Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65
Open accessAbstract
At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs.
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GPCRs are important off-targets for kinase inhibitors, ion channel modulators, anti-infectives and other drug-like molecules.
“GPCRs also represent important off-targets for kinase inhibitors62,63, ion channel modulators64, anti-infectives65 and other classes of drug-like molecules53,54.”
From Unexplored therapeutic opportunities in the human genome (2018) · cites this paper as [64]
52 non-olfactory GPCRs are categorized as Tdark, and new screening platforms have begun the process of illuminating them.
“Although 52 non-olfactory GPCRs are categorized as Tdark, the availability of new screening platforms to discover chemical matter for these GPCRs has begun the process of illumination64,67,68.”
From Unexplored therapeutic opportunities in the human genome (2018) · cites this paper as [64]
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Cites
Comparative Protein Structure Modeling Using Modeller
Eswar, N., Webb, B., Martı́-Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M., Pieper, U., & Šali, A. (2006) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi0506s15 · Cited by 4,564 · see citing works
ChEMBL: a large-scale bioactivity database for drug discovery
Gaulton, A., Bellis, L. J., Bento, A. P., Chambers, J., Davies, M., Hersey, A., Light, Y., McGlinchey, S., Michalovich, D., Al-Lazikani, B., et al. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr777 · Cited by 4,382 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Comparative Protein Structure Modeling Using MODELLER
Eswar, N., Webb, B., Martı́-Renom, M. A., Madhusudhan, M. S., Eramian, D., Shen, M., Pieper, U., & Šali, A. (2007) · Current Protocols in Protein Science · doi:10.1002/0471140864.ps0209s50 · Cited by 2,862 · see citing works
Relating protein pharmacology by ligand chemistry
Keiser, M. J., Roth, B. L., Armbruster, B. N., Ernsberger, P., Irwin, J. J., & Shoichet, B. K. (2007) · Nature Biotechnology · doi:10.1038/nbt1284 · Cited by 2,402 · see citing works
Self-citationArmbruster, B. N., Li, X., Pausch, M. H., Herlitze, S., & Roth, B. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700293104 · Cited by 2,046 · see citing works
Self-citationMumberg, D., Müller, R., & Funk, M. (1995) · Gene · doi:10.1016/0378-1119(95)00037-7 · Cited by 1,972 · see citing works
Borst, O., Walker, B., Münzer, P., Russo, A., Schmid, E., Faggio, C., Bigalke, B., Laufer, S., Gawaz, M., & Lang, F. J. W. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350110 · Cited by 1,867 · see citing works
Predicting new molecular targets for known drugs
Keiser, M. J., Setola, V., Irwin, J. J., Laggner, C., Abbas, A. I., Hufeisen, S. J., Jensen, N. H., Kuijer, M. B., Matos, R. C., Tran, T. B., et al. (2009) · Nature · doi:10.1038/nature08506 · Cited by 1,667 · see citing works
Self-citationOn the Role of the Crystal Environment in Determining Protein Side-chain Conformations
Jacobson, M. P., Friesner, R. A., Xiang, Z., & Honig, B. H. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00470-9 · Cited by 1,289 · see citing works
G Protein-Coupled Receptor Allosterism and Complexing
Christopoulos, A., & Kenakin, T. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.323 · Cited by 934 · see citing works
Self-citationAutomated design of ligands to polypharmacological profiles
Besnard, J., Ruda, G. F., Setola, V., Abecassis, K., Rodriguiz, R. M., Huang, X.-P., Norval, S., Sassano, M. F., Shin, A. I., Webster, L. A., et al. (2012) · Nature · doi:10.1038/nature11691 · Cited by 832 · see citing works
Self-citationProton-sensing G-protein-coupled receptors
Ludwig, M., Vanek, M., Guerini, D., Gasser, J. A., Jones, C. E., JUNKER, U., Hofstetter, H., Wolf, R. M., & Seuwen, K. (2003) · Nature · doi:10.1038/nature01905 · Cited by 746 · see citing works
Anatomical Profiling of G Protein-Coupled Receptor Expression
Regard, J. B., Sato, I. T., & Coughlin, S. R. (2008) · Cell · doi:10.1016/j.cell.2008.08.040 · Cited by 696 · see citing works
Grozinger, C. M., & Schreiber, S. L. (2002) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00092-3 · Cited by 537 · see citing works
Discovering potent and selective reversible inhibitors of enzymes in complex proteomes
