Drug-development Strategy for Undruggable Targets Using a Novel Target Degradation Technology CANDDY

Abstract

Although the new era of precision medicine has come in Japan, the decease relating mutations without effective drugs are still remained. It is considered that the inhibitor development is not so easy for 75% of known decease relating proteins so-called “undruggable targets”. The protein degradation technology, which can induce ubiquitination of target protein, is expected to unlock undruggable targets, while it is still difficult because of the technological challenges included in current protein degradation technology. We have succeeded to induce degradation of the true undruggable targets KRAS G12D and G12V using originally developed chemical knockdown technology named CANDDY. In this report, we would outline the novel drug-development strategy for undruggable targets using CANDDY with an example of development of KRAS G12D/V degrader.