or N‐acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin‐9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin‐9 was inhibited by α‐NETA. The effects of cNTS microinjection of chemerin‐9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK‐801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin‐9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1‐mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin‐9‐induced responses.

项与 Tempol 相关的新闻（医药）

2024-10-24

·研发客

MNC投入逾百亿，海外AI制药势头有多猛？| AI

// • 2024年前三季度，跨国药企的AI相关合作交易数为21笔，总金额达到129.32亿美元； • 海外融资额超过1亿美元的AI制药企业在2024年上半年有6家； • 剂泰医药赖才达认为，国内AI制药公司的估值比较合理； • 英矽智能任峰认为，国内的AI技术基本可以比肩全球，但算法的优化和数据的积累稍显落后。拿下诺贝尔化学奖，仅仅是对AI的众多认可之一。“未来AI会是大势所趋，这已成为制药行业的共识，用AI的公司数量会超越不用的公司，慢慢实现产业界全面拥抱AI。”英矽智能联合首席执行官兼首席科学官任峰如是评价。事实上，跨国药企已开始拥抱AI技术。2023年，跨国药企的AI相关合作交易数仅为11笔。而2024年前三季度，这一交易数为21笔（见下图），总金额达到129.32亿美元。艾伯维更是以2.125亿美元收购了一家AI小分子公司Landos Biopharma，这也是跨国药企首次收购一家AI制药公司。跨国药企还建立内部AI团队。在今年诺贝尔化学奖公布的前一天，礼来任命了首任首席人工智能官（CAIO）这一新的职位，领导从药物发现、临床试验至制造等多个领域的AI 项目。此前8月，辉瑞也任命了首席AI官。在更早的2023年，赛诺菲宣布了“All in”人工智能战略，首席执行官Paul Hudson透露“赛诺菲在小分子药物发现的预测准确率超过80%，通过人工智能和机器学习化合物设计的小分子项目达到75%”。拓展阅读投资人如何看AI在医药行业的应用 MNC强势拥抱AI的同时，海外AI制药资本市场也正掀起热潮。2024年以来，大量的风险投资流入AI。如，超10亿美元融资的Xaira Therapeutics，创下今年以来生物医药领域的最高额融资，创始人团队里就有今年获得诺贝尔化学奖的David Baker教授。海外火热，国内呢？ 2024年上半年，海外融资额超过1亿美元的AI制药企业就有6家，其中不乏知名投资机构a16z、ARCH Venture Partners、红杉资本，以及礼来、安进、赛诺菲等MNC。其中Formation Bio在6月完成的3.72亿美元的D轮融资，就是由a16z领投，赛诺菲、红杉资本、Thrive Capital等跟投。正如BMS的首席数字与技术官Greg Meyers所说，“可能一些公司还没有很好的产品或技术平台契合市场，但只要GenAI（生成式人工智能）这个词出现在宣传平台中，就会融到钱。” 相比下，今年前三季度共有19家国内AI制药公司完成融资，其中披露融资额的14家企业，其总融资额约2.63亿美元。对此，剂泰医药联合创始人&CEO赖才达评论到，近期美国市场股价波动非常大，所以有一些泡沫的可能性，中国的资本市场相对冷静一些，估值也比较合理。的确，国内整体面临资本寒冬的情况下，AI制药领域同样难免遇到困难。不过也有好消息，晶泰科技于6月登录港交所挂牌上市，英矽智能在3月再一次向港交所递交招股书，拟香港主板IPO上市，剂泰医药完成了1亿美元的C轮融资。产品开发也有积极信息传出，9月，英矽智能的首个AI创新药物ISM001-055获得了临床2a期的积极结果。从技术端看，赖才达认为，国内外不存在太大差异，几乎是平行时间起步，可能海外的优势体现在与大药企的合作能够更快地推进内部管线和优化平台，而国内企业在出海时要花更多精力。任峰也表示，国内的AI技术基本可以比肩全球，但算法的优化和数据的积累稍显落后。“对AI制药公司而言，这两方面是主要壁垒。其一，目前企业大多使用的是公开数据，数据如何清洗并保证质量，这需要企业通过时间的积累和人员的培养积累达到。其二，算法需要不断经过项目验证，淘汰成功率低、优化成功率高的算法，才能提高最终由算法组合搭建产品的成功率。” 例如近期刚获得A轮融资的分子之心，创始人许锦波开创的深度学习算法RaptorX-Contact启发了后来的AlphaFold，被誉为“AI预测蛋白质结构第一人”。并购趋势初显新生代AI制药在资本市场火热的同时，初代AI制药企业已开始报团取暖。 8月，两家AI制药龙头公司Recursion和Exscientia宣布达成最终协议合并。两家公司都诞生于2013年最初的AI制药萌芽期，且在合并前Exscientia经历了不小的动荡。 5月Exscientia宣布裁员20%至25%，其CEO在2月被解雇，去年10月停止了一项核心产品EXS-21546的1/2期研究。 Recursion在合并前虽未有失败产品，但在合并一个月后的9月8日首次公布研究数据，主要药物REC-994的2期研究疗效有限，股价下跌超过16%。赖才达认为，AI制药行业正面临着产品进入后期阶段的瓶颈期，在资本市场中难免遇到困境，对Exscientia来说合并是当下合适的时机。不过Recursion背后有英伟达支持，并且Recursion和Exscientia的技术和管线并不重合，整合后能强强联合、优势互补。 “两家公司是生物学能力和化学能力的结合。”赖才达解释，“Recursion的强项是生物学能力，将蛋白组学、基因组学、表观组学的数据串联起来，理清靶点跟疾病的关系，Excientia强项在小分子结构设计，在知道一个靶点口袋后，设计出达到成药需求的小分子，且从药化角度解决传统制药的问题。结合后能打通制药环节的上下游，将高通量的上游细胞数据与下游的分子设计结合在一起，进一步梳理和整合两家的管线产品，节约研发与转化的成本。” 结合新生代AI企业Xaira来分析，赖才达认为利用AI技术解决研发流程中的某一关键问题、且是传统药物研发无法解决的问题，达到足够优势，成功的概率会更大一些。 “Xaira就是依托传统制药流程，在其中某一研发环节，AI能最大限度发挥作用，利用大模型解决抗体轻链端的设计，这是很大的突破点。而Excientia和Recursion在成立之初就想做全链条的AI制药研发，从而替代传统制药的流程。”赖才达说。 Xaira与Recursion、Excientia的不同选择路径，或许可以给全球AI制药行业的生物技术公司带来一些思考和借鉴。无论融资如何火热，最终获得市场认可仍需要产品来说话。英矽智能的TNIK抑制剂近期将临床研究推进到2期，这让我们增加了对AI制药的期待。下一篇，我们将关注那些可能最早冲线的在研产品。编辑 | 姚嘉 yao.jia@PharmaDJ.com 总第2229期访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

