The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Yueyin Pan - One of the best experts on this subject based on the ideXlab platform.
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Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2.
The journal of physical chemistry letters, 2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease (Mpro) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of Mpro. We further searched for low-molecular-weight drugs containing niacin or hit 1 pharmacophores with enhanced inhibiting activity, e.g., Carmofur, bendamustine, triclabendazole, emedastine, and omeprazole, in which omeprazole is the only one binding to the C-terminal domain of SARS-CoV-2 Mpro. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
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Repurposing low–molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2
2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified Carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
Hiroshi Takagi - One of the best experts on this subject based on the ideXlab platform.
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an individual patient data meta analysis of long supported adjuvant chemotherapy with oral Carmofur in patients with curatively resected colorectal cancer
Oncology Reports, 2001Co-Authors: Junichi Sakamoto, Susumu Kodaira, Chikuma Hamada, Katsuki Ito, Yoshihiko Maehara, Hiroshi Takagi, Keizo Sugimachi, Hiroaki Nakazato, Yasuo OhashiAbstract:To reappraise the benefits of the long supported chemotherapy with Carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for Carmofur; and a highly significant advantage for Carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral Carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.
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oral adjuvant chemotherapy with Carmofur hcfu for colorectal cancer five year follow up tokai hcfu study group third study on colorectal cancer
Journal of Surgical Oncology, 1996Co-Authors: Katsuki Ito, Akihiro Yamaguchi, Kaoru Miura, Tomoyuki Kato, Shozo Baba, Sumio Matsumoto, Masataka Ishii, Hiroshi TakagiAbstract:Background A joint study was performed by the Tokai HCFU study group, which included seven institutions, to examine the value of oral administration of Carmofur (HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection. Methods The patients were divided into two groups, a control group receiving no HCFU and a group administered HCFU for 1 year, using a centralized registration system by telephone. Among 173 patients entered into this study, 159 evaluable cases were analyzed for evaluation of the drug. Results The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group. In particular, the rate was much higher in patients with colon cancer. No severe side effects arose from adjuvant chemotherapy with HCFU. Conclusion Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment. © 1996 Wiley-Liss, Inc.
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prospective adjuvant therapy with mitomycin c and Carmofur hcfu for colorectal cancer 10 year follow up tokai hcfu study group the first study for colorectal cancer
Journal of Surgical Oncology, 1996Co-Authors: Katsuki Ito, Akihiro Yamaguchi, Kaoru Miura, Tomoyuki Kato, Akihiko Koike, Hiroshi TakagiAbstract:A joint study was performed by the Tokai HCFU study group, which included 41 institutions to study the usefulness of the concomitant therapy with Mitomycin C (MMC) and Carmofur (HCFU) as a postoperative adjuvant chemotherapy in patients with colorectal cancer who had curative resection. Patients were divided into two groups, Group MMC and Group MMC+HCFU, using the "envelope" method. Among the 172 patients who had the envelope opened, 149 evaluable cases were analyzed for evaluation of the drug. The cumulative 10-year survival rates of Group MMC+HCFU had a statistically significant increase in survival rate compared with Group MMC. In particular, the rate was statistically significant in patients with colorectal cancer who had lymph node invasion. There were no severe side effects due to the adjuvant chemotherapy with MMC+HCFU. Thus the adjuvant chemotherapy with MMC+HCFU is suggested to be a useful and safe postoperative adjuvant chemotherapy.
Jia Gao - One of the best experts on this subject based on the ideXlab platform.
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Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2.
The journal of physical chemistry letters, 2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease (Mpro) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of Mpro. We further searched for low-molecular-weight drugs containing niacin or hit 1 pharmacophores with enhanced inhibiting activity, e.g., Carmofur, bendamustine, triclabendazole, emedastine, and omeprazole, in which omeprazole is the only one binding to the C-terminal domain of SARS-CoV-2 Mpro. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
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Repurposing low–molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2
2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified Carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
Katsuki Ito - One of the best experts on this subject based on the ideXlab platform.
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an individual patient data meta analysis of adjuvant therapy with Carmofur in patients with curatively resected colon cancer
Japanese Journal of Clinical Oncology, 2005Co-Authors: Junichi Sakamoto, Susumu Kodaira, Chikuma Hamada, Katsuki Ito, Hiroaki Nakazato, Yasuo Ohashi, Mahbubur Rahman, Masayuki YasutomiAbstract:BACKGROUND: Oral Carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard. METHODS: We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of oral Carmofur for curatively resected colon cancer in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, Carmofur as adjuvant chemotherapy compared with surgery-alone, 5 years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in Carmofur and surgery-alone group. Oral Carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95% confidence interval (CI) = 0.68-0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95% CI = 0.65-0.91; P = 0.003). CONCLUSIONS: This individual patient-based meta-analysis demonstrated that oral Carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers.
