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更新于：2025-12-20

SKL2001

更新于：2025-12-20

概要

概要

基本信息

药物类型

小分子化药

别名

SKL2001

靶点

CTNNB x Wnt蛋白

作用方式

激动剂

作用机制

CTNNB 激动剂(Beta catenins agonists)、Wnt agonists

治疗领域-

在研适应症-

非在研适应症-

原研机构

Kookmin University

在研机构

SK Biopharmaceuticals Co., Ltd.

Kookmin University

非在研机构-

权益机构-

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/序列

分子式C14H14N4O3

InChIKeyPQXINDBPUDNMPE-UHFFFAOYSA-N

CAS号909089-13-0

关联

100 项与 SKL2001 相关的临床结果

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100 项与 SKL2001 相关的转化医学

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100 项与 SKL2001 相关的专利（医药）

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项与 SKL2001 相关的文献（医药）

2026-01-01·CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY

Esculin Facilitates Aerobic Glycolysis via the Wnt/β‐Catenin/ HIF ‐1α Pathway to Reduce the Progression of Gastric Cancer

Article

作者: Wang, Xiaolei ; Wang, Jing ; Wang, Haipeng ; Shang, Qing

ABSTRACT:

Background:

Gastric cancer (GC) is a complex pathogenesis closely related to various signalling pathways. Esculin, as a natural compound, possesses anti‐oxidation, anti‐inflammatory, and anti‐tumour influences, and has shown promising application prospects in research on colorectal cancer (CRC) and others. However, the specific impact of Esculin on GC remains unclear. This article explores the action mechanism of Esculin in gastric cancer, which not only helps to understand its anti‐cancer properties but may also offer novel approaches and strategies for treating GC.

Methods:

Using the CCK‐8 method to screen the concentration of Esculin that does not affect the viability of normal gastric mucosal cells GES‐1. At this concentration, the changes in viability, proliferation level, migration ability, invasion ability, and apoptosis level of HGC‐27 and AGS were measured. The levels of related proteins were detected through Western blot. Subsequent use of the glycolysis inhibitor 3‐BrPA, the Wnt signalling pathway activator SKL2001, and the inhibitor LiCl interfered with GC cells. The impact of Esculin on aerobic glycolysis in cells was assessed by measuring glucose uptake levels, pyruvate production levels, lactate generation levels, ATP production levels, and extracellular acidification rate (ECAR). The regulatory effect of Esculin on the Wnt/β‐catenin/HIF‐1α pathway was evaluated through immunofluorescence and Western blot. Injecting HGC‐27 cells to build a xenograft tumour model and evaluating the effect of Esculin gavage on tumour growth in mice.

Results:

Esculin at concentrations of 0, 20, 40, and 80 μM is non‐toxic to GES‐1. An increase in the concentration of Esculin correlates with a continuous decline in the viability of four GC cell lines, with GC cells showing the highest significance. The levels of proliferation, migration, and invasion in both cell lines significantly decrease with increasing concentrations of Esculin, while the apoptosis rate significantly increases. 80 μM of Esculin can significantly inhibit glucose absorption, pyruvate production, lactate, and ATP generation in cells, leading to a significant decrease in ECAR; at the same time, it significantly inhibits the expression of proteins in the Wnt/β‐catenin/HIF‐1α signalling pathway. Administering 20 mg/kg of Esculin by gavage can significantly suppress tumour growth in mice, concurrently leading to a reduction of proteins associated with the Wnt/β‐catenin/HIF‐1α pathway within the tumour tissue.

Conclusion:

Esculin inhibits aerobic glycolysis in cells via the Wnt/β‐catenin/HIF‐1α pathway, alleviating the progress of GC.

2025-11-01·MOLECULAR BIOTECHNOLOGY

Retraction Note: Ethanol Extract of Anacyclus pyrethrum Root Ameliorates Cough-Variant Asthma Through the TLR4/NF-κB Pathway and Wnt/β-Catenin Pathway

Article

作者: Jin, Xiaoyue ; Yang, Hao ; Zhang, Rui ; Yibulayimu, Nadire ; Zheng, Jun ; Liu, Changjiang