并购生物类似药

2024-09-24

·梅斯医学

每一口外卖、瓶装水都会让你脱发！中国学者最新：微塑料会损伤毛囊和皮肤，导致“秃头”，尤其是这种微塑料

随着塑料品的消费量逐年增加，塑料污染已然成为全球面临的最紧迫的环境威胁之一。而这些塑料制品释放出的塑料碎片，又会在物理、化学和生物的进一步降解后分解成为“更微小但更严重”的威胁，即「微塑料」。微塑料（Microplastic，MP），是指直径在1μm至5mm之间的塑料碎片和颗粒，在塑料制品使用过程中释放，特别是食物用途的塑料制品。事实上，越来越多的实验表明，塑料聚合物的碎裂并未止步于“微米级”，而是进一步形成了纳米塑料，数量上更是比预期高出了好几个量级。事实上，研究者早已在环境和生物体中发现了微/纳米塑料（MNPs）的存在。近年来，科学家在人类的肠胃、肺部以及胎盘等多个器官中发现了MNPs；去年，来自首都医科大学的研究学者竟在与外部环境没有接触的器官“心脏及其周围组织”中监测到MNPs，说明MNPs的污染已达到了人体最深的解剖结构。按照重量估计，每人每周大约吃掉5g微塑料，相当于一张银行卡的重量！还真是活到老，吃塑料到老。如果只是安静地在人体内待着，MNPs倒没什么可令人担心的。但真实情况下，这些侵入人体的MNPs大军很可能会影响人体健康，等待时机成熟的时候兴风作浪，造成多器官的损伤。微塑料在人体内的分布情况但一直以来，有个现象很少被关注到，那就是MPs的老化。由于紫外线、风以及众多物理和化学因素的影响，MPs在水生环境中很容易老化，导致其电荷、表面形态、疏水性、微观结构和环境行为等表面特征发生了改变。先前开展的研究表明，紫外线氧化可能会诱导MPs释放出破碎和氧化的化合物，导致细胞内产生更多的活性氧（ROS）。也就是说，老化的MPs会诱发更严重的氧化应激，进一步引起衰老、代谢紊乱以及其他疾病的发生。近日，中国研究团队最新发表的研究揭示了原生和老化MPs的又一大“罪证”——脱发和毛囊损伤！无论是体内还是体外实验中，研究者都观察到了“秃如其来”的变化。从机制上讲，原生MPs和老化MPs可通过氧化应激途径和抑制抗氧化相关蛋白来诱导紧密结合的损伤，进一步导致脱发的发生。正所谓“姜还是老的辣”，由于表面不规则性的增加和化学成分的改变，老化的MPs有着更强的毒性，能够加剧脱发。 https://doi.org/10.1016/j.envint.2024.108638 首先，研究者使用紫外线照射打造出老化的MPs，并测量了原始和老化MPs的物理和化学特性。先看物理特性的变化。原始MPs和老化MPs的平均水动力直径分别为120.10nm和116.21nm，两者几乎没有差别。但扫描电子显微镜（SEM）观察提示，老化MPs的表面特征发生了明显变化——MPs的表面光滑且呈球形，但老化MPs却出现了皱褶和裂纹。换言之，与原始MPs相比，老化MPs有着更大的表面积和空隙，并影响其吸收能力。当然，化学特性也有所改变。傅立叶变换红外吸收光谱仪（FTIR）分析表明，老化MPs中含氧官能团的峰值最大，同时变化也最显著。此外，STEM分析一致显示，O在碳颗粒内分布均匀，并在老化的MPs表面富集，促进ROS的生成。原生和老化MPs的理化特征紧接着，研究者在小鼠体内追踪了MPs的“行动轨迹”，发现摄入的MPs和老化的MPs会通过食道和胃，进一步穿过肠道屏障进入血液循环，最后沉积在毛囊组织中，尤其是集中在毛胚区域的细胞中。抵达了目的地之后，MPs要开始“兴风作浪”了。无论是原生MPs还是老化MPs，经其处理后的小鼠都出现了弥散性毛发稀疏。