The study is designed as a single Group, Dose Elevating trial which evaluates safety to confirm the final maximum tolerated dose by the combination of oral administration of SH003 to docetaxel administered patients.
Firstly, 3 subjects is recruited and administered for 21 days for the starting dose of 2,400 mg / day. If no DLT occurs, raise the dose to a secondary dose of 3,600 mg / day. If DLT occurs, additional 3 subjects are recruited and administered for 2,400mg / day. After, If two or more of the six subjects shows DLT, stop the capacity increase, whereas if DLT occurs in less than 1 person, increase the dose to 3,600 mg / day. Next, 3 subjects is recruited and administered for 21 days for a dose of 3,600 mg / day. If no DLT occurs, raise the dose to 4,800 mg / day. If DLT occurs, 3 subjects are additionally recruited and administered for 3,600 mg / day. After, If two or more of the six subjects shows DLT, stop the capacity increase, whereas if DLT occurs in less than 1 person, increase the dose to 4,800 mg / day. Finally, 3 subjects is recruited and administered for a dose of 4,800 mg / day. If no DLT occurs, complete the study. If DLT occurs, additional 3 subjects are recruited and administered for 4,800mg / day and complete the study after observation.

开始日期2020-06-01

申办/合作机构

Kyunghee University Medical Center

100 项与 SH003 相关的临床结果

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100 项与 SH003 相关的转化医学

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100 项与 SH003 相关的专利（医药）

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项与 SH003 相关的文献（医药）

2025-05-01·ANTICANCER RESEARCH

SH003 Inhibits Proliferation and Induces Apoptosis in NSCLC Cell Lines by Inhibiting the Receptor Tyrosine Kinase-related Pathway

Article

作者: Je, Jeong-Hui ; Cho, Sung-Gook ; Kim, Tae Hun ; Lee, Hyeong-Chan ; Yoo, Ji-Sung ; Ko, Seong-Gyu ; Cho, Kwang-Jin ; Sim, Yun-Beom ; Hwang, Hyun-Ha ; Kim, Taehyoun

BACKGROUND/AIM:

SH003, a novel herbal mixture consisting of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, has shown promising anti-cancer effects in various cancers, including non-small cell lung cancer (NSCLC), which comprises approximately 85% of all lung cancer cases. Characterized by high mortality rates due to late-stage diagnosis and frequent development of resistance to traditional therapies, NSCLC is a significant clinical challenge. This study investigated the anti-cancer effects of SH003 on NSCLC cells, focusing on its role in modulating receptor tyrosine kinase (RTK) signaling pathways.

MATERIALS AND METHODS:

NSCLC cell lines (A549, H460, HCC827) were treated with SH003 to evaluate cell viability (MTT assay), colony formation, apoptosis (Annexin V/7-AAD staining, western blot), and cell cycle distribution (PI staining). Phosphorylation of RTKs and related signaling molecules was analyzed using a phospho-RTK array and western blot. In vivo anti-tumor effects were assessed using an A549 xenograft mouse model treated orally with SH003.

RESULTS:

NSCLC cell lines A549, H460, and HCC827 treated with SH003 showed significant, dose-dependent cell viability and colony formation reductions. SH003 induced apoptosis, evidenced by increased cleaved PARP and caspase-8 levels, and caused G₁/S cell cycle arrest. Additionally, SH003 treatment decreased phosphorylation of multiple receptor tyrosine kinases (RTKs), including ErbB4, FGFR1, FGFR3, and PDGFRβ, as confirmed by an RTK array. In an A549 xenograft mouse model, SH003 inhibited tumor growth without affecting body weight, indicating low systemic toxicity.

CONCLUSION:

SH003 is a promising multi-target therapeutic agent for NSCLC, offering a novel strategy to improve patient outcomes.

2025-05-01·ANTICANCER RESEARCH

SH003 Inhibits Proliferation and Induces Apoptosis in Colon Cancer Through the RTK-STAT3 Pathway

Article

作者: Je, Jeong-Hui ; Yoo, Ji-Sung ; Lee, Hyeong-Chan ; Kim, Tae Hun ; Ko, Seong-Gyu ; Cho, Sung-Gook ; Sim, Yun-Beom ; Cho, Kwang-Jin ; Hwang, Hyun-Ha ; Cheon, Chunhoo

BACKGROUND/AIM:

Colon cancer is the most prevalent type of gastrointestinal cancer, characterized by high incidence and mortality rates despite advancements in diagnosis and treatment. Although chemotherapy is the standard treatment for advanced cases, survival benefits are often limited, highlighting the need for innovative therapeutic strategies. SH003, an herbal mixture composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, has demonstrated anticancer properties across various cancer types. This study aimed to explore the anticancer effects of SH003 on colon cancer through in vitro and in vivo experiments.

