Reference - Detail
| RRC ID | 69557 |
|---|---|
| Author | Kohyama A, Kim MJ, Yokoyama R, Sun S, Omar AM, Phan ND, Meselhy MR, Tsuge K, Awale S, Matsuya Y. |
| Title | Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate. |
| Journal | Bioorg Med Chem |
| Abstract |
Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as "Austerity". As a part of a research program aiming to develop a new-generation of anticancer agents, known as "anti-austerity agents", guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC50 a value of 0.72 μM. It also inhibited pancreatic cancer cell migration and colony formation in a concentration-dependent manner. A mechanistic study revealed that this compound can inhibit the activation of the Akt/mTOR signaling pathway. Therefore, GSD-11 could be a promising lead compound for the anticancer drug discovery against pancreatic cancer. |
| Volume | 54 |
| Pages | 116563 |
| Published | 2022-1-15 |
| DOI | 10.1016/j.bmc.2021.116563 |
| PII | S0968-0896(21)00571-X |
| PMID | 34942553 |
| MeSH | Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Proliferation / drug effects Cell Survival / drug effects Dose-Response Relationship, Drug Drug Discovery* Drug Screening Assays, Antitumor Humans Molecular Structure Pancreatic Neoplasms / drug therapy* Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Pregnenediones / chemical synthesis Pregnenediones / chemistry Pregnenediones / pharmacology* Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism Signal Transduction / drug effects Structure-Activity Relationship TOR Serine-Threonine Kinases / antagonists & inhibitors TOR Serine-Threonine Kinases / metabolism Tumor Cells, Cultured |
| IF | 3.073 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | PANC-1(RCB2095) |