毛干组织的SEM观察则更能说明问题，不仅毛发数量有所减少，质量也变差了（变得乱蓬蓬的）。当然，这种情况在老化MPs组更为明显。具体来说，角质层状况分级系统提示，MPs处理后的毛发表面损伤从0级上升至1级，而老化MPs处理组则达到了2级。从毛囊整体数量上来看，老化MPs处理组小鼠的毛囊数量明显低于MPs组，可见老化MPs的威力更大，即会让小鼠变得更秃！老化MPs会诱导更严重的脱发正如先前提及的那样，从机制上来看，沉积在小鼠毛囊中的MPs和老化MPs，导致其中的ROS积累水平明显高于对照组，尤其是毛胚和真皮乳头部分。微塑料导致毛囊中ROS生成的增加，打破了细胞内ROS生成和消除之间的平衡，引起氧化应激的发生，这在老化MPs处理后更为严重。除了诱发氧化应激之外，MPs还能抑制抗凋亡蛋白的表达，并促进皮肤组织中的促凋亡蛋白和细胞的增殖，最终导致毛囊细胞的凋亡。毛囊无法进入再生阶段，新头发再难长出来，自然会越来越秃。此外，通过破坏毛囊中细胞之间紧密连接（TJs），MPs同样能加剧脱发。相反，当研究者使用Tempol清除了有害自由基并捕获了一氧化氮之后，逆转了MPs和老化MPs对毛囊的损伤效应，再一次证实了氧化应激是微塑料造成体内皮肤细胞凋亡和脱发的中间原因。最后，研究者还使用体外实验再一次验证了MPs以及老化MPs的毒性，包括增加氧化应激、抑制抗氧化相关蛋白活性，以及破坏细胞间紧密连接。 MPs加剧了皮肤和毛囊的氧化应激综上，微塑料居然还是“头发杀手”，能够导致毛发密度和形态的改变、破坏细胞间的紧密连接以及诱导氧化应激反应。具体来说，暴露于MPs以及老化MPs之下，大量的ROS累积并进一步诱导了氧化应激的发生，从而加剧毛囊凋亡，最终导致脱发。这篇研究最值得关注的点在于：老化MPs有着更强的细胞毒性。也就是说，聚苯乙烯在自然界存在的时间越长，经过更多的风吹雨打之后，细胞毒性作用也会更强。这种“老”塑料可能会给人体健康带去更大的损害，应引起人们的注意，也期待未来能有净化“老龄”微塑料的好办法。而对于普通人来说，我们能做的就是尽量减少生活中塑料制品的使用，以避免人类的五脏六腑都被塑料攻陷。参考资料： [1]Li Q, Jiang L, Feng J, Wang X, Wang X, Xu X, Chu W. Aged polystyrene microplastics exacerbate alopecia associated with tight junction injuries and apoptosis via oxidative stress pathway in skin. Environ Int. 2024 Apr;186:108638. doi: 10.1016/j.envint.2024.108638. Epub 2024 Apr 7. PMID: 38593689. 撰文 | Swagpp 编辑 | Swagpp ● 重磅！三明医改全覆盖下，年薪制分配细则来了！医生挣工分，最吃香科室大洗牌！该选哪个？口腔科自费项目多，冲到第一位！中医科也吃香了 ● Nature子刊最新：怀孕会导致大脑“萎缩”，且持续到产后！首次全程追踪的大脑变化图来了 ● 震惊！患者不满手术排到最后瞎起哄，知名网红医生吐槽：他患有梅毒，术前已跟他沟通，为啥总是刻意为难医生！都想第一个手术，顺序重要吗版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。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。点击下方「阅读原文」立刻下载梅斯医学APP！

