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DISCOVERY OF INHIBITORS OF PTH-WNT SIGNALING SYNERGY IN BONE CELLS

Award Number: R43AR060111
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2010
PERIOD OF PERFORMANCE END DATE: 06/30/2011

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DISCOVERY OF INHIBITORS OF PTH-WNT SIGNALING SYNERGY IN BONE CELLS - DESCRIPTION (provided by applicant): Project Summary Description Title: Discovery of Inhibitors of PTH-Wnt Signaling Synergy in Bone Cells. Osteoporosis is a growing problem in the aged and an unfortunately large disease market and burden to the healthcare industry. This debilitating disease costs $18 billion in healthcare costs annually in the US and affects 10 million people in the US and an estimated 100 million worldwide. Brittle bone disease is expected to increase in incidence in the years to come due to an aging US and worldwide population. DiscoveryBioMed, Inc., the University of Alabama at Birmingham (UAB) Research Foundation, and Dr. Xu Cao (a world renowned bone cell signaling researcher previously with UAB and currently with Johns Hopkins) has forged a research collaboration to discover small molecule therapeutics that prevent osteoporosis. DBM has developed a light-based assay to find inhibitors of synergistic parathyroid hormone (PTH) and Wnt signaling pathways. DBM seeks to "multiplex" this high-throughput screening (HTS) friendly bioassay with additional light-based endpoints in cellular lysates and in the supernatant collected before cell lysis to monitor a series of endpoints relevant to osteoporosis drug discovery. Most importantly, this screening program utilizes a mammalian bone cell line as the biologically relevant cellular platform. Milestone 1 of this program seeks to fully design and optimize each individually light-based assay for each desired biological endpoint. Milestone 2 seeks to "multiplex" each individual assay into one powerful primary HTS bioassay. Milestone 3 seeks to screen the first 20,000 small molecules from a diverse set of synthetic organic compounds and natural product-derived phytochemicals. As a transition to planned Phase 2 research, DBM will assess hit-to-lead compounds early and often with cheminformatics tools to identify commonality in structure among the hit small molecules. This process allows parallel targeted work on lead compounds of interest already identified, while random screening proceeds. DBM will apply its core principles of drug discovery to this program that include: (a) screening on a biologically relevant cell platform (i.e., bone cells); (b) screening with both targeted and phenotypic intent and endpoints; (c) screening each test small molecule in triplicate to provide biostatistical power to the primary HTS experiment; and (d) assessing multiple high-content endpoints in primary HTS bioassay and in carefully scripted secondary validation experiments with Dr. Cao's research group. Based on the work accomplished thus far, DBM anticipates a strong outcome from this osteoporosis drug discovery program. PUBLIC HEALTH RELEVANCE: Public Health Relevance Statement Osteoporosis is a $ billion burden to the healthcare industry, with 10 million people affected in the US and an estimated 100 million affected worldwide. "Brittle bone disease" is expected to increase in incidence in the years to come due to an aging US and worldwide population. DiscoveryBioMed, Inc., the UAB Research Foundation, and Dr. Xu Cao and coworkers from Johns Hopkins have formed a triangular research collaboration to find new small molecule therapeutics to control and cure osteoporosis that work at the cellular and molecular level within bone tissue.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $234,330 )
2010	2010	DISCOVERY BIOMED LLC	1500 FIRST AVENUE NORTH	BIRMINGHAM	AL	35203	JEFFERSON	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/5/2010	NEW	$234,330
														Subtotal = $234,330

Grand Total All Awards = $234,330

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DISCOVERY OF INHIBITORS OF PTH-WNT SIGNALING SYNERGY IN BONE CELLS

Award Number: R43AR060111

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2010

PERIOD OF PERFORMANCE END DATE: 06/30/2011

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