KPC34

KPC34 is a novel, orally bioavailable **phospholipid conjugate of gemcitabine**, developed to overcome several mechanisms of chemoresistance in hematologic malignancies[1][3][5][7]. Upon enzymatic activation by phospholipase C, KPC34 releases **gemcitabine monophosphate** and a **diacylglycerol mimetic**. Gemcitabine monophosphate bypasses the need for deoxycytidine kinase for activation, and the diacylglycerol mimetic acts as an inhibitor of conventional isoforms of **protein kinase C (PKC)**[1][3][5]. KPC34 uptake is independent of equilibrative nucleoside transporter 1 (ENT1) and is not a substrate for the multidrug resistance (MDR-1) efflux pump[1]. It has demonstrated high preclinical efficacy in models of **acute myeloid leukemia (AML)** and **acute lymphoblastic leukemia (ALL)**, particularly in models with activated PKC, and is able to cross the blood-brain barrier[1][3][5][7]. KPC34 is also being investigated for potential use in **pancreatic cancer**[2][6].