| 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
|
| リソース情報 |
| ヒト・動物細胞 |
OCUB-M(RCB0881) |
