The pharmaceutical industry is under growing scrutiny due to the high failure rate in the clinic and the exorbitant cost of research resulting in expensive medications and growing healthcare expenditures. Increased research and development budgets have had little effect on drugs entering the market place, so clearly a new paradigm for drug discovery is needed to face the healthcare challenges of the 21st century. MEDROS has a long term goal of impacting the pharmaceutical industry by putting better drugs into the clinic through the development of a different approach to drug discovery. MEDROS was founded on a proprietary platform that uses fruit fly models of human diseases to search for novel medicines. An important proof-of-concept for our technology came from our academic collaborators who used this approach to demonstrate activity of a drug now in Phase III clinical trials for Medullary Thyroid Carcinoma. The technology uses high-throughput whole organism drug screening to quickly assess chemical compound efficacy, potency, compound stability, safety, and bioavailability all in one experiment. To further leverage the advantages of Drosophila drug discovery, the aims in this proposal are designed to develop Drosophila as a tool for molecular pathway mapping. This proposal is designed to address the one important liability common to all phenotypic screens, the fact that mechanism of action for hits emerging from the screen is typically not known. MEDROS is uniquely suited to tackle this problem by combining the power of Drosophila genetics with genomic and chemical biology tools. In this Proposal, two in situ mapping approaches will be developed as the starting point for this process. First, we will assess and validate the use of classical genetic modifier screening as a tool for identifying signalling pathways altered by individual chemical compounds. Second, we will use microarray analysis to generate 'fingerprint'expression patterns useful for determining pathways altered by compounds. Successful deployment of a process to easily and accurately define mechanism of action will provide an important extension to our approach, and provide avenues for potential strategic partnerships. , ,
Public Health Relevance: Drug discovery faces ever-increasing difficulties as the demand for sophisticated, effective therapeutics grows. MEDROS has developed a whole animal drug screening method to address this need by emphasizing whole animal compound screening. This proposal further uses the fruit fly D. melanogaster to identify the factors targeted by new generation candidate therapeutics.
Thesaurus Terms: Address;Animals;Assay;Bioassay;Bioavailability;Biochemical;Biologic Assays;Biologic Availability;Biological Assay;Biological Availability;Biology;Budgets;Businesses;C Cell Carcinoma;Cancer Genes;Cancer-Promoting Gene;Care, Health;Cell Communication And Signaling;Cell Signaling;Chemicals;Clinic;Clinical Trials;Clinical Trials, Phase Iii;Clinical Trials, Unspecified;Complex;Cost Of Illness;Development;Development And Research;Diabetes Mellitus;Disease;Disease Costs;Disease Model;Disorder;Drosophila;Drosophila Genus;Drug Delivery;Drug Delivery Systems;Drug Evaluation, Preclinical;Drug Industry;Drug Screening;Drug Targeting;Drug Targetings;Drugs;Epithelium;Evaluation Studies, Drug, Pre-Clinical;Evaluation Studies, Drug, Preclinical;Exhibits;Expenditure;Flr;Face;Failure (Biologic Function);Fingerprint;Flies;Fruit Fly, Drosophila;Generations;Genetic;Genetic Screening;Genomics;Goals;Healthcare;Heterogeneity;In Situ;In Vitro;Individual;Industry, Pharmaceutic;Intracellular Communication And Signaling;Lead;Libraries;Maps;Marketing;Medication;Medicine;Medullary Thyroid Cancer;Medullary Carcinoma Of Thyroid;Methods;Methods And Techniques;Methods, Other;Microarray Analysis;Microarray-Based Analysis;Modeling;Molecular;Oncogenes;Parafollicular Cell Carcinoma;Pathway Interactions;Pattern;Pb Element;Pharmaceutic Preparations;Pharmaceutical Industry;Pharmaceutical Preparations;Phase 3 Clinical Trials;Phase Iii Clinical Trials;Physiologic Availability;Position;Positioning Attribute;Preclinical Drug Evaluation;Process;R & D;R&D;Research;Safety;Science Of Medicine;Screening Procedure;Services;Sickness Cost;Signal Pathway;Signal Transduction;Signal Transduction Pathway;Signal Transduction Systems;Signaling;Solid Neoplasm;Solid Tumor;System;System, Loinc Axis 4;Techniques;Technology;Testing;Therapeutic;Thyroid Gland Medullary Carcinoma;Toxic Effect;Toxicities;Transforming Genes;Whole Organism;Animal Efficacy;Base;Bioavailability Of Drug;Biological Signal Transduction;Clinical Investigation;Cost;Design;Designing;Diabetes;Disease/Disorder;Disorder Model;Drug Discovery;Drug/Agent;Experiment;Experimental Research;Experimental Study;Facial;Failure;Fly;Fruit Fly;Heavy Metal Pb;Heavy Metal Lead;Human Disease;Improved;Medullary Thyroid Carcinoma;Microarray Technology;New Therapeutics;Next Generation Therapeutics;Novel;Novel Therapeutics;Pathway;Pathway Tools;Phase 3 Study;Phase 3 Trial;Phase Iii Trial;Protocol, Phase Iii;Public Health Relevance;Research And Development;Research Study;Screening;Screenings;Study, Phase Iii;Tissue Culture;Tool
