Over 400,000 new cases of renal cell carcinoma (RCC) are detected annually worldwide. One-fourth of these patients are already in advanced stages when diagnosed; with current therapies, their predicted 5-year survivalrate is only 12%. To help curtail this loss of life, Bacchus Therapeutics has created a family of novel molecules that cause regression of tumors in preclinical animal models of RCC. These potential therapeutics provided long-term survival, rather than merely delaying tumor growth. These compounds also showed potency against othercancers driven by the MYC oncogene, including hepatocellular carcinoma and B-cell lymphoma.The goal of the proposed Phase I SBIR project is to characterize the biochemical traits and cytotoxicity of 7candidate molecules, which will determine a lead candidate for development into an effective drug against RCC.Initial studies will define the solubility of the molecules, as well as specificity for their target enzyme. Additionalwork will evaluate their relative toxicity to RCC versus normal cell lines. Based on these results, the candidatewith the highest specific potency will be tested in mouse models of RCC, using patient-derived xenografts thatexpress either high or low levels of MYC.Following the successful completion of these Aims, we will seek Phase II SBIR funding to undertake studies thatwill enable Investigational New Drug development. Through partnering or licensing, we plan to commercializethe lead compounds as a completely new therapeutic agent against advanced RCC. Future work will evaluatethis molecule or related analogs for treatment of other MYC-driven cancers. NARRATIVE Each year, over 100,000 people worldwide die from advanced renal cell carcinoma. Bacchus Therapeutics has created novel molecules that show potential to cause tumor regression and allow subsequent survival. In this SBIR proposal, we plan to characterize these compounds to determine the most potent one for drug development. Acyltransferase ; EC 2.3 ; Animals ; inhibitor/antagonist ; inhibitor ; Autopsy ; necropsy ; postmortem ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Renal Cell Carcinoma ; Grawitz Tumor ; Hypernephroid Carcinoma ; Hypernephroma ; Nephroid Carcinoma ; Renal Adenocarcinoma ; Renal Cell Adenocarcinoma ; Renal Cell Cancer ; kidney adenocarcinoma ; Cell Line ; CellLine ; Strains Cell Lines ; cultured cell line ; Clinical Trials ; Cessation of life ; Death ; Diagnosis ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Investigational Drugs ; Investigational New Drugs ; Enzymes ; Enzyme Gene ; Epithelial Cells ; Ethylmaleimide ; 1-ethyl-1H-pyrrole-2,5-dione ; N ethylmaleimide ; N-Ethylmaleimide ; Family ; Future ; Glucose ; D-Glucose ; Dextrose ; Glutamine ; Gln ; L-Glutamine ; Q Levoglutamide ; Q. Levoglutamide ; Goals ; Primary carcinoma of the liver cells ; Hepatocarcinoma ; Hepatocellular Carcinoma ; Hepatocellular cancer ; Hepatoma ; Liver Cells Carcinoma ; liver carcinoma ; Human ; Modern Man ; In Vitro ; Intraperitoneal Injections ; IP injection ; Kidney ; Kidney Urinary System ; renal ; Proximal Kidney Tubules ; renal proximal tubule ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Mus ; Mice ; Mice Mammals ; Murine ; Patients ; Phospholipids ; Phosphatides ; Phosphotransferases ; Kinases ; Phosphotransferase Gene ; Transphosphorylases ; Research ; Solubility ; Specificity ; Stress ; Survival Rate ; Testing ; Time ; cell transformation ; transformed cells ; Weight ; Work ; alpha-glycerophosphoric acid ; 1-phosphoglycerol ; alpha-glycerophosphate ; glycerol 1-phosphate ; glycerol 3-phosphate ; B-Cell Lymphomas ; B lymphoma ; Measures ; MYC gene ; Avian Myelocytomatosis Viral Oncogene Homolog ; myc Oncogenes ; Apoptosis ; Apoptosis Pathway ; Programmed Cell Death ; base ; Benign ; Clinical ; Phase ; Biochemical ; Hepatocyte ; Hepatic Cells ; Hepatic Parenchymal Cell ; Liver Cells ; Licensing ; analog ; Funding ; Therapeutic ; Therapeutic Agents ; Malignant Cell ; cancer cell ; Life ; Investigation ; Tumor Volume ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; Renal Cell ; kidney cell ; Lytotoxicity ; cytotoxicity ; adipogenesis ; lipogenesis ; lipid biosynthesis ; lipogenesis inhibitor ; membrane structure ; Membrane ; pleiotropic effect ; pleiotropy ; pleiotropism ; Receptor Protein ; receptor ; fat metabolism ; lipid metabolism ; tumor growth ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; trait ; aqueous ; Toxicities ; Toxic effect ; novel ; Pathogenesis ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Maximal Tolerated Dose ; Maximally Tolerated Dose ; Maximum Tolerated Dose ; Modeling ; drug development ; MYC Protein ; MYC Family Protein ; VEGF ; VEGFs ; Vascular Endothelial Growth Factors ; Normal Cell ; Induction of Apoptosis ; Apopain ; Apoptosis-Related Cysteine Protease Caspase 3 ; CASP-3 ; CASP3 ; CPP-32 ; CPP32 ; CPP32 protein ; CPP32B ; CPP32beta ; Cysteine Protease CPP32 ; Cysteine Protease CPP32 Gene ; PARP Cleavage Protease ; PARP Cleavage Protease Gene ; SCA-1 ; SCA-1 Gene ; SREBP Cleavage Activity 1 ; SREBP Cleavage Activity 1 Gene ; Yama ; Yama protein ; caspase-3 ; cysteine protease P32 ; CASP3 gene ; PD 1 ; PD-1 ; PD1 ; programmed cell death 1 ; programmed death 1 ; sle2 ; systemic lupus erythematosus susceptibility 2 ; programmed cell death protein 1 ; Dose ; Economic Burden ; in vivo ; in vivo Model ; BAY 54-9085 ; Sorafenib ; Malignant Epithelial Cell ; Carcinoma Cell ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Monitor ; Development ; developmental ; Pathway interactions ; pathway ; pre-clinical ; preclinical ; cost ; Outcome ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; mouse model ; murine model ; tumor ; screening ; small molecule inhibitor ; lead candidate ; in vivo evaluation ; in vivo testing ; Nivolumab ; Opdivo ; Lymphoma cell ; pembrolizumab ; Keytruda ; patient derived xenograft model ; PDX model ; Patient derived xenograft ; Prognosis ;
