Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer.
Development of small-molecule inhibitors of the group I p21-activated kinases, emerging therapeutic targets in cancer.
复制标题
DOI：
10.1016/j.bcp.2010.03.012
复制
发表时间：
2010-09-01
影响因子：
5.8
通讯作者：
Kissil, Joseph L.
中科院分区：
文献类型：
--
作者：
Yi, Chunling;Maksimoska, Jasna;Marmorstein, Ronen;Kissil, Joseph L.
p21活化激酶（PAKs）是Rac/cdc42家族小g蛋白的直接下游效应物，是调节细胞行为的信号通路的关键介质，因此与包括癌症在内的病理状况有关。最近的研究证实了PAKs在乳腺癌和神经纤维瘤病中促进肿瘤发生的必要性。因此，人们对PAKs抑制剂的开发非常感兴趣，因为它可以作为生物标记物和治疗方法开发的先导物。虽然最初的方法是基于筛选竞争性有机抑制剂，但最近的努力集中在变构抑制剂，有机金属atp竞争性抑制剂的鉴定以及使用PAK1/抑制剂晶体结构进行抑制剂优化。这导致了高选择性和强效抑制剂的鉴定，这将作为进一步开发用于治疗应用的抑制剂的基础。
The p21-activated kinases (PAKs), immediate downstream effectors of the small G-proteins of the Rac/cdc42 family, are critical mediators of signaling pathways regulating cellular behaviors and as such, have been implicated in pathological conditions including cancer. Recent studies have validated the requirement for PAKs in promoting tumorigenesis in breast carcinoma and neurofibromatosis. Thus, there has been considerable interest in the development of inhibitors to the PAKs, as biological markers and leads for the development of therapeutics. While initial approaches were based on screening for competitive organic inhibitors, more recent efforts have focused on the identification of allosteric inhibitors, organometallic ATP-competitive inhibitors and the use of PAK1/inhibitor crystal structures for inhibitor optimization. This has led to the identification of highly selective and potent inhibitors, which will serve as a basis for further development of inhibitors for therapeutic applications.
登录
查看更多内容
影响因子：
5.3
作者：
Flaiz, Christine;Chernoff, Jonathan;Ammoun, Sylwia;Peterson, Jeffrey R.;Hanemann, Clemens O.
通讯作者：
Hanemann, Clemens O.
DOI：
10.1097/nen.0b013e318093e555
发表时间：
2007-07-01
影响因子：
3.2
作者：
Flaiz, Christine;Kaempchen, Katherine;Hanemann, Clemens Oliver
通讯作者：
Hanemann, Clemens Oliver
影响因子：
4.8
作者：
Jin, SH;Zhuo, Y;Field, J
通讯作者：
Field, J
影响因子：
4.8
作者：
Adam, L;Vadlamudi, R;Kumar, R
通讯作者：
Kumar, R
影响因子：
9.2
作者：
Chaudhary, A;King, WG;Brugge, JS
通讯作者：
Brugge, JS