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An Individual Patient Data Meta-analysis of Adjuvant Therapy with Carmofur in Patients with Curatively Resected Colon Cancer
2005Co-Authors: Junichi Sakamoto, Susumu Kodaira, Chikuma Hamada, Katsuki Ito, Hiroaki Nakazato, Yasuo Ohashi, Mahbubur Rahman, Masayuki YasutomiAbstract:Background: Oral Carmofur, either as a single or in combination with other chemotherapeutic agents, has been used as adjuvant chemotherapy for curatively resected colon cancer patients. Past trialsandmeta-analyses indicate that it is somewhateffective inextendingsurvival of patients with this cancer. The objective of this study was to perform a reappraisal of randomized clinical trials conducted in this regard. Methods: We designed an individual patient-based meta-analysis of relevant clinical trials to examine thebenefit oforal Carmofur for curatively resectedcoloncancer in termsofoverall survival (OS) and disease-free survival (DFS). Results: We analyzed individual patient data of three randomized clinical trials, which met the predetermined inclusion criteria. These three trials had a combined total of 2152 patients, Carmofurasadjuvantchemotherapycomparedwithsurgery-alone, 5years follow-up, intention-to-treat-based analytic strategy and similar end points (OS and DFS). In a pooled analysis, 5 year OS rates were 80.4 and 76.4%, and 5 year DFS rates 76.9 and 71.0%, respectively, in Carmofur and surgery-alone group. Oral Carmofur had significant advantage over surgery-alone in terms of both OS [pooled hazard ratio, 0.82; 95 % confidence interval (CI) = 0.68–0.99; P = 0.043] and DFS (pooled hazard ratio, 0.77; 95 % CI = 0.65–0.91; P = 0.003). Conclusions: This individual patient-based meta-analysis demonstrated that oral Carmofur significantly improves both OS and DFS in patients with curatively resected colon cancers. Key words: colorectal cancer – Carmofur – chemotherapy – disease-free survival – overall survival – randomized clinical trial
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an individual patient data meta analysis of long supported adjuvant chemotherapy with oral Carmofur in patients with curatively resected colorectal cancer
Oncology Reports, 2001Co-Authors: Junichi Sakamoto, Susumu Kodaira, Chikuma Hamada, Katsuki Ito, Yoshihiko Maehara, Hiroshi Takagi, Keizo Sugimachi, Hiroaki Nakazato, Yasuo OhashiAbstract:To reappraise the benefits of the long supported chemotherapy with Carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for Carmofur; and a highly significant advantage for Carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral Carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.
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oral adjuvant chemotherapy with Carmofur hcfu for colorectal cancer five year follow up tokai hcfu study group third study on colorectal cancer
Journal of Surgical Oncology, 1996Co-Authors: Katsuki Ito, Akihiro Yamaguchi, Kaoru Miura, Tomoyuki Kato, Shozo Baba, Sumio Matsumoto, Masataka Ishii, Hiroshi TakagiAbstract:Background A joint study was performed by the Tokai HCFU study group, which included seven institutions, to examine the value of oral administration of Carmofur (HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection. Methods The patients were divided into two groups, a control group receiving no HCFU and a group administered HCFU for 1 year, using a centralized registration system by telephone. Among 173 patients entered into this study, 159 evaluable cases were analyzed for evaluation of the drug. Results The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group. In particular, the rate was much higher in patients with colon cancer. No severe side effects arose from adjuvant chemotherapy with HCFU. Conclusion Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment. © 1996 Wiley-Liss, Inc.
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prospective adjuvant therapy with mitomycin c and Carmofur hcfu for colorectal cancer 10 year follow up tokai hcfu study group the first study for colorectal cancer
Journal of Surgical Oncology, 1996Co-Authors: Katsuki Ito, Akihiro Yamaguchi, Kaoru Miura, Tomoyuki Kato, Akihiko Koike, Hiroshi TakagiAbstract:A joint study was performed by the Tokai HCFU study group, which included 41 institutions to study the usefulness of the concomitant therapy with Mitomycin C (MMC) and Carmofur (HCFU) as a postoperative adjuvant chemotherapy in patients with colorectal cancer who had curative resection. Patients were divided into two groups, Group MMC and Group MMC+HCFU, using the "envelope" method. Among the 172 patients who had the envelope opened, 149 evaluable cases were analyzed for evaluation of the drug. The cumulative 10-year survival rates of Group MMC+HCFU had a statistically significant increase in survival rate compared with Group MMC. In particular, the rate was statistically significant in patients with colorectal cancer who had lymph node invasion. There were no severe side effects due to the adjuvant chemotherapy with MMC+HCFU. Thus the adjuvant chemotherapy with MMC+HCFU is suggested to be a useful and safe postoperative adjuvant chemotherapy.
Jiahai Zhang - One of the best experts on this subject based on the ideXlab platform.
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Repurposing Low-Molecular-Weight Drugs against the Main Protease of Severe Acute Respiratory Syndrome Coronavirus 2.
The journal of physical chemistry letters, 2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease (Mpro) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of Mpro. We further searched for low-molecular-weight drugs containing niacin or hit 1 pharmacophores with enhanced inhibiting activity, e.g., Carmofur, bendamustine, triclabendazole, emedastine, and omeprazole, in which omeprazole is the only one binding to the C-terminal domain of SARS-CoV-2 Mpro. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.
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Repurposing low–molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2
2020Co-Authors: Jia Gao, Liang Zhang, Xiaodan Liu, Zhongliang Zhu, Jiahai Zhang, Yunyu Shi, Yueyin PanAbstract:The coronavirus disease (COVID-19) pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. Drug repurposing is a feasible method for emergency treatment. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease of the SARS-CoV-2 (Mpro), thereby modestly inhibiting the enzymatic activity of Mpro. Chemical shift perturbations induced by niacin and hit 1 indicate a partial overlap of their binding sites, i.e., the catalytic pocket of Mpro may accommodate derivatives with large molecular sizes. Therefore, we searched for drugs containing niacin or hit 1 pharmacophores and identified Carmofur, bendamustine, triclabendazole, and emedastine; these drugs are highly capable of inhibiting protease activity. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.