Cough-variant asthma (CVA) has been recognized as the initial stage or pre-asthmatic state of classic asthma, which characterized by cough as the primary clin. presentation.Inhaled glucocorticoids, oral leukotriene receptor antagonists and antihistamines are the clin. treatments, but their efficacy is not satisfactory.Some traditional Chinese medicine (TCM) has been reported to have certain advantages in the treatment of CVA, but the underlying mol. mechanisms are still unclear.Recent research has indicated that Anacyclus pyerhrurm (L) DC. is commonly used in the treatment of human diseases.The aim of our study was to evaluate the anti-inflammatory and anti-oxidative mechanism of the ethanol extract of Anacyclus pyrethrum (L) DC. root (EEAP) in a model of CVA.In our study, we indicated that EEAP ameliorated CVA by reducing cough frequency and inflammatory effect and oxidative stress in an in vivo rat model of CVA.In addition, EEAP ameliorated LPS-induced cell apoptosis and regulated inflammatory effect and oxidative stress in vitro.Mechanistically, EEAP exerted anti-inflammatory effects through regulating the TLR4/NF-κB pathway and Wnt/β-catenin pathway, and overexpressing TLR4 or activating the Wnt/β-catenin pathway by SKL2001 reversed EEAP-exerted effects in LPS-exposed BEAS-2B and 16-HBE cells.In conclusion, EEAP attenuated cell apoptosis, inflammation and oxidative stress through restraining the TLR4/NF-κB pathway and Wnt/β-catenin pathway in CVA, which shown that EEAP might be a promising therapeutic agent for CVA and may provide a theor. basis for clin. treatment with CVA patients.

2025-11-01·Circulation-Arrhythmia and Electrophysiology

CKAP4 Promotes Atrial Fibrosis and Enhances Atrial Fibrillation Vulnerability via WNT/β-Catenin Activation

Article

作者: Gao, Yanhua ; Chen, Zhisong ; Liu, Xuebo ; Feng, Yuntao ; Tan, Hongwei

BACKGROUND::

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, characterized by atrial fibrosis, a crucial substrate facilitating its initiation and persistence. CKAP4 (cytoskeleton-associated protein 4) has been associated with fibroblast activation; however, its involvement in atrial remodeling and AF susceptibility remains unclear.

METHODS::

We measured serum CKAP4 by ELISA in 189 patients with drug-refractory AF and 79 controls and then correlated these levels with left atrial scar burden assessed by 3-dimensional electroanatomic mapping. CKAP4 cell-type specificity and AF-associated regulation were evaluated in human single-cell/single-nucleus RNA-seq data sets (GSE238242 and GSE224959). CKAP4 regulation and function were examined in mice subjected to transverse aortic constriction or Ang II (angiotensin II) infusion and in neonatal rat atrial fibroblasts stimulated with Ang II using CKAP4 knockdown/overexpression. AF inducibility was tested by transesophageal burst pacing. Mechanistic studies assessed CKAP4 interactions with wingless/INT signaling pathway (WNT) 3A/WNT5A (co-immunoprecipitation and proximity ligation) and perturbed β-catenin signaling with an agonist (Wnt/β-catenin pathway agonist) or inhibitor (β-catenin/TCF pathway inhibitor) in vitro and in vivo.

RESULTS::

Serum CKAP4 was higher in AF than controls ( P <0.001) and correlated with regional and total scar burden (r=0.16–0.29; all P <0.05). CKAP4 was enriched in fibroblasts and upregulated in AF in both human data sets. Transverse aortic constriction and Ang II increased atrial CKAP4 in vivo. In atrial fibroblasts, CKAP4 knockdown reduced α-Smooth Muscle Actin (α-SMA), collagen I/III, vimentin, and migration, whereas overexpression produced opposite effects. In mice, CKAP4 knockdown attenuated left atrial fibrosis and reduced AF inducibility. CKAP4 interacted with WNT3A and WNT5A and activated β-catenin signaling; SKL2001 rescued the antifibrotic/antiarrhythmic effects of CKAP4 knockdown, while β-catenin/TCF pathway inhibitor blunted CKAP4-overexpression–induced collagen synthesis and migration.

CONCLUSIONS::

CKAP4 promotes atrial fibrosis and increases AF vulnerability through the WNT/β-catenin signaling pathway, highlighting the CKAP4–WNT/β-catenin axis as a promising therapeutic target to attenuate atrial structural remodeling in AF.

