| K-ras mutations can be frequently found in various cancers and are associated with resistance to treatment or poor prognosis. Thus far, however, there is no effective agent for treatment of cancers with k- ras mutations. This study was designed to identify small molecular inhibitors which may selectively target G13D mutant k-ras. The potentially active enamine analog compounds (n=520), having high toxicity (>55%) in the HCT 116 colon carcinoma cell lines, were screened in 293 HEK cells expressing the k-ras-lac-Z fusion protein in the control vector pcDNA3.1/Hygro/lac-Z or pcDNA3.1/Hygro/lac-Z+k-ras mutant, or pcDNA3.1/Hygro/lac-Z+k-raswild-type . The data indicated that there is no specific binding site between the compounds and k-ras because either the wild-type and mutated k-ras both could not be inhibited, or the wild-type and mutated k-ras were both inhibited with synchronously impacting the non-k-ras transfected 293 HEK cells by the potential active enamine analog compounds. Therefore, further studies and modifications on the structures and conformation of the active compounds are necessary in order to identify the ideal inhibitors for G13D mutant k- ras. |
