Abstract
Abstract Jasco Pharmaceuticals has developed a novel and selective pan-PIM inhibitor (JP_11646) that has demonstrated biochemical IC50s of 24, 0.5 and 1 nM for PIM1, PIM2 and PIM3 respectively. Jasco also developed an engineered cell line to measure PIM2 transphosphorylation by over-expressing human PIM2 in human HEK293 cells together with human BAD as the substrate. The cell based assay measures the phosphorylation levels of BAD at Ser112 attributed solely to PIM2. JP_11646 exhibited a 590 nM IC50 in this cell based PIM2 assay confirming the MOA. JP_11646 increases apoptosis and decreases cell viability in multiple myeloma cell lines with the t(14;16) and t(4;14) translocations, which are known markers for poor prognosis. JP_11646 is orally bioavailable and has demonstrated in vivo efficacy, inhibiting tumor growth by >80% in a MM1.S tumor xenograft study. These data provide solid rationale for further development of JP_11646 as a targeted therapy for specific population of multiple myeloma patients that exhibit these genetic markers. Citation Format: Carmen M. Baldino, Justin Caserta, Stephane Dumas, Yvonne Flanders, Jayakumar Nair, Kelvin P. Lee. PIM2 inhibitor as a targeted therapy for the treatment of multiple myeloma patients with specific genetic signatures. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1049. doi:10.1158/1538-7445.AM2013-1049
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
