8 results on '"Hang Yin Chu"'
Search Results
2. Drug Discovery of DKK1 Inhibitors
- Author
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Hewen Jiang, Zongkang Zhang, Yuanyuan Yu, Hang Yin Chu, Sifan Yu, Shanshan Yao, Ge Zhang, and Bao-Ting Zhang
- Subjects
drug discovery ,wnt signaling ,DKK1 inhibitors ,antibodies ,small molecule inhibitors ,nucleic acid inhibitors ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Dickkopf-1 (DKK1) is a well-characterized Wnt inhibitor and component of the Wnt/β-catenin signaling pathway, whose dysregulation is associated with multiple abnormal pathologies including osteoporosis, Alzheimer’s disease, diabetes, and various cancers. The Wnt signaling pathway has fundamental roles in cell fate determination, cell proliferation, and survival; thus, its mis-regulation can lead to disease. Although DKK1 is involved in other signaling pathways, including the β-catenin-independent Wnt pathway and the DKK1/CKAP4 pathway, the inhibition of DKK1 to propagate Wnt/β-catenin signals has been validated as an effective way to treat related diseases. In fact, strategies for developing DKK1 inhibitors have produced encouraging clinical results in different pathological models, and many publications provide detailed information about these inhibitors, which include small molecules, antibodies, and nucleic acids, and may function at the protein or mRNA level. However, no systematic review has yet provided an overview of the various aspects of their development and prospects. Therefore, we review the DKK1 inhibitors currently available or under study and provide an outlook on future studies involving DKK1 and drug discovery.
- Published
- 2022
- Full Text
- View/download PDF
3. Dickkopf-1: A Promising Target for Cancer Immunotherapy
- Author
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Hang Yin Chu, Zihao Chen, Luyao Wang, Zong-Kang Zhang, Xinhuan Tan, Shuangshuang Liu, Bao-Ting Zhang, Aiping Lu, Yuanyuan Yu, and Ge Zhang
- Subjects
DKK1 ,cancer ,Wnt signaling pathway ,immunotherapy ,immune surveillance ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.
- Published
- 2021
- Full Text
- View/download PDF
4. Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery
- Author
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Zihao Chen, Ning Zhang, Hang Yin Chu, Yuanyuan Yu, Zong-Kang Zhang, Ge Zhang, and Bao-Ting Zhang
- Subjects
CTGF ,fibrosis ,aptamers ,anti-CTGF ,domain structure ,CCN2 ,Biology (General) ,QH301-705.5 - Abstract
Connective tissue growth factor (CTGF) is a key signaling and regulatory molecule involved in different biological processes, such as cell proliferation, angiogenesis, and wound healing, as well as multiple pathologies, such as tumor development and tissue fibrosis. Although the underlying mechanisms of CTGF remain incompletely understood, a commonly accepted theory is that the interactions between different protein domains in CTGF and other various regulatory proteins and ligands contribute to its variety of functions. Here, we highlight the structure of each domain of CTGF and its biology functions in physiological conditions. We further summarized main diseases that are deeply influenced by CTGF domains and the potential targets of these diseases. Finally, we address the advantages and disadvantages of current drugs targeting CTGF and provide the perspective for the drug discovery of the next generation of CTGF inhibitors based on aptamers.
- Published
- 2020
- Full Text
- View/download PDF
5. Cathepsin K: The Action in and Beyond Bone
- Author
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Rongchen Dai, Zeting Wu, Hang Yin Chu, Jun Lu, Aiping Lyu, Jin Liu, and Ge Zhang
- Subjects
Cathepsin K ,osteoclast ,bone resorption ,osteoporosis ,osteoarthritis ,Cathepsin K inhibitor ,Biology (General) ,QH301-705.5 - Abstract
Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.
- Published
- 2020
- Full Text
- View/download PDF
6. Therapeutic aptamer targeting sclerostin loop3 for promoting bone formation without increasing cardiovascular risk in osteogenesis imperfecta mice
- Author
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Luyao Wang, Yuanyuan Yu, Shuaijian Ni, Dijie Li, Jin Liu, Duoli Xie, Hang Yin Chu, Qing Ren, Chuanxin Zhong, Ning Zhang, Nanxi Li, Meiheng Sun, Zong-Kang Zhang, Zhenjian Zhuo, Huarui Zhang, Shu Zhang, Mei Li, Weibo Xia, Zhenlin Zhang, Lin Chen, Peng Shang, Xiaohua Pan, Aiping Lu, Bao-Ting Zhang, and Ge Zhang
- Subjects
Disease Models, Animal ,Mice ,Apolipoproteins E ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Osteogenesis ,Risk Factors ,Oligonucleotides ,Animals ,Medicine (miscellaneous) ,Osteogenesis Imperfecta ,Atherosclerosis ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Published
- 2022
7. Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery
- Author
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Ning Zhang, Yuanyuan Yu, Bao-Ting Zhang, Hang Yin Chu, Ge Zhang, Zihao Chen, and Zong-Kang Zhang
- Subjects
0301 basic medicine ,Angiogenesis ,medicine.medical_treatment ,Protein domain ,aptamers ,Connective tissue ,Review ,Biology ,anti-CTGF ,03 medical and health sciences ,Cell and Developmental Biology ,0302 clinical medicine ,Fibrosis ,domain structure ,medicine ,lcsh:QH301-705.5 ,integumentary system ,Drug discovery ,Growth factor ,fibrosis ,CTGF ,Cell Biology ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Wound healing ,CCN2 ,Developmental Biology - Abstract
Connective tissue growth factor (CTGF) is a key signaling and regulatory molecule involved in different biological processes, such as cell proliferation, angiogenesis, and wound healing, as well as multiple pathologies, such as tumor development and tissue fibrosis. Although the underlying mechanisms of CTGF remain incompletely understood, a commonly accepted theory is that the interactions between different protein domains in CTGF and other various regulatory proteins and ligands contribute to its variety of functions. Here, we highlight the structure of each domain of CTGF and its biology functions in physiological conditions. We further summarized main diseases that are deeply influenced by CTGF domains and the potential targets of these diseases. Finally, we address the advantages and disadvantages of current drugs targeting CTGF and provide the perspective for the drug discovery of the next generation of CTGF inhibitors based on aptamers.
- Published
- 2020
8. Cathepsin K: The Action in and Beyond Bone
- Author
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Ge Zhang, Jun Lu, Jin Liu, Zeting Wu, Hang Yin Chu, Aiping Lyu, and Rongchen Dai
- Subjects
0301 basic medicine ,Proteases ,Cathepsin K ,Osteoporosis ,Review ,Pharmacology ,Bone resorption ,Cell and Developmental Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Osteoclast ,medicine ,In patient ,lcsh:QH301-705.5 ,Cathepsin K inhibitor ,business.industry ,lung fibrosis ,Cell Biology ,medicine.disease ,osteoporosis ,cardiovascular diseases ,osteoarthritis ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,chemistry ,Drug development ,030220 oncology & carcinogenesis ,osteoclast ,business ,bone resorption ,Odanacatib ,Developmental Biology - Abstract
Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.
- Published
- 2020
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