Leung, D., Hardouin, C., Boger, D. L., & Cravatt, B. F. (2003) · Nature Biotechnology · doi:10.1038/nbt826 · Cited by 387 · see citing works
Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology
Leach, K., Sexton, P. M., & Christopoulos, A. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.06.004 · Cited by 362 · see citing works
Model for Aqueous Solvation Based on Class IV Atomic Charges and First Solvation Shell Effects
Chambers, C. C., Hawkins, G. D., Cramer, C. J., & Truhlar, D. G. (1996) · The Journal of Physical Chemistry · doi:10.1021/jp9610776 · Cited by 360 · see citing works
Davenport, A. P., Alexander, S. P. H., Sharman, J. L., Pawson, A. J., Benson, H. E., Monaghan, A. E., Liew, W. C., Mpamhanga, C. P., Bonner, T. I., Neubig, R. R., et al. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.007179 · Cited by 327 · see citing works
Rapid Context-Dependent Ligand Desolvation in Molecular Docking
Mysinger, M. M., & Shoichet, B. K. (2010) · Journal of Chemical Information and Modeling · doi:10.1021/ci100214a · Cited by 323 · see citing works
Self-citationNew Class IV Charge Model for Extracting Accurate Partial Charges from Wave Functions
Li, J., Zhu, T., Cramer, C. J., & Truhlar, D. G. (1998) · The Journal of Physical Chemistry A · doi:10.1021/jp972682r · Cited by 260 · see citing works
Regulation of inflammation by extracellular acidification and proton-sensing GPCRs
Okajima, F. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.07.022 · Cited by 198 · see citing works
Quantifying the Relationships among Drug Classes
Hert, J., Keiser, M. J., Irwin, J. J., Oprea, T. I., & Shoichet, B. K. (2008) · Journal of Chemical Information and Modeling · doi:10.1021/ci8000259 · Cited by 169 · see citing works
Self-citationCavasotto, C. N., Orry, A. J. W., Murgolo, N., Czarniecki, M., Kocsi, S. A., Hawes, B. E., O’Neill, K. A., Hine, H., Burton, M. S., Voigt, J. H., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm070759m · Cited by 167 · see citing works
Komarova, S. V., Pereverzev, A., Shum, J., Sims, S. M., & Dixon, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406874102 · Cited by 160 · see citing works
A public-private partnership to unlock the untargeted kinome
Knapp, S., Arruda, P., Blagg, J., Burley, S. K., Drewry, D. H., Edwards, A. M., Fabbro, D., Gillespie, P., Gray, N. S., Küster, B., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1113 · Cited by 141 · see citing works
Katritch, V., Rueda, M., Lam, P. C., Yeager, M. J., & Abagyan, R. A. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22507 · Cited by 141 · see citing works
Directed molecular evolution of DREADDs: a generic approach to creating next-generation RASSLs
Dong, S., Rogan, S. C., & Roth, B. L. (2010) · Nature Protocols · doi:10.1038/nprot.2009.239 · Cited by 140 · see citing works
Self-citationChung, S., Funakoshi, T., & Civelli, O. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707606 · Cited by 115 · see citing works
Saxena, H., Deshpande, D. A., Tiegs, B. C., Yan, H., Battafarano, R., Burrows, W., Damera, G., Panettieri, R., DuBose, T., An, S. S., et al. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01807.x · Cited by 111 · see citing works
Self-citationLi, H., Wang, D., Singh, L. S., Berk, M. P., Tan, H., Zhao, Z., Steinmetz, R. W., Kirmani, K., Wei, G., & Xu, Y. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005705 · Cited by 108 · see citing works
Clinical pharmacokinetics of lorazepam
Greenblatt, D. J., Schillings, R. T., Kyriakopoulos, A. A., Shader, R. I., Sisenwine, S. F., Knowles, J. A., & Ruelius, H. W. (1976) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt1976203329 · Cited by 107 · see citing works
Tomura, H., Wang, J.-Q., Komachi, M., Damirin, A., Mogi, C., Tobo, M., Kon, J., Misawa, N., Sato, K., & Okajima, F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505287200 · Cited by 103 · see citing works
Ferguson, F. M., Fedorov, O., Chaikuad, A., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401582c · Cited by 99 · see citing works
Onozawa, Y., Fujita, Y., Kuwabara, H., et al. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.03.007 · Cited by 97 · see citing works
Ovarian Cancer G Protein Coupled Receptor 1, a New Metastasis Suppressor Gene in Prostate Cancer
