Aldo-keto reductase 1C3 (AKR1C3) is known to be a cancer biomarker correlated to androgen synthesis, and causes drug resistance by direct action on chemotherapeutics and by stabilizing AR splice variant 7 (ARv7). While selective inhibitors against AKR1C3 are developed, the ARv7 is thought to be undruggable. Here, the authors develop an AKR1C3-ARv7 dual PROTAC degrader based on a selective inhibitor against AKR1C3, showing the potential for degradation of AKR1C3 and ARv7 simultaneously.
- Angelica V. Carmona
- Shirisha Jonnalagadda
- Paul C. Trippier