2024-09-18

·Endpoints

With few efficacy details, Insilico claims a Phase 2a win in latest AI readout

Insilico Medicine reported Phase 2a results for its lead program, saying the study achieved its primary endpoint of safety and tolerability. But the efficacy data it released were much more vague. In a 71-patient trial testing ISM001-055 in idiopathic pulmonary fibrosis (IPF), Insilico said Wednesday that the drug improved a measurement of breathing called forced vital capacity compared to placebo after 12 weeks, and the responses were dose-dependent. However, Insilico did not report the absolute scores of each trial arm and whether the difference was statistically significant. In an interview Tuesday morning, Insilico CEO Alex Zhavoronkov declined to comment on the program’s statistical significance, saying he was not legally cleared to do so. He instead pointed to a trend identified by Insilico’s researchers across dosing arms as evidence the program works. “It depends on what kind of statistics you use,” Zhavoronkov said of ISM001-055’s statistical significance. “Currently, we don’t have enough patients to claim that it is statistically significant for approval, for example. But if you look at the data, it becomes very clear that there is a trend and there is a response.” If Insilico had run a longer trial specifically looking for efficacy, he said the dose response would have continued to increase. There’s no timeline yet for the program’s next steps, though Zhavoronkov said the company’s most immediate tasks are to submit the results to a medical journal and talk to regulators. ISM001-055 is a small molecule targeting TNIK, short for Traf2- and Nck-interacting kinase. Insilico said it discovered TNIK through its AI software and that inhibiting the target can halt or reverse fibrotic processes. Insilico is one of several biotechs aiming to speed up drug development through the use of artificial intelligence, and the readout comes a few weeks after Recursion — another AI player — also unveiled its first Phase 2 data. Some investors and VCs had framed the Recursion data drop as a “ moment of truth ” for the company and, by extension, the field after the first wave of AI-designed drugs fell short in the clinic . But Recursion’s data were too short on specifics for the public markets, and the startup’s stock price closed 16% lower the day it announced the data. In a rare neurological disease called cerebral cavernous malformations (CCM), Recursion’s drug, REC-994, succeeded on safety and tolerability endpoints but provided mixed results on efficacy. Recursion plans to advance the program, though it’s not yet clear if it will run a Phase 3 study or another Phase 2 trial. Zhavoronkov resisted comparing Insilico’s results to Recursion’s, citing both the differences in program design and diseases. He said IPF is a much more heterogeneous disease than CCM. While he said he respects Recursion and its CEO Chris Gibson, Zhavoronkov said people he spoke to were surprised the company didn’t terminate REC-994. “I don’t want to even compare with Recursion because it’s a different story,” Zhavoronkov said. “It’s not apples to apples. It’s like apples to seeds.”

