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Publications

#OverPowerRett

Allosteric Modulation of Metabotropic Glutamate Receptors for the Treatment of Neurodevelopmental Disorders

Video

2023

Differential Activity of Orthosteric Agonists and Allosteric Modulators at Metabotropic Glutamate Receptor 7Molecular Pharmacology. 2023 Jul (104(1)). 17-27

There is no publication with 2022 tag

2021

HofmannCS, CarringtonSJ, KellerAN, GregoryKJ, NiswenderCM, Regulation and Functional Consequences of mGlu RNA EditingRNA (New York, N.Y.). 2021 Jul 8

JoffeME, SantiagoCI, VermudezSAD, FisherNM, DograS, NiswenderCM, Jeffrey ConnP, Frontal cortex genetic ablation of metabotropic glutamate receptor subtype 3 (mGlu) impairs postsynaptic plasticity and modulates affective behaviorsNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2021 May 25

VermudezSAD, GogliottiRG, ArthurB, BuchA, MoralesC, MoxleyY, RajpalH, ConnPJ, NiswenderCM, Profiling beneficial and potential adverse effects of MeCP2 overexpression in a hypomorphic Rett syndrome mouse modelGenes, brain, and behavior. 2021 May 18 e12752

XiangZ, LvX, LinX, O'BrienDE, AltmanMK, LindsleyCW, JavitchJA, NiswenderCM, ConnPJ, Input-specific regulation of glutamatergic synaptic transmission in the medial prefrontal cortex by mGlu/mGlu receptor heterodimersScience signaling. 2021 Apr 6 14 (677).

DograS, StansleyBJ, XiangZ, QianW, GogliottiRG, NicolettiF, LindsleyCW, NiswenderCM, JoffeME, ConnPJ, Activating mGlu Metabotropic Glutamate Receptors Rescues Schizophrenia-like Cognitive Deficits Through Metaplastic Adaptations Within the HippocampusBiological psychiatry. 2021 Mar 6

KentCN, FultonMG, StillwellKJ, DickersonJW, LochMT, RodriguezAL, BlobaumAL, BoutaudO, RookJL, NiswenderCM, Jeffrey ConnP, LindsleyCW, Discovery and optimization of a novel CNS penetrant series of mGlu PAMs based on a 1,4-thiazepane core with in vivo efficacy in a preclinical Parkinsonian modelBioorganic & medicinal chemistry letters. 2021 Feb 5 127838

FisherNM, AlHashimA, BuchAB, BadivukuH, SammanMM, WeissKM, CesteroGI, DoesMD, RookJM, LindsleyCW, ConnPJ, GogliottiRG, NiswenderCM, A GRM7 mutation associated with developmental delay reduces mGlu7 expression and produces neurological phenotypesJCI insight. 2021 Jan 21

2020

DavisDC, BungardJD, ChangS, RodriguezAL, BlobaumAL, BoutaudO, MelanconBJ, NiswenderCM, Jeffrey ConnP, LindsleyCW, Lead optimization of the VU0486321 series of mGlu PAMs. Part 4: SAR reveals positive cooperativity across multiple mGlu receptor subtypes leading to subtype unselective PAMsBioorganic & medicinal chemistry letters. 2020 Nov 27 32 127724

KalbfleischJJ, ReedCW, ParkC, SpearingPK, QuitaligMC, JenkinsMT, RodriguezAL, BlobaumAL, ConnPJ, NiswenderCM, LindsleyCW, Synthesis and SAR of a series of mGlu NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate coreBioorganic & medicinal chemistry letters. 2020 Sep 2 30 (22). 127529

ReedCW, KalbfleischJJ, WongMJ, WashecheckJP, HunterA, RodriguezAL, BlobaumAL, ConnPJ, NiswenderCM, LindsleyCW, Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu Positive Allosteric Modulator Tool Compound ACS medicinal chemistry letters. 2020 Aug 20 11 (9). 1773-1779