Singh, L. S., Berk, M. P., Oates, R., Zhao, Z., Tan, H., Jiang, Y., Zhou, A., Kirmani, K., Steinmetz, R., Lindner, D. J., et al. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm107 · Cited by 97 · see citing works
Evers, A., & Klebe, G. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200352776 · Cited by 93 · see citing works
Ichimonji, I., Tomura, H., Mogi, C., Sato, K., Aoki, H., Hisada, T., Dobashi, K., Ishizuka, T., Mori, M., & Okajima, F. (2010) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00415.2009 · Cited by 91 · see citing works
Roth, B. L., & Kroeze, W. K. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.654764 · Cited by 88 · see citing works
Self-citationFrick, K. K., Krieger, N. S., Nehrke, K. W., & Bushinsky, D. A. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081015 · Cited by 88 · see citing works
Yang, M., Mailhot, G., Birnbaum, M. J., MacKay, C. A., Mason‐Savas, A., & Odgren, P. R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602191200 · Cited by 85 · see citing works
Huang, X., Mangano, T. J., Hufeisen, S., Setola, V., & Roth, B. L. (2010) · Assay and Drug Development Technologies · doi:10.1089/adt.2010.0331 · Cited by 83 · see citing works
Self-citationMogi, C., Tomura, H., Tobo, M., Wang, J.-Q., Damirin, A., Kon, J., Komachi, M., Hashimoto, K., Sato, K., & Okajima, F. (2005) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fp0050599 · Cited by 76 · see citing works
Thompson, S. A., Wingrove, P. B., Connelly, L., Whiting, P. J., & Wafford, K. A. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.4.861 · Cited by 68 · see citing works
Russell, J. L., Goetsch, S. C., Aguilar, H. R., Coe, H., Luo, X., Liu, N., van Rooij, E., Frantz, D. E., & Schneider, J. W. (2012) · ACS Chemical Biology · doi:10.1021/cb300001m · Cited by 66 · see citing works
Mohebbi, N., Benabbas, C., Vidal, S., et al. (2012) · Cellular Physiology and Biochemistry · doi:10.1159/000338486 · Cited by 65 · see citing works
Kalk, P., Eggert, B., Relle, K., et al. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707319 · Cited by 63 · see citing works
Expression and Function of Proton-Sensing G-Protein-Coupled Receptors in Inflammatory Pain
Chen, Y., Huang, C.-W., Lin, C.-S., Chang, W., & Sun, W. (2009) · Molecular Pain · doi:10.1186/1744-8069-5-39 · Cited by 62 · see citing works
Gravius, A., Barberi, C., Schäfer, D., Schmidt, W., & Danysz, W. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.008 · Cited by 60 · see citing works
Functional expression of M1, M3 and M5 muscarinic acetylcholine receptors in yeast
Erlenbach, I., Kostenis, E., Schmidt, C. L., et al. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00344.x · Cited by 58 · see citing works
Matsuzaki, S., Ishizuka, T., Yamada, H., Kamide, Y., Hisada, T., Ichimonji, I., Aoki, H., Yatomi, M., Komachi, M., Tsurumaki, H., et al. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.08.087 · Cited by 58 · see citing works
Aoki, H., Mogi, C., Hisada, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079985 · Cited by 51 · see citing works
Li, J., Guo, B., Wang, J., et al. (2013) · Journal of Molecular Signaling · doi:10.1186/1750-2187-8-6 · Cited by 50 · see citing works
Daumas, S., Bétourné, A., Halley, H., Wolfer, D. P., Lipp, H.-P., Lassalle, J., & Francès, B. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.02.001 · Cited by 46 · see citing works
A‐kinase anchoring proteins regulate compartmentalized cAMP signaling in airway smooth muscle
Horvat, S., Deshpande, D. A., Yan, H., Panettieri, R. A., Codina, J., DuBose, T. D., Xin, W., Rich, T. C., & Penn, R. B. (2012) · The FASEB Journal · doi:10.1096/fj.11-201020 · Cited by 44 · see citing works
Self-citationLiu, J.-P., Komachi, M., Tomura, H., Mogi, C., Damirin, A., Tobo, M., Takano, M., Nochi, H., Tamoto, K., Sato, K., et al. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00977.2009 · Cited by 41 · see citing works
The role of CAMKIIα in neuropathic pain
Chen, Y., Yang, C., Luo, F., et al. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.01.167 · Cited by 35 · see citing works
Schneider, J. W., Goetsch, S. C., Leng, X., et al. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300025a · Cited by 32 · see citing works
Building alternate protein structures using the elastic network model
Yang, Q., & Sharp, K. A. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22184 · Cited by 23 · see citing works
Where will new neuroscience therapies come from?
