論文 - 詳細
| RRC ID | 58881 |
|---|---|
| 著者 | Kuramoto K, Yamada H, Shin T, Sawada Y, Azami H, Yamada T, Nagashima T, Ohnuki K. |
| タイトル | Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer. |
| 巻・号 | 28(5) |
| ページ | 115307 |
| 公開日 | 2020-3-1 |
| DOI | 10.1016/j.bmc.2020.115307 |
| PII | S0968-0896(19)32001-2 |
| PMID | 32007387 |
| MeSH | AMP-Activated Protein Kinases / metabolism* Administration, Oral Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Dose-Response Relationship, Drug Drug Development* Drug Screening Assays, Antitumor Humans Male Mice Mice, Nude Molecular Structure Protein Kinase Inhibitors / administration & dosage Protein Kinase Inhibitors / chemistry Protein Kinase Inhibitors / pharmacology* Rats Rats, Sprague-Dawley Structure-Activity Relationship |
| IF | 3.073 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OCUB-M(RCB0881) |