Biyu Yang

Shanghai Institute of Materia Medica

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Tao Meng

Henan University of Technology

Hangtian Yue

Shanghai Institute of Materia Medica

Zuoquan Xie

Chinese Academy of Sciences

Qingzhong Zeng

Shanghai Institute of Materia Medica

Lanping Ma

Chinese Academy of Sciences

Deqiang Zhang

Shanghai Institute of Materia Medica

Xiyuan Wang

Shanghai Institute of Materia Medica

Han Li

Nanjing Second Hospital

Meiyu Geng

Chinese Academy of Sciences

Xiyuan Li

Chinese Academy of Sciences

Cooperative Institutions

Chinese Academy of Sciences

Shanghai Institute of Materia Medica

University of Chinese Academy of Sciences

Fudan University

ShanghaiTech University

Central South University

Hunan University of Arts and Science

Sun Yat-sen University

Chinese Academy of Medical Sciences & Peking Union Medical College

Shanghai Jiao Tong University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Visible-light-promoted organic-dye-catalyzed sulfonylation/cyclization to access indolo[2,1-a]isoquinoline derivatives

Organic & Biomolecular Chemistry (2023)

Yucai Tang Jinglin Duan Biyu Yang Yu‐Peng He Changyuan Du

An efficient visible-light-promoted organic-dye-catalyzed radical cascade cyclization was developed for the rapid synthesis of sulfonyl-substituted indolo[2,1-a]isoquinolines and benzimidazo[2,1-a]isoquinolin-6(5H)-ones. Using the economical and environmentally benign Eosin B as the photocatalyst, a wide range of indolo[2,1-a]isoquinoline derivatives were obtained in moderate to good yields. Mechanistic studies indicate that a sulfonyl radical pathway is involved in this reaction. Compared with previous works, this protocol has the advantages of being metal- and base-free, using visible light as a traceless energy source, simple operation and mild reaction conditions, all of which make this methodology more attractive.

Isoquinoline

Sulfonyl

Eosin Y

Visible spectrum

10.1039/d3ob01289a

Cite

Citations (4)

Development of ASGR-Mediated Hepatocyte-Targeting Cytotoxic Drug Conjugates with CTSB-Cleavable Linkers Incorporating Succinimide and Succinic Acid Monoamide

Journal of Medicinal Chemistry (2025)

Jingsheng Jiang S Jian Feifei Lin Zhuo Zhang Qianqian Shen

The ASGR-mediated endocytosis has been successfully applied to the hepatocyte-targeted delivery of therapeutic oligonucleotides via glycoconjugates. However, few studies have explored the conjugated small molecules due to the challenge of cleaving suitable linkers for the release of active small molecules, which is especially different from GalNAc-ONs cleaved by the deoxyribonuclease II in the lysosome. In this study, GalNAc-MMAE conjugates linked by CTSB-cleavable linkers were designed and synthesized. A comprehensive approach revealed that the conjugates were endocytosed by ASGR and subsequently hydrolyzed by CTSB, releasing MMAE. The optimized conjugate with a succinic acid monoamide as the fragment of the linker demonstrated favorable plasma stability, excellent biodistribution, and significant antitumor activities in vivo with weight gain at the effective dose in an orthotopic hepatocellular carcinoma mouse model. This research provides a strategy for developing anti-HCC therapeutic agents using GalNAc drug conjugates with CTSB-cleavable linkers to release active small molecules.

Succinimides

Conjugate

Succinic acid

10.1021/acs.jmedchem.4c02232

Cite

Citations (0)

Visible-Light-Induced Cascade Azidation/Cyclization of Activated Alkenes to Synthesize Azidated Indolo[2,1-a]isoquinolines

Chinese Journal of Organic Chemistry (2024)

Yucai Tang Yu‐Peng He Biyu Yang Jinglin Duan Changyuan Du

10.6023/cjoc202401034

Cite

Citations (1)

Data from A DXd/TLR7-Agonist Dual-Conjugate Anti-HER2 ADC Exerts Robust Antitumor Activity Through Tumor Cell Killing and Immune Activation