MATERIALS AND METHODS:

In vitro studies were conducted using human colon cancer cell lines, including HCT116, HT29, SW480, SW620, LoVo, LS174T, H508, and LS1034. Cell viability assays were performed to determine IC₅₀ values over time. Apoptosis induction was assessed through Western blot analysis. Cell cycle progression was analyzed by examining the expression of cell cycle-related proteins. The disruption of the RTK-STAT3 signaling pathway was evaluated by measuring the phosphorylation of ALK using RTK-array. In vivo experiments involved establishing an HCT116 xenograft mouse model to assess tumor growth inhibition and systemic toxicity following SH003 administration.

RESULTS:

SH003 significantly reduced cell viability in all tested colon cancer cell lines, with IC₅₀ values decreasing over time, indicating a time-dependent cytotoxic effect. Apoptosis induction was confirmed by increased levels of cleaved PARP, caspase-3, caspase-8, and caspase-9. SH003 also induced G₁/S phase cell cycle arrest, as evidenced by decreased expression of p-Rb, CDK2, CDK4, and Cyclin D1. Furthermore, SH003 disrupted the RTK-STAT3 signaling pathway by reducing ALK phosphorylation and decreasing the levels of p-STAT3, c-Myc, and cyclin D1. In vivo, SH003 significantly suppressed tumor growth in the HCT116 xenograft mouse model, reducing tumor volumes without causing notable systemic toxicity.

CONCLUSION:

These findings suggest that SH003 possesses robust anticancer effects against colon cancer by inducing apoptosis, causing cell cycle arrest, and disrupting RTK-STAT3 signaling. The in vivo results further confirm SH003's efficacy and safety, supporting its potential as a promising therapeutic option for colon cancer treatment. Further studies are warranted to elucidate its mechanisms and clinical applicability.

2025-01-01·ONCOLOGY RESEARCH

Anticancer effects of SH003 and its active component Cucurbitacin D on oral cancer cell lines via modulation of EMT and cell viability

Article

作者: Choi, Hyeong Sim ; Yun, Pil-Young ; Ku, Jeong-Kui ; Ko, Seong-Gyu

Background:

Oral cancer remains a significant global health challenge, as it has high morbidity and mortality rates. Current treatments show limited efficacy and have severe side effects, prompting searches for new therapeutic agents. SH003, a traditional herbal formulation comprising Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, has demonstrated potential anticancer properties in previous studies. However, its specific efficacy against oral cancer and the role of its key components, particularly Cucurbitacin D, remain underexplored.

Methods:

The cytotoxic effects of SH003 and its major components-i.e., Cucurbitacin D, Decursin, Formononetin, and Nodakenin-were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), Trypan Blue exclusion, and Lactate Dehydrogenase (LDH) release assays. Cell migration was analyzed via wound healing assays, and apoptosis induction was assessed using cell cycle analysis and caspase activation assays. Epithelial-to-mesenchymal transition (EMT) marker expression (E-cadherin and N-cadherin) was measured using Western blotting and Quantitative reverse transcription PCR (qRT-PCR).

Results:

SH003 significantly reduced cell viability in a dose-dependent manner, with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells. Of the individual compounds, Cucurbitacin D was identified as a key active agent, as it exhibited potent inhibition of cell migration and significant modulation of EMT markers, including the upregulation of E-cadherin and downregulation of N-cadherin. These effects were most pronounced in YD-9 cells.

Conclusions:

Taken together, these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003, particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells. This study provides valuable insight into the mechanistic basis of SH003, highlighting its potential as a therapeutic agent against oral cancer. Further research, including in vivo studies and clinical trials, is needed to elucidate its precise mechanisms and potential applications against other cancer types.

100 项与 SH003 相关的药物交易

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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
乳腺癌	临床1期	-	Kyunghee University Medical Center	2020-06-01
肺癌	临床1期	-	Kyunghee University Medical Center	2020-06-01
实体瘤	临床1期	美国	Kyunghee University Medical Center	2017-03-29