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Development of a high-throughput screen to detect the effects of both pre- and post-biotransformed compounds for enhanced content drug discovery workflows

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44GM112241-02
Agency Tracking Number: R44GM112241
Amount: $996,512.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-30
Award End Date (Contract End Date): 2019-08-31
Small Business Information
2450 EJ CHAPMAN DR
Knoxville, TN 37996-0001
United States
DUNS: 968832498
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 GARY SAYLER
 (865) 974-8080
 sayler@utk.edu
Business Contact
 STEVEN RIPP
Phone: (865) 974-9605
Email: steven.ripp@490biotech.com
Research Institution
N/A
Abstract

Development of a high throughput screen to detect the effects of both preand postbiotransformed compounds for enhanced content drug discovery workflows
Project Summary
This Small Business Innovation Research Phase II project will build upon our successful Phase I demonstration
that substrate free autobioluminescent signal generation can detect both the preand post biotransformed
metabolic impacts of therapeutic compounds from a single plate based assayHerewe will leverage this
technology to develop a panel of industry relevant autobioluminescent cell lines optimized for the detection of
preand post biotransformed compound metabolic impacts and the identification of specific detoxification
pathway activation using modern three dimensionalDmicrophysiological culture systemsThese products
and their underlying technology will specifically address the National Institute of General Medical SciencesNIGMSrequest for novel in vivo and in vitro methods for predicting the safety and toxicities of pharmacologic
agentsBy optimizing this technology to function within the industry preferredD microphysiological formatwe will address the critical need for new methods that can both identify compound toxicity and elucidate the
mechanisms through which cells mitigate the compoundseffectsThe autonomous nature of this technology will
increase toxicological data acquisition while preserving the critical advantage of presenting physiologicallyrelevant dataand reducing the cost of performance by eliminating substratesreducing complexitylimiting
hands on operation timeobviating the need for sample destructionand reducing the potential for measurement
errorThrough the validation of this technology at a scale relevant to tierdrug discovery screening and its
comparative analysis against the existing gold standard ATP content assaythis revolutionary approach is poised
to have a significant and immediate impact towards reducing the estimated $ B year in unnecessary
expenditures made by pharmaceutical companies during their development of theof new compounds that
fail at the Phase I clinical trial stage due to misidentification of toxicological effects during tierscreeningThis
is possible becauseas demonstrated in our Phase I workthe use of our autobioluminescent technology
overcomes the high economic and logistical costs of existingtraditionally bioluminescent cell s requisite
chemical substrate additionwhich must co occur with each generation of signaland the intensive hands on
time necessitated to scale cultures due to their requisite sample destruction concurrent with imagingSimilarlyour autobioluminescent technology also obviates the hurdles presented by fluorescent cell s susceptibility to
autofluorescent signal inhibition and their tendency to remain active during downturns in cellular metabolism
or even after cell deathThe technology and products developed in this effort will therefore be capable of
significantly improving the throughput and effectiveness of microphysiological systems based tiercompound
screening to improve the efficiency and economics of new compound developmentand ultimatelyconsumer
safetyThis will allow them to thrive in a microphysiological system market that is predicted to maintain a
compound annual growth rate ofto exceed $B globally by

* Information listed above is at the time of submission. *

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