| 查看: 672 | 回复: 0 | |||
letterman新虫 (小有名气)
|
[交流]
Current drug target for Prostate Cancer
|
|
[Content] In this series, each posting will include the current or emerging drug targets for one type of cancer. [Intended audience] Students and researchers who are interested in anticancer drug discovery. Topic 1: Current drug targets and emerging drug targets for prostate cancer Prostate cancer is critically depending on the signaling of androgen receptor (AR). Current major drug target for advanced prostate cancer is the AR. There are three domains in the AR: i) The N-terminal domain (NTD); ii) DNA-binding domain (DBD); and iii) Ligand-binding domain (LBD). When the hormone (DHT) binds with AR that the LBD, the AR signaling is activated. Thus, the current strategy to inhibit the AR signaling is to develop compounds to bind with AR at the LBD (to prevent the binding of DHT with AR). Such compounds are referred to as anti-androgen and a number of such compounds have been developed into drugs, including bicalutamide and enzalutamide. However, during the treatment of anti-androgen, despite of initial response, the patients almost always become resistance to the treatment and the AR signaling is reactivated (despite of the anti-androgen treatment). While there are many possible mechanisms have been proposed, there are two key mechanisms: First, the emergence of AR splice variants that do not have the LBD confer resistance to the LBD-targeting antiandrogens. It is important to note that all of the current clinically used antiandrogens are designed to target the AR LBD; Second, the mutation in the AR LBD could confer resistance to antiandrogens. Worse yet, some mutations at the LBD could lead to the AR mutants that are activated by antiandrogensuch as enzalutamide. How to develop potent and selective inhibitors of the AR splice variants is a burning issue in the field. One approach is to target the AR NTD, but this is very challenging. The major reason is that the AR NTD is intrinsically disorder. No crystal structure of the AR NTD is available. Nevertheless, the 3rd generation of antiandrogens could be the compounds that target the AR NTD. |
回复此楼» 猜你喜欢
庆祝再次获得国家基金资助，希望大家好运，厚积薄发总会中标的！
已经有111人回复
-
大家帮忙看看这个函评分数是怎样的？
已经有36人回复
-
药理学论文润色/翻译怎么收费?
已经有148人回复
-
安徽医科大学-药理学求博导
已经有1人回复
-
求购时间长一些的硝酸钍
已经有0人回复
-
广西医科大学基础医学院自身免疫病课题组招收基础医学、药学和生物学等专业的研究生
已经有7人回复
-
[学习资料分享] FAERS数据库的不良反应挖掘(频数法/贝叶斯法)
已经有1人回复
-
招收医学、基础医学类调剂研究生
已经有0人回复
-
是否属于脾肾阳虚证
已经有0人回复