Epistimi Inc

OXIDIZED-PROTEIN TARGETED DEGRADATION: A FIRST-IN-CLASS THERAPEUTIC STRATEGY TO COMBAT OXIDATIVE DAMAGE IN ALS

DEMOCRATIZING CHEMICAL PROTEOMICS: A PLATFORM FOR SAME-DAY PHOTOAFFINITY PROBES TO DRIVE WHOLE-PROTEOME SELECTIVITY IN CANCER DRUG DISCOVERY - PROJECT SUMMARY/ABSTRACT CANCER DRUG DISCOVERY CONTINUES TO FACE EXCEPTIONALLY HIGH ATTRITION RATES, WITH NEARLY 90% OF CLINICAL CANDIDATES FAILING DUE TO INSUFFICIENT EFFICACY OR UNACCEPTABLE TOXICITY. A KEY DRIVER OF THIS ATTRITION IS THE LACK OF SYSTEMATIC TOOLS TO ASSESS DRUG SELECTIVITY EARLY IN DEVELOPMENT. CURRENT CHEMOPROTEOMIC METHODS ENABLE PROTEOME-WIDE MAPPING ONLY FOR A LIMITED FRACTION OF DRUGS: COVALENT CYSTEINE-REACTIVE PROBES (~10% OF FDA-APPROVED CANCER DRUGS) AND AMINE-BASED PHOTOAFFINITY PROBES (~20%). AS A RESULT, THE VAST MAJORITY OF DRUG CHEMICAL SPACE AND HUMAN PROTEINS REMAIN INACCESSIBLE TO UNBIASED PROFILING, LEAVING OFF-TARGET TOXICITIES AND EFFICACY BOUNDARIES UNDEFINED UNTIL LATE CLINICAL STAGES. THIS PROJECT WILL DEVELOP AND VALIDATE A FIRST-IN-CLASS, SYNTHESIS-FREE, SCAFFOLD-AGNOSTIC PLATFORM FOR THE RAPID GENERATION OF STOCHASTIC PHOTOAFFINITY PROBES (ST-AFBPS). THE CORE INNOVATION LIES IN TRIFUNCTIONAL DIAZIRINE/DIAZIRIDINE BUILDING BLOCKS THAT ALLOW THE SAME-DAY CONVERSION OF VIRTUALLY ANY SMALL MOLECULE INTO A PROTEOMIC PROBE, ELIMINATING THE NEED FOR RATIONAL PROBE DESIGN AND BESPOKE SYNTHESIS. THESE PROBES ARE CELL-PERMEABLE AND CAPTURE PROTEIN INTERACTIONS DIRECTLY IN LIVE CELLS, ENABLING THE CONSTRUCTION OF STRUCTURE–PROTEOME SELECTIVITY RELATIONSHIPS (SPSRS). THE RESEARCH WILL PROCEED THROUGH THREE AIMS: (1) SYNTHESIS OF FIVE DISTINCT ST-AFBP BUILDING BLOCKS WITH VARIED PHOTOCHEMICAL PROPERTIES; (2) ESTABLISHMENT OF THE STOCHASTIC PHOTOMODIFICATION PROTOCOL AND BENCHMARKING OF ST-AFBPS AGAINST RATIONALLY DESIGNED PROBES USING DIVERSE FDA-APPROVED CANCER DRUGS; AND (3) APPLICATION OF THE PLATFORM TO PROFILE PROTEOME-WIDE SELECTIVITY LANDSCAPES ACROSS MULTIPLE CANCER MODELS, INCLUDING RESISTANT VARIANTS, WITH BIOINFORMATIC CORRELATION TO KNOWN TOXICITY AND EFFICACY PATHWAYS. COMPLETION OF THESE AIMS WILL DELIVER A BROADLY APPLICABLE CHEMICAL PROTEOMICS TECHNOLOGY THAT DEMOCRATIZES PROBE GENERATION, EXPANDS PROTEOME COVERAGE WELL BEYOND CURRENT METHODS, AND ENABLES THE EARLY IDENTIFICATION OF DRUG SELECTIVITY LIABILITIES. THE LONG-TERM IMPACT IS TO REDUCE CLINICAL ATTRITION IN ONCOLOGY AND ACCELERATE THE DEVELOPMENT OF SAFER, MORE EFFECTIVE CANCER THERAPEUTICS.

TAS::57 3600::TAS "CORROSION RESISTANCE OF HIGH-TEMPERATURE SMAS UNDER EXTREME ENVIRONMENTS" (THE GRANTEE'S TECHNICAL PROPOSAL DATE APR 11, 2016)

WIRELESS ACCESS INFRASTRUCTURES EXPANSIONS THROUGH OPPORTUNISTIC NETWORKS

HEAT TREATMENTS FOR IMPROVED ORGANIC-COMPATIBLE DISINFESTATION OF KHAPRA BEETLE IN STORED PRODUCTS

CSP - THE TWENTY-SIXTH (2016) INTERNATIONAL OCEAN AND POLAR ENGINEERING CONFERENCE