A novel treatment approach for low grade lymphoproliferative disorders using PKC412 (CGP41251), an inhibitor of protein kinase C.

Introduction: PKC412 (formally CGP41251) selectively inhibits protein kinase C (PKC) isoforms and has been shown to be cytotoxic to malignant cells in vitro. We have undertaken a single centre, open-label, multi-dose, exploratory Phase II clinical trial of PKC412 in patients with CLL and low grade NHL.

Methods: Thirteen CLL patients and eight stage IV NHL patients were treated at three oral dose levels of 25, 150 and 225 mg/day for 14 days.

Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro.

Background And Objectives: The staurosporine derivative PKC412 (CGP41251) is a more selective inhibitor of the conventional isoforms of protein kinase C (PKC) than is the parent compound. In addition to its growth inhibitory properties, PKC412 reverses the efflux function of the multidrug resistance (MDR)-1 gene product, P-glycoprotein (P-gp).

Design And Methods: The in vitro actions of PKC412 were investigated in peripheral blood lymphocytes (PBL) from 4 normal volunteers, B-cell isolates from 3 normal tonsils and 31 patients with B-cell chronic lymphocytic leukemia (B-CLL).