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更新于：2025-09-27

SKL2001

更新于：2025-09-27

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）

2025-11-01·CELLULAR SIGNALLING

SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling

Article

作者: He, Feinan ; Tong, Weifang ; Huang, Baishuo ; Li, Jinqiu ; Wang, Hongyan ; Teng, Bo ; Wang, Sanchun

BACKGROUND:

Serpin peptidase inhibitor clade H member 1 (SERPINH1) is implicated in collagen processing and tumor progression, yet its role in laryngeal squamous cell carcinoma (LSCC) remains unclear. This study aimed to elucidate the clinical significance and molecular mechanism of SERPINH1 in LSCC.

METHODS:

Multi-cohort bioinformatics analysis (TCGA, GEO) identified SERPINH1 as a prognostic marker. SERPINH1 expression was validated in LSCC tissues (IHC, immunofluorescence, Western blot). Functional assays (CCK-8, EdU, Transwell) and xenograft models assessed malignant behaviors. Transcriptomics and co-IP/LC-MS revealed downstream pathways and interactors. Wnt agonist (SKL2001) rescue experiments confirmed pathway dependency.

RESULTS:

SERPINH1 was overexpressed in LSCC tissues versus adjacent normal and predicted poor survival. SERPINH1 knockdown suppressed proliferation, migration/invasion, and tumor growth in vitro and in vivo. Mechanistically, SERPINH1 bound COL7A1 to stabilize the Wnt/β-catenin signaling complex, reducing β-catenin phosphorylation and enhancing nuclear translocation. Wnt activation via SKL2001 rescued SERPINH1-knockdown phenotypes.

CONCLUSION:

SERPINH1 drives LSCC progression via COL7A1-mediated Wnt/β-catenin signaling activation. Targeting this axis may offer novel therapeutic strategies for LSCC.

2025-09-30·FASEB JOURNAL

Human Umbilical Cord Mesenchymal Stem Cells Reduce Renal Tubular Epithelial Cell Apoptosis by Regulating the Wnt/β‐Catenin Pathway in Diabetic Nephropathy

Article

作者: Tian, Na ; Bai, Xiaoying ; Guan, Yucan ; Yang, Huan ; Nie, Ping ; Nie, Weichen

ABSTRACT:

Diabetic nephropathy (DN), a leading cause of kidney failure, involves early renal tubular epithelial cell (TEC) apoptosis. This study investigated whether human umbilical cord‐derived mesenchymal stem cells (hUCMSCs) protect against DN‐related TEC apoptosis by modulating the Wnt/β‐catenin signaling pathway. A Type 2 diabetic rat model was established using a high‐fat diet and streptozotocin injection. hUCMSCs were administered intravenously. In vitro, HK11 cells were treated with high glucose and palmitate (HG/P), with or without hUCMSCs and the Wnt/β‐catenin agonist SKL2001. Apoptosis, mitochondrial function, and oxidative stress were assessed by Annexin V‐FITC/PI, JC‐1, ROS staining, and Western blotting. Pathway activation was evaluated by immunoblotting, immunohistochemistry, and immunofluorescence. hUCMSCs alleviated renal tubular injury and reduced TEC apoptosis in diabetic rats. In vitro, hUCMSCs mitigated HG/P‐induced ROS accumulation, mitochondrial dysfunction, and apoptosis, accompanied by upregulation of Bcl‐2 and downregulation of Bax and cleaved caspase‐3. Mechanistically, hUCMSCs suppressed HG/P‐induced activation of Wnt/β‐catenin signaling, as evidenced by decreased β‐catenin nuclear accumulation and reduced Wnt5a expression, together with restoration of p‐GSK3β levels. Co‐treatment with the Wnt/β‐catenin agonist SKL2001 reversed these molecular changes and partially attenuated the anti‐apoptotic effects of hUCMSCs. hUCMSCs protect TECs from HG/P‐induced apoptosis by inhibiting the Wnt/β‐catenin pathway.

2025-07-01·PHYTOMEDICINE

18β-Glycyrrhetinic acid from Glycyrrhiza Uralensis protects colonic epithelium in ulcerative colitis by activating Wnt/β-catenin pathway to restore tight junction

Article

作者: Zhang, Bo ; Qiu, Yi ; Liu, Tao ; Yang, Yang ; Dong, Shi ; Shu, Gang ; Zhong, Rao ; Peng, Xi ; Huang, Shiyuan

BACKGROUND:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Glycyrrhiza uralensis extract (ULE), a traditional medicinal plant extract, is globally recognized for its anti-inflammatory and gastrointestinal therapeutic effects. However, the precise mechanisms underlying the therapeutic benefits of ULE in UC management remain poorly understood.

PURPOSE:

This study aimed to elucidate the pharmacological effects of ULE and its primary active constituent, 18β-glycyrrhetinic acid (18β-GA), on the colonic epithelium in UC rat models.

STUDY DESIGN AND METHODS:

We employed a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and a TNBS-LPS-induced UC Caco-2 cell model to explore the protective mechanisms of ULE and 18β-GA. The methodologies included UPLC-Q/TOF-MS chemical analysis in chemico, network pharmacological screening in silico, histopathological and flow cytometry evaluations in vivo, and molecular biological validation in vitro.

RESULTS:

ULE significantly alleviated UC symptoms in rats, including weight loss, diarrhea, and rectal bleeding, particularly at a dosage of 100 mg/kg. Network pharmacology and transcriptomic analyses identified the Wnt pathway as a pivotal hub linking inflammation, epithelial proliferation, and tight junction integrity. ULE treatment reduced apoptosis (from 13.24% to 8.34%), CD3⁺ T cells (from 13% to 6.04%), and CD45RA⁺ B cells (from 7.23% to 1.67%) in colonic tissues. Furthermore, ULE restored tight junction protein expression, notably increasing Occludin (2.5×) and ZO-1 (5.3×). Similarly, 18β-GA activated the Wnt/β-catenin signaling pathway and elevated tight junction protein expression, thereby protecting against UC-like damage in the Caco-2 cell model. These protective effects were potentiated by the Wnt pathway agonist SKL2001 and diminished by the antagonist IWR-1.

CONCLUSION:

ULE and its active constituent, 18β-GA, exhibit protective effects against TNBS-induced colonic epithelial injury and tight junction protein disruption by upregulating the Wnt/β-catenin signaling pathway, making them promising therapeutic candidates for UC management.

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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