Objective: Main goal is to extensive in-vivo efficacy validation alone and in combinations with current chemotherapeutics in xenograft mouse models of selected Smac mimetic along with detailed pharmacokinetic studies, initial toxicity studies. Under this focused objective, we will have following tasks:
1) Synthesis scale up and production of SMAC mimetic (S016-1348) at gram level
2) Detailed pharmacokinetic analysis of SMAC mimetic (S016-1348) via multiple routes
3) Multiple dose in-vitro and in-vivo efficacy determination of SMAC mimetic (S016-1348)
alone and in combinations with chemotherapeutics against therapy resistant colon cancer
4) Efficacy comparison with Phase-II Smac mimetic (LCL-161/Birinapant/AT406) molecules
and target validation studies of SMAC mimetic (S016-1348)
5) Evaluation of initial toxicity studies of SMAC mimetic (S016-1348) Summary: Hypertrilgyceridemia is characteristic feature of Indian dyslipidemic patients. Current therapies followed does not address this unmet need.This phytopharmaceutical is developed from leaves of Polyalthia longifolia, widely available pant in India. Bioactivity guided fractionation of alcoholic extract of the leaves lead to identification a novel class of anti-hyper triglyceridemic compounds with clerodane diterpene class. Anti-dyslipidemic activity has been profiled for the compounds/standardized extract. Bioactive four compounds are chosen as biomarker profiling. Standardized extract has exhibited comparable anti-hypertriglyceridemic activity to the clinically used standard anti-dyslipidemic compounds. | 
