XMU-MP-8

XMU-MP-8 (SKPer1) is a potent molecular glue degrader that targets the oncogenic protein SKP2. It interacts with the F-box domain of SKP2 (Kd≈ 36 μM) and the N-terminal TPR domain of the E3 ligase STUB1 (Kd≈ 2.5 μM), leading to the formation of a stable SKP2-SKPer1-STUB1 ternary complex (Kd≈ 8.9 nM) . This interaction triggers the ubiquitination and proteasomal degradation of SKP2. XMU-MP-8 selectively eradicates cancer cells expressing SKP2 and exhibits notable tumor-suppressive effects in vivo along with a favorable safety profile. It is applicable in research on cancers such as non-small cell lung adenocarcinoma (NSCLC) and prostate adenocarcinoma.