Discovery of small-molecule Ras inhibitors that display antitumor activity by interfering with Ras·GTP-effector interaction [0.03%]
发现一类小分子Ras抑制剂：通过干扰具有GTP酶活性的Ras与效应因子的相互作用而发挥抗肿瘤活性
Fumi Shima,Yoko Yoshikawa,Shigeyuki Matsumoto et al.
Fumi Shima et al.
Ras proteins, particularly their active GTP-bound forms (Ras·GTP), were thought "undruggable" owing to the absence of apparent drug-accepting pockets in their crystal structures. Only recently, such pockets have been found in the crystal s...
Fuyuhiko Tamanoi
Fuyuhiko Tamanoi
Yoel Kloog,Galit Elad-Sfadia,Roni Haklai et al.
Yoel Kloog et al.
The Ras inhibitor S-trans,trans-farnesylthiosalicylic acid (FTS, Salirasib®) interferes with Ras membrane interactions that are crucial for Ras-dependent signaling and cellular transformation. FTS had been successfully evaluated in clinica...
Kwang-Jin Cho,Dharini van der Hoeven,John F Hancock
Kwang-Jin Cho
Oncogenic mutant K-Ras is highly prevalent in multiple human tumors. Despite significant efforts to directly target Ras activity, no K-Ras-specific inhibitors have been developed and taken into the clinic. Since Ras proteins must be anchore...
A two-hybrid approach to identify inhibitors of the RAS-RAF interaction [0.03%]
一种鉴定RAS-Raf相互作用抑制剂的双杂交方法
Vladimir Khazak,Susanne Eyrisch,Juran Kato et al.
Vladimir Khazak et al.
MCP compounds were developed with the idea to inhibit RAS/RAF interaction. They were identified by carrying out high-throughput screens of chemical compounds for their ability to inhibit RAS/RAF interaction in the yeast two-hybrid assay. A ...
Inhibitors of the ROCK serine/threonine kinases: key effectors of the RhoA small GTPase [0.03%]
RhoA小G蛋白效应物ROCK丝/苏氨酸激酶抑制剂的研究进展
Dominico Vigil,Channing J Der
Dominico Vigil
Aberrant activation of the RhoA small GTPase has been implicated in cancer and other human diseases. Therefore, inhibitors of RhoA may have important therapeutic value. However, similar to the Ras small GTPases, RhoA itself is not considere...
Targeting the Dbl and dock-family RhoGEFs: a yeast-based assay to identify cell-active inhibitors of Rho-controlled pathways [0.03%]
针对Dbl和dock家族Rho交换因子的一种酵母型筛选方法以识别控制Rho通路的细胞活性抑制剂
Anne Blangy,Philippe Fort
Anne Blangy
The Ras-like superfamily of low molecular weight GTPases is made of five major families (Arf/Sar, Rab, Ran, Ras, and Rho), highly conserved across evolution. This is in keeping with their roles in basic cellular functions (endo/exocytosis, ...
Aptamer-derived peptide inhibitors of Rho guanine nucleotide exchange factors [0.03%]
来源于适配体的Rho鸟苷酸交换因子抑制肽
Susanne Schmidt,Anne Debant
Susanne Schmidt
Small G proteins of the Rho family and their activators the guanine nucleotide exchange factors (RhoGEFs) regulate essential cellular functions and their deregulation has been associated with an amazing variety of human disorders, including...
Suranganie Dharmawardhane,Eliud Hernandez,Cornelis Vlaar
Suranganie Dharmawardhane
The Rac inhibitor EHop-016 was developed as a compound with the potential to inhibit cancer metastasis. Inhibition of the first step of metastasis, migration, is an important strategy for metastasis prevention. The small GTPase Rac acts as ...
Sugar-based inhibitors of Ras activation: biological activity and identification of Ras-inhibitor binding interface [0.03%]
基于糖的抑制Ras激活抑制剂：生物活性及识别Ras-抑制剂结合界面
Alessandro Di Domizio,Francesco Peri
Alessandro Di Domizio
Inhibition of oncogenic Ras activation through small molecules is a promising approach to the pharmacologic treatment of human tumors. A common strategy to block Ras activation and signal transduction is based on molecules that interfere wi...