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Development of RORalpha and RORgamma Ligands for Treatment of Behavioral Disorders

Award Number: R01MH092769
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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¿ DESCRIPTION (provided by applicant): The nuclear receptor superfamily (NR) and ligand regulated transcription factors that have proven to be a rich source of targets for development of drugs that target myriad human diseases. The retinoic acid receptor- related orphan receptors (RORs) are members of this superfamily and regulate several physiological processes including the circadian rhythm, neural development, metabolism and the immune response. Our data suggests that activation of RORa by synthetic ligands reduces autistic-behavior in mouse models while increasing the expression of key genes that are known to be downregulated in individuals with this disorder. ROR¿ inverse agonists that we discovered have been characterized for their ability to reduce proinflammatory TH17 cell differentiation, which has been shown to be associated with depression. In fact, treatment of mice with SR1001 (a ROR¿ inverse agonist) reduces depression-like behavior. We hypothesize that optimized RORa agonists may hold utility in treatment of autism and that optimized ROR¿ inverse agonists may hold utility in the treatment of depression. In order to address these hypotheses we propose the following 2 specific aims: Aim 1: Develop and optimize RORa agonists for treatment of autism and Aim 2: Develop and optimize ROR¿ inverse agonists for treatment of depression. The studies described in this application are highly innovative given that we have developed a range of novel, first-in-class ROR ligands and we have demonstrated that these compounds have efficacy in mouse models of autism as well as TH17 cell mediated diseases. If successful, this work would have significant impact given the potential translation of this work into drugs in the clinic.


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: 2022 ( Subtotal = $0 )
2022	2020	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	11	8/29/2022	NON-COMPETING CONTINUATION	$0


Issue Date FY: 2020 ( Subtotal = $502,895 )
2020	2020	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	11	1/24/2020	NON-COMPETING CONTINUATION	$502,895


Issue Date FY: 2019 ( Subtotal = $873,258 )
2019	2019	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	006	10	7/27/2019	SUPPLEMENT FOR EXPANSION	$402,527
2019	2019	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	005	10	2/5/2019	NON-COMPETING CONTINUATION	$470,731
2019	2018	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	004	9	2/4/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$127,383
2019	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	8	1/15/2019	NON-COMPETING CONTINUATION	-$536,393
2019	2018	ST. LOUIS COLLEGE OF PHARMACY	4588 PARKVIEW PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	9	1/16/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$536,393
2019	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	003	8	2/4/2019	NON-COMPETING CONTINUATION	-$59,600
2019	2017	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	002	7	2/4/2019	NON-COMPETING CONTINUATION	-$67,783


Issue Date FY: 2018 ( Subtotal = $595,993 )
2018	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	8	6/15/2018	NON-COMPETING CONTINUATION	$59,600
2018	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	8	1/31/2018	NON-COMPETING CONTINUATION	$536,393


Issue Date FY: 2017 ( Subtotal = $595,993 )
2017	2017	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	7	1/28/2017	NON-COMPETING CONTINUATION	$536,393
2017	2017	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	001	7	6/21/2017	NON-COMPETING CONTINUATION	$59,600


Issue Date FY: 2016 ( Subtotal = $662,214 )
2016	2016	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	000	6	2/15/2016	COMPETING CONTINUATION	$662,214


Issue Date FY: 2014 ( Subtotal = $603,988 )
2014	2014	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	002	4	8/21/2014	NON-COMPETING CONTINUATION	-$707,585
2014	2014	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Mental Health Research Grants	003	5	8/21/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$567,190
2014	2014	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	4	12/28/2013	NON-COMPETING CONTINUATION	$669,945
2014	2014	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	001	4	5/15/2014	NON-COMPETING CONTINUATION	$74,438


Issue Date FY: 2013 ( Subtotal = $714,610 )
2013	2013	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	001	3	6/10/2013	NON-COMPETING CONTINUATION	$44,663
2013	2013	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	3	11/23/2012	NON-COMPETING CONTINUATION	$669,947


Issue Date FY: 2012 ( Subtotal = $744,383 )
2012	2012	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	001	2	4/19/2012	NON-COMPETING CONTINUATION	$64,299
2012	2012	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	2	11/3/2011	NON-COMPETING CONTINUATION	$680,084


Issue Date FY: 2011 ( Subtotal = $814,847 )
2011	2011	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	12/24/2010	NEW	$814,847


Grand Total All Awards = $6,108,181

Sum of Action Amount is $6,108,181;

Grand Total = $6,108,181

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Development of RORalpha and RORgamma Ligands for Treatment of Behavioral Disorders

Award Number: R01MH092769

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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