FultonMG, LochMT, RodriguezAL, LinX, JavitchJA, ConnPJ, NiswenderCM, LindsleyCW, Synthesis and pharmacological evaluation of bivalent tethered ligands to target the mGlu heterodimeric receptor results in a compound with mGlu homodimer selectivityBioorganic & medicinal chemistry letters. 2020 Apr 25 30 (13). 127212

FisherNM, GouldRW, GogliottiRG, McDonaldAJ, BadivukuH, ChennareddyS, BuchAB, MooreAM, JenkinsMT, RobbWH, LindsleyCW, JonesCK, ConnPJ, NiswenderCM, Phenotypic profiling of mGlu knockout mice reveals new implications for neurodevelopmental disordersGenes, brain, and behavior. 2020 Apr 14 19 (7). e12654

2019

FultonMG, LochMT, CuocoCA, RodriguezAL, DaysE, VinsonPN, KozekKA, WeaverCD, BlobaumAL, ConnPJ, NiswenderCM, LindsleyCW, Challenges in the Discovery and Optimization of mGlu Heterodimer Positive Allosteric ModulatorsLetters in drug design & discovery. 2019 Dec 16 16 (12). 1387-1394

MoranSP, XiangZ, DoyleCA, MaksymetzJ, LvX, FaltinS, FisherNM, NiswenderCM, RookJM, LindsleyCW, ConnPJ, Biased M receptor-positive allosteric modulators reveal role of phospholipase D in M-dependent rodent cortical plasticityScience signaling. 2019 Dec 3 12 (610).

GregoryKJ, BridgesTM, GogliottiRG, StaufferSR, NoetzelMJ, JonesCK, LindsleyCW, ConnPJ, NiswenderCM, In Vitro to in Vivo Translation of Allosteric Modulator Concentration-Effect Relationships: Implications for Drug DiscoveryACS pharmacology & translational science. 2019 Nov 15 2 (6). 442-452

TempleKJ, EngersJL, LongMF, WatsonKJ, ChangS, LuscombeVB, JenkinsMT, RodriguezAL, NiswenderCM, BridgesTM, ConnPJ, EngersDW, LindsleyCW, Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M positive allosteric modulator (PAM) chemotypeBioorganic & medicinal chemistry letters. 2019 Nov 13 30 (3). 126812

TempleKJ, LongMF, EngersJL, WatsonKJ, ChangS, LuscombeVB, RodriguezAL, NiswenderCM, BridgesTM, ConnPJ, EngersDW, LindsleyCW, Discovery of structurally distinct tricyclic M positive allosteric modulator (PAM) chemotypesBioorganic & medicinal chemistry letters. 2019 Nov 11 30 (4). 126811

PresleyCC, PerryCK, ChildressES, MulderMJ, LuscombeVB, RodriguezAL, NiswenderCM, ConnPJ, LindsleyCW, Evaluation of Synthetic Cytochrome P-Mimetic Metalloporphyrins To Facilitate “Biomimetic” Biotransformation of a Series of mGlu Allosteric LigandsACS omega. 2019 Jul 26 4 (7). 12782-12789

ChopkoTC, HanC, GregroAR, EngersDW, FeltsAS, PoslusneyMS, BollingerKA, MorrisonRD, BubserM, LamsalA, LuscombeVB, ChoHP, Schnetz-BoutaudNC, RodriguezAL, ChangS, DanielsJS, StecDF, NiswenderCM, JonesCK, WoodMR, WoodMW, DugganME, BrandonNJ, ConnPJ, BridgesTM, LindsleyCW, MelanconBJ, SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel, CNS penetrant tricyclic M PAMsBioorganic & medicinal chemistry letters. 2019 Jun 20 29 (16). 2224-2228

XiangZ, LvX, MaksymetzJ, StansleyBJ, GhoshalA, GogliottiRG, NiswenderCM, LindsleyCW, ConnPJ, mGlu Positive Allosteric Modulators Facilitate Long-Term Potentiation via Disinhibition Mediated by mGlu-Endocannabinoid SignalingACS pharmacology & translational science. 2019 May 15 2 (3). 198-209

