Proteolysis-targeting chimeras (PROTACs) were first reported by Kathleen Sakamoto, Craig Crews, and Raymond Deshaies in 2001. A chimeric molecule consisting of ovalicin (a MetAP-2 small molecule inhibitor) and IκBα phosphopeptide (a recruiter of the SCFβ-TRCP E3 ligase complex) separated by a linker was constructed and shown to induce MetAP-2 degradation in in vitro cell models. Further study confirmed that E3 ligase-mediated ubiquitination and subsequent proteasome degradation was responsible for reduced MetAP-2 levels. Continued work on this system by Craig Crews and others has expanded the potential pool of E3 ligases and degradation targets with Arvinas Inc. founded in 2013 to bring PROTAC drugs to market. As of April 2023, Arvinas has one drug in Stage 3 clinical trials (ARV-471, an estrogen receptor degrader), and two drugs in Stage 2 clinical trials (androgen receptor degraders ARV-110 and ARV-766) for treatment of breast and prostate cancer, respectively. Arvinas released Phase 2 clinical trial results for ARV-471 in December, 2022 reporting a clinical benefit rate of 40% in CDK4/6 inhibitor-pretreated patients and an absence of dose-limiting toxicities.