项与 SKL2001 相关的新闻（医药）

2025-08-20

·生物谷

中药不玄乎！Phytomedicine揭秘｜独活寄生汤通过外泌体调控关键轴，抑制髓核细胞铁死亡，缓解椎间盘退变

腰腿痛是困扰许多人的常见问题，而椎间盘退变（IVDD）是导致这类脊柱疾病的主要原因，其核心特征是髓核细胞（NPC）减少和细胞外基质（ECM）降解。作为一种经典中药方剂，独活寄生汤（DHJSD）在缓解IVDD方面的疗效已得到临床认可，但具体作用机制尚未完全阐明。近日，发表于Phytomedicine的一项研究Duhuo Jisheng decoction alleviates intervertebral disc degeneration by inhibiting nucleus pulposus cell ferroptosis via the exosome-mediated miR-19b-3p/ACSL4 axis，深入揭示了独活寄生汤通过外泌体介导的miR-19b-3p/ACSL4轴抑制髓核细胞铁死亡，从而缓解椎间盘退变的分子机制，为IVDD的治疗提供了新的思路。研究首先通过生物信息学分析和RT-qPCR检测发现，miR-19b-3p在IVDD患者的髓核组织中表达显著下调。同时，高效液相色谱（HPLC）分析明确了独活寄生汤中的20种活性成分，这些成分来源于其包含的15味中药。随后，研究人员从经不同浓度（5.4、10.8、21.6 g/kg）独活寄生汤含药血清处理的人骨髓间充质干细胞（hBMSCs）中分离出外泌体（EXOs），并通过透射电镜、纳米颗粒追踪分析和Western blotting对其进行表征，发现这些外泌体具有典型的杯状双层膜结构，且10.8 g/kg剂量组的外泌体表面标志物CD9、CD63、CD81和TSG101表达最高，被hNPCs的摄取效率也最强，故后续实验选用该浓度组外泌体（DHJSD-EXO）。图 1：独活寄生汤的HPLC指纹图谱在体外实验中，用白细胞介素-1β（IL-1β）构建hNPCs退变模型后，DHJSD-EXO处理显著增强了hNPCs的增殖能力，抑制了细胞凋亡，改善了线粒体功能，减少了脂质过氧化产物丙二醛（MDA）的积累，同时上调了铁死亡相关蛋白GPX4的表达，下调了ACSL4的表达。在ECM代谢方面，DHJSD-EXO增加了胶原蛋白II和聚集蛋白聚糖等合成代谢标志物的表达，减少了基质金属蛋白酶13（MMP13）和ADAMTS5等分解代谢标志物的表达，免疫荧光结果也证实了这一点。图 2：独活寄生汤来源外泌体减轻白细胞介素-1β诱导的人髓核细胞铁死亡和细胞外基质降解进一步机制研究显示，DHJSD-EXO中富含miR-19b-3p，且miR-19b-3p可直接靶向ACSL4的3'非翻译区（UTR）。功能获得与缺失实验表明，过表达miR-19b-3p的DHJSD-EXO能更显著地抑制铁死亡和ECM降解，而敲低miR-19b-3p则逆转了这些保护作用。此外，DHJSD-EXO还通过miR-19b-3p抑制了Wnt/β-catenin信号通路，激活了Hippo信号通路，减少了β-catenin和YAP的核转位，当使用Wnt/β-catenin通路激活剂SKL2001时，DHJSD-EXO对铁死亡的抑制作用被削弱。图 3：独活寄生汤来源外泌体中的miR-19b-3p通过靶向ACSL4抑制人髓核细胞铁死亡在大鼠IVDD模型中，于术后1周和5周椎间盘内注射DHJSD-EXO，9周后通过磁共振成像（MRI）和组织学评估发现，DHJSD-EXO处理显著降低了椎间盘退变的Pfirrmann分级和组织学评分，改善了椎间盘结构，增加了髓核区域，同时上调了miR-19b-3p和胶原蛋白II的表达，下调了ACSL4的表达，且10.8 g/kg剂量组的效果优于5.4 g/kg剂量组。图 4：独活寄生汤来源外泌体减轻大鼠椎间盘退变并在体内抑制ACSL4表达图 5：实验验证机制示意图综上所述，这项研究表明，独活寄生汤可促进hBMSCs分泌富含miR-19b-3p的外泌体，这些外泌体被hNPCs摄取后，通过靶向抑制ACSL4，同时调控Wnt/β-catenin和Hippo信号通路，有效抑制髓核细胞铁死亡和ECM降解，从而缓解椎间盘退变。这一发现不仅为理解独活寄生汤治疗IVDD的机制提供了新视角，也为中医药通过“中药-外泌体-靶基因”调控网络干预退行性疾病奠定了理论和实验基础，有望为临床治疗IVDD提供新的靶点和策略。参考文献： Feng J, Miao H, Xiao Z, et al. Duhuo Jisheng decoction alleviates intervertebral disc degeneration by inhibiting nucleus pulposus cell ferroptosis via the exosome-mediated miR-19b-3p/ACSL4 axis. Phytomedicine. Published online July 30, 2025. doi:10.1016/j.phymed.2025.157113 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

临床研究临床结果

100 项与 SKL2001 相关的药物交易

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