KPG-121

KPG-121 is an orally administered, novel small molecule and lenalidomide analogue developed as a modulator of the Cereblon (CRBN) E3 ubiquitin ligase complex CRL4CRBN. It binds to CRL4-Cereblon with higher affinity than lenalidomide, resulting in enhanced immunomodulatory, anti-proliferative, and anti-angiogenic activities. Mechanistically, KPG-121 promotes rapid ubiquitination and degradation of casein kinase 1α (CK1α), Aiolos (IKZF3), and Ikaros (IKZF1) transcription factors. Preclinical studies have shown that KPG-121 demonstrates synergy with androgen receptor antagonists such as abiraterone, enzalutamide, apalutamide, and darolutamide in both in vitro and in vivo models. The drug is being developed primarily for metastatic castration-resistant prostate cancer (mCRPC), where it has advanced to phase II/III clinical trials in combination with abiraterone as first-line therapy[1][2][5][7][8]. Early-phase studies have also explored its use for other solid tumors and hematologic malignancies[4].

Other names

lenalidomide analog kpg-121