BKI-1553

BKI-1553 (also known as BKIDC-1553) is a small molecule bumped kinase inhibitor (BKI) developed by the University of Washington. Originally designed to target **calcium-dependent protein kinase 1 (CDPK1)** in apicomplexan parasites such as *Toxoplasma gondii*, *Neospora caninum*, and *Sarcocystis neurona*, it was subsequently investigated for the treatment of castration-resistant prostate cancer (CRPC). In prostate cancer models, BKI-1553 acts as a potent inhibitor of **hexokinase 2 (HK2)**, a key enzyme in the glycolytic pathway that is often overexpressed in high-grade tumors. By inhibiting HK2, BKI-1553 disrupts glycolysis, leading to rapid metabolic exhaustion and growth suppression in both androgen receptor (AR)-positive and AR-negative prostate cancer cells. Additionally, the compound has been shown to reduce AR expression and phosphorylation at Ser81, further contributing to its efficacy in AR-driven models. BKI-1553 is orally bioavailable and has demonstrated significant efficacy in various patient-derived xenograft (PDX) models.

Other names

Bumped kinase inhibitor 1553