| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
|
|---|
| Outline of Final Research Achievements |
Novel FK228 analogs as PI3K/HDAC dual inhibitors were synthesized, and, by docking simulation of a new analog and PI3K catalytic subunit p100α, and an evaluation of the PI3K inhibitory activity, we synthesized new analog FK-A11 which was stronger PI3K inhibitory activity than FK228 and its analog FK-A5. We found that the novel FK228 analogs with the strong PI3K inhibitory activity had inhibitory activities on both the apoptotic induction and intracellular signal transduction and strongly suggested that the PI3K inhibitory activity correlated with antitumor effect of the compounds. We also found that the novel FK228 analog was effective against prostate cancer and colorectal cancer, particularly effective in colorectal cancer cells with the KRAS gene mutation refractory to anti-EGFR antibody, a molecular target drug. Also, we found that FK-A11 was a pan-PI3K inhibitor and an ATP-competitive inhibitor.
|