GogliottiRG, NiswenderCM, A Coordinated Attack: Rett Syndrome Therapeutic DevelopmentTrends in pharmacological sciences. 2019 Apr 1 40 (4). 233-236

ReedCW, YohnSE, WashecheckJP, RoenfanzHF, QuitaligMC, LuscombeVB, JenkinsMT, RodriguezAL, EngersDW, BlobaumAL, ConnPJ, iswenderCM, LindsleyCW, Discovery of an Orally Bioavailable and CNS-Penetrant mGlu NAM (VU6012962) Journal of Medicinal Chemistry. 2019 Jan 17. 62 (3). 1690-1695

2018

PoslusneyMS, SalovichJM, WoodMR, MelanconBJ, BollingerKA, LuscombeVB, RodriguezAL, EngersDW, BridgesTM, NiswenderCM, ConnPJ, LindsleyCW, Novel M positive allosteric modulators derived from questioning the role and impact of a presumed intramolecular hydrogen-bonding motif in β-amino carboxamide-harboring ligandsBioorganic & medicinal chemistry letters. 2018 Dec 18 29 (3). 362-366

FisherNM, SetoM, LindsleyCW, NiswenderCM, Corrigendum: Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental DisordersFrontiers in molecular neuroscience. 2018 Dec 14 11 444

FeltsAS, BollingerKA, BrassardCJ, RodriguezAL, MorrisonRD, Scott DanielsJ, BlobaumAL, NiswenderCM, JonesCK, ConnPJ, EmmitteKA, LindsleyCW, Discovery of 4-alkoxy-6-methylpicolinamide negative allosteric modulators of metabotropic glutamate receptor subtype 5Bioorganic & medicinal chemistry letters. 2018 Nov 10 29 (1). 47-50

FisherNM, SetoM, LindsleyCW, NiswenderCM, Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental DisordersFrontiers in molecular neuroscience. 2018 Oct 23 11 387

MarksCR, ShonesyBC, WangX, StephensonJR, NiswenderCM, ColbranRJ, Activated CaMKII Binds to the mGlu Metabotropic Glutamate Receptor and Modulates Calcium MobilizationMolecular pharmacology. 2018 Oct 3 94 (6). 1352-1362

EngersJL, ChildressES, LongMF, CapstickRA, LuscombeVB, ChoHP, DickersonJW, RookJM, BlobaumAL, NiswenderCM, EngersDW, ConnPJ, LindsleyCW, VU6007477, a Novel M PAM Based on a Pyrrolo[2,3-]pyridine Carboxamide Core Devoid of Cholinergic Adverse EventsACS medicinal chemistry letters. 2018 Sep 4 9 (9). 917-922

EngersJL, BenderAM, KalbfleischJJ, ChoHP, LingenfelterKS, LuscombeVB, HanC, MelanconBJ, BlobaumAL, DickersonJW, RookJM, NiswenderCM, EmmitteKA, ConnPJ, LindsleyCW, Discovery of Tricyclic Triazolo- and Imidazopyridine Lactams as M Positive Allosteric ModulatorsACS chemical neuroscience. 2018 Aug 9 10 (3). 1035-1042

BertronJL, ChoHP, Garcia-BarrantesPM, PanareseJD, SalovichJM, NanceKD, EngersDW, RookJM, BlobaumAL, NiswenderCM, StaufferSR, ConnPJ, LindsleyCW, The discovery of VU0486846: steep SAR from a series of M PAMs based on a novel benzomorpholine coreBioorganic & medicinal chemistry letters. 2018 May 5 28 (12). 2175-2179

MoranSP, ChoHP, MaksymetzJ, RemkeDH, HansonRM, NiswenderCM, LindsleyCW, RookJM, ConnPJ, PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native SystemsACS chemical neuroscience. 2018 Apr 25 9 (9). 2218-2224

FeltsAS, RodriguezAL, MorrisonRD, BlobaumAL, ByersFW, DanielsJS, NiswenderCM, ConnPJ, LindsleyCW, EmmitteKA, Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5Bioorganic & medicinal chemistry letters. 2018 Apr 22 28 (10). 1679-1685