临床2期临床结果

100 项与 Tempol 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Tempol	-	DB12449

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
放射性皮炎	临床3期	美国	Matrix Biomed, Inc.	2022-01-30
新型冠状病毒感染	临床3期	美国	DMK Pharmaceuticals Corp.	2021-09-01
中枢神经系统海绵状血管瘤	临床2期	美国	Recursion Pharmaceuticals, Inc.	2022-03-17
放射性口腔黏膜炎	临床2期	美国	Matrix Biomed, Inc.	2022-01-30
共济失调毛细血管扩张	临床2期	美国	Matrix Biomed, Inc.	2021-07-01
多形性胶质母细胞瘤	临床2期	美国	Matrix Biomed, Inc.	2021-06-01
非转移性前列腺癌	临床2期	美国	Matrix Biomed, Inc.	2021-05-30
复发性前列腺癌	临床2期	美国	Matrix Biomed, Inc.	2021-05-30
头颈部肿瘤	临床2期	美国	Matrix Biomed, Inc.	2019-05-13
粘膜炎	临床2期	美国	Matrix Biomed, Inc.	2019-05-13

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASN2014	N/A	interleukin-1 beta \| tumor necrosis factor alpha \| IL-6	-	Tempol	淵構衊衊艱齋廠獵遞製(廠襯製衊膚淵醖齋醖糧) = 廠衊積構壓餘願鑰獵製積獵膚顧築淵艱顧膚簾 (鑰願網網觸選鑰壓糧製 )	积极	2014-11-11
				Tempol	淵構衊衊艱齋廠獵遞製(廠襯製衊膚淵醖齋醖糧) = 窪衊衊鹽繭觸鏇艱膚鹽積獵膚顧築淵艱顧膚簾 (鑰願網網觸選鑰壓糧製 )
ARVO2013	N/A	毒性 superoxide dismutase \| oxidative stress	-	50 mM tempol	糧鹽蓋簾淵夢鹽簾鬱積(壓鹹範觸鏇顧鬱襯選遞) = 鏇艱築鏇簾選鏇遞襯鑰獵壓範選鹽顧糧廠窪憲 (糧鹹繭鑰齋願襯襯蓋網 )	积极	2013-06-01
ARVO2008	N/A	-	11	TEMPOL at 100mg/kg	衊廠繭醖淵醖淵憲網製(網壓構餘觸選淵憲鹹遞) = 鹽遞憲壓糧願顧觸廠艱廠獵憲蓋餘鹽築獵淵襯 (構窪憲鹹獵餘廠鏇範窪, 29) 更多	积极	2008-05-01
				Saline	衊廠繭醖淵醖淵憲網製(網壓構餘觸選淵憲鹹遞) = 獵願鏇壓築窪淵築獵簾廠獵憲蓋餘鹽築獵淵襯 (構窪憲鹹獵餘廠鏇範窪, 10) 更多