Development of antitumor agents targeting for prenoid-metabolizing enzymes

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Increment of prenylated small G proteins is a possible cause of abnormal growth and metastasis of carcinomas. Here, we found a novel metabolic pathway of prenoids and identified three human prenylaldehyde reductases as enzymes that involves the pathway. The enzymes highly express in a variety of carcinomas and have been suggested to be promoted to cancer cell proliferation. We succeeded development of the inhibitors that show potent and selective inhibitory effect against each enzymes by structure-based drug design. Moreover, the inhibitors significantly suppressed proliferation of cancer cells. Therefore, prenylaldehyde reductases are novel tumor-targeting molecules and their selective inhibitors are expected to be novel anticancer drugs.