FeltsAS, RodriguezAL, MorrisonRD, BlobaumAL, ByersFW, DanielsJS, NiswenderCM, ConnPJ, LindsleyCW, EmmitteKA, Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5Bioorganic & medicinal chemistry letters. 2018 Apr 22 28 (10). 1679-1685

O'BrienDE, ShawDM, ChoHP, CrossAJ, WesolowskiSS, FeltsAS, BergareJ, ElmoreCS, LindsleyCW, NiswenderCM, ConnPJ, Differential Pharmacology and Binding of mGlu Receptor Allosteric ModulatorsMolecular pharmacology. 2018 Mar 15 93 (5). 526-540

MoranSP, DickersonJW, ChoHP, XiangZ, MaksymetzJ, RemkeDH, LvX, DoyleCA, RajanDH, NiswenderCM, EngersDW, LindsleyCW, RookJM, ConnPJ, M-positive allosteric modulators lacking agonist activity provide the optimal profile for enhancing cognitionNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2018 Mar 14 43 (8). 1763-1771

2017

StansleyBJ, FisherNM, GogliottiRG, LindsleyCW, ConnPJ, NiswenderCM, Contextual Fear Extinction Induces Hippocampal Metaplasticity Mediated by Metabotropic Glutamate Receptor 5Cerebral cortex (New York, N.Y. : 1991). 2017 Nov 9 28 (12). 4291-4304

StansleyBJ, FisherNM, GogliottiRG, LindsleyCW, ConnPJ, NiswenderCM, Contextual Fear Extinction Induces Hippocampal Metaplasticity Mediated by Metabotropic Glutamate Receptor 5Cerebral cortex (New York, N.Y. : 1991). 2017 Nov 9 28 (12). 4291-4304

ReedCW, McGowanKM, SpearingPK, StansleyBJ, RoenfanzHF, EngersDW, RodriguezAL, EngelbergEM, LuscombeVB, LochMT, RemkeDH, RookJM, BlobaumAL, ConnPJ, NiswenderCM, LindsleyCW, VU6010608, a Novel mGlu NAM from a Series of -(2-(1-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamidesACS medicinal chemistry letters. 2017 Nov 8 8 (12). 1326-1330

2016

SenterRK, GhoshalA, WalkerAG, XiangZ, NiswenderCM, ConnPJ, The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic StrategiesCurrent neuropharmacology. 2016 Jul 2 14 (5). 455-73

LindsleyCW, EmmitteKA, HopkinsCR, BridgesTM, GregoryKJ, NiswenderCM, ConnPJ, Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate ReceptorsChemical reviews. 2016 Feb 16 116 (11). 6707-41

2014

HanC, ChatterjeeA, NoetzelMJ, PanareseJD, SmithE, ChaseP, HodderP, NiswenderC, ConnPJ, LindsleyCW, StaufferSR, Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulatorsBioorganic & medicinal chemistry letters. 2014 Nov 18 25 (2). 384-8

ConnPJ, LindsleyCW, MeilerJ, NiswenderCM, Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disordersNature reviews. Drug discovery. 2014 Sep 3 13 (9). 692-708

YinS, NiswenderCM, Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indicationsCellular signalling. 2014 May 2 26 (10). 2284-97

WuH, WangC, GregoryKJ, HanGW, ChoHP, XiaY, NiswenderCM, KatritchV, MeilerJ, CherezovV, ConnPJ, StevensRC, Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulatorScience (New York, N.Y.). 2014 Mar 6 344 (6179). 58-64

2013

MankaJT, RodriguezAL, MorrisonRD, VenableDF, ChoHP, BlobaumAL, DanielsJS, NiswenderCM, ConnPJ, LindsleyCW, EmmitteKA, Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1Bioorganic & medicinal chemistry letters. 2013 Jul 23 23 (18). 5091-6

KleinMT, VinsonPN, NiswenderCM, Approaches for probing allosteric interactions at 7 transmembrane spanning receptorsProgress in molecular biology and translational science. 2013 Jun 15 115 1-59