Hangtian Yue Hui Xu Lanping Ma Xiyuan Li Biyu Yang

<div>AbstractThe emergence of trastuzumab deruxtecan (T-DXd), a new-generation antibody–drug conjugate (ADC), has profoundly altered the therapeutic paradigm for HER2-positive solid tumors, demonstrating remarkable clinical benefits. However, the combined outcomes of T-DXd with immunotherapy agents remain ambiguous. In this study, we introduce Tras-DXd-MTL1, an innovative HER2 targeting ADC that integrates the topoisomerase inhibitor DXd and a toll like receptor 7 (TLR7) agonist MTT5, linked to trastuzumab via a GGFG tetrapeptide linker. Mechanistically, Tras-DXd-MTL1 retains the DNA-damaging and cell-killing properties of topoisomerase inhibitors while simultaneously enhancing the immune response within the tumor microenvironment. This is achieved by promoting immune cell infiltration and activating dendritic cells and CD8+T cells via MTT5. In vivo evaluation of Tras-DXd-MTL1’s antitumor potency revealed a notably superior performance compared with the T-DXd (Tras-DXd) or Tras-MTL1 in immunocompetent mice with trastuzumab-resistant EMT6-HER2 tumor and immunodeficient mice with JIMT-1 tumor. This improved efficacy is primarily attributed to its dual functions of immune stimulation and cytotoxicity. Our findings highlight the potential of incorporating immunostimulatory agents into ADC design to potentiate antitumor effects and establish durable immune memory, thereby reducing tumor recurrence risks. Therefore, our study offers a novel strategy for the design of immune-activating ADCs and provides a potential approach for targeting solid tumors with different levels of HER2 expression.</div>

Conjugate

TLR7

10.1158/1535-7163.c.7522921

Cite

Citations (0)

Organic-Dye-Catalyzed Visible-Light-Mediated Alkoxycarbon-ylation of 2-Aryl-N-acryloyl Indoles with Carbazates

Chinese Journal of Organic Chemistry (2023)

Changyuan Du Yucai Tang Jinglin Duan Biyu Yang Yu‐Peng He

10.6023/cjoc202305024

Cite

Citations (3)

Figure S3 from A DXd/TLR7-Agonist Dual-Conjugate Anti-HER2 ADC Exerts Robust Antitumor Activity Through Tumor Cell Killing and Immune Activation

Hangtian Yue Hui Xu Lanping Ma Xiyuan Li Biyu Yang

Figure S3. Expression of CD40+DCs in PBMC. PBMC was treated with gradient concentrations of R848 and MTT-6 for 24 h, and the expression level of CD40 in DC cells (CD11b+CD11c+) was measured by flow cytometry, shown as the representative images.

Conjugate

TLR7

10.1158/1535-7163.27602011

Cite

Citations (0)

Figure S5 from A DXd/TLR7-Agonist Dual-Conjugate Anti-HER2 ADC Exerts Robust Antitumor Activity Through Tumor Cell Killing and Immune Activation

Hangtian Yue Hui Xu Lanping Ma Xiyuan Li Biyu Yang

Figure S5. Tumor weight and flow cytometry analysis of tumor infiltrating leukocytes in EMT6-HER2 tumor model. (A) Tumor weight of Fig. 5A. (B-D) Gating strategy for flow cytometry analysis of immune subset in tumor samples. (E-H) EMT6-HER2 tumor were treated with control (0.9%NaCl), trastuzumab (1 mg/kg), Tras-DXd (1 mg/kg), or Tras-DXd-MTL1 (1 mg/kg) for 2 days (n=5), and immune subsets in tumor tissue were analyzed by flow cytometry, and the proportion macrophages (E), CD86+ macrophages (F), CD206+ macrophages (G), and CD3+T cells (H) were shown. The data were shown as mean ± SEM, One-way ANOVA (A, E-G) with Tukey’s correction were used for multiple comparisons. ns, not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Conjugate

TLR7

10.1158/1535-7163.27602005

Cite

Citations (0)

Amlodipine inhibits Synaptotagmin-4’s oncogenic activity on gastric cancer proliferation by targeting calcium signaling

Functional & Integrative Genomics (2024)

Wen Huang Shuo Yang Minying Deng Rongkui Luo Huaiyu Liang

Abstract Background: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. Purpose: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. Methods: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. Results: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca 2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. Conclusion: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca 2+ -dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.

Amlodipine

10.1007/s10142-024-01345-8

Cite

Citations (1)

CuCl-Catalyzed Cyanoalkylation/Cyclization to Construct Indolo[2,1-a]isoquinoline Derivatives

Russian Journal of Organic Chemistry (2023)

Yucai Tang Qian Zhou Yiting Yang Biyu Yang Jinglin Duan

Isoquinoline

10.1134/s1070428023120151

Cite

Citations (0)

Figure S2 from A DXd/TLR7-Agonist Dual-Conjugate Anti-HER2 ADC Exerts Robust Antitumor Activity Through Tumor Cell Killing and Immune Activation

Hangtian Yue Hui Xu Lanping Ma Xiyuan Li Biyu Yang

Figure S2. HEK293T-luci cells expressing the NF-κB reporter system were treated with TNF-α (40 ng/ml), MTT-5 (10 µM), R848 (10 µM) and control (0.1%DMSO) for 24 h. The data were shown as mean ± SEM, and one-way ANOVA was used for multiple comparisons. ns, not significant, ****P < 0.0001.

Conjugate

TLR7

10.1158/1535-7163.27602014

Cite

Citations (0)