Schoepp, D. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3559 · Cited by 22 · see citing works
Mogi, C., Nakakura, T., & Okajima, F. (2013) · Endocrine Journal · doi:10.1507/endocrj.ej13-0380 · Cited by 21 · see citing works
Wang, J.-Q., Sun, Y., Tomura, H., & Okajima, F. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.07.015 · Cited by 13 · see citing works
What makes lorazepam different from other benzodiazepines?
Pompéia, S., Manzano, G. M., Tufik, S., & Bueno, O. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.569005 · Cited by 8 · see citing works
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Roth, B. L. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.040 · Cited by 1,742 · see citing works
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Wacker, D., Stevens, R. C., & Roth, B. L. (2017) · Cell · doi:10.1016/j.cell.2017.07.009 · Cited by 560 · see citing works
Self-citationA practical guide to large-scale docking
Bender, B. J., Gahbauer, S., Luttens, A., Lyu, J., Webb, C. M., Stein, R. M., Fink, E. A., Balius, T. E., Carlsson, J., Irwin, J. J., et al. (2021) · Nature Protocols · doi:10.1038/s41596-021-00597-z · Cited by 546 · see citing works
“In the case of MRGPRX2 62 and GPR68 63 , for instance, the authors predicted multiple binding poses of a known active ligand and used mutagenesis and binding assays to test these predictions.”
BackgroundSelf-citationUnexplored therapeutic opportunities in the human genome
Oprea, T. I., Bologa, C. G., Brunak, S., Campbell, A., Gan, G. N., Gaulton, A., Gomez, S. M., Guha, R., Hersey, A., Holmes, J., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.14 · Cited by 378 · see citing works
Self-citationIn silico design of novel probes for the atypical opioid receptor MRGPRX2
Lansu, K., Karpiak, J., Liu, J., Huang, X.-P., McCorvy, J. D., Kroeze, W. K., Che, T., Nagase, H., Carroll, F. I., Jin, J., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2334 · Cited by 293 · see citing works
Self-citationStructures of the σ2 receptor enable docking for bioactive ligand discovery
Alon, A., Lyu, J., Braz, J. M., Tummino, T. A., Craik, V., O’Meara, M. J., Webb, C. M., Radchenko, D. S., Moroz, Y. S., Huang, X.-P., et al. (2021) · Nature · doi:10.1038/s41586-021-04175-x · Cited by 211 · see citing works
Self-citationG Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus
Riddy, D. M., Delerive, P., Summers, R. J., Sexton, P. M., & Langmead, C. J. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014373 · Cited by 108 · see citing works
Discovery of new GPCR ligands to illuminate new biology
Roth, B. L., Irwin, J. J., & Shoichet, B. K. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2490 · Cited by 94 · see citing works
Self-citationG-protein coupled receptors: advances in simulation and drug discovery
Miao, Y., & McCammon, J. A. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.06.008 · Cited by 93 · see citing works
Molecular basis of proton sensing by G protein-coupled receptors
Howard, M. K., Hoppe, N., Huang, X.-P., Mitrovic, D., Billesbølle, C. B., Macdonald, C. B., Mehrotra, E., Rockefeller Grimes, P., Trinidad, D. D., Delemotte, L., et al. (2025) · Cell · doi:10.1016/j.cell.2024.11.036 · Cited by 77 · see citing works
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- Authors
- Huang, X.-P., Karpiak, J., Kroeze, W. K., Zhu, H., Chen, X., Moy, S. S., Saddoris, K. A., Nikolova, V. D., Farrell, M. S., Wang, S., Mangano, T. J., Deshpande, D. A., Jiang, A., Penn, R. B., Jin, J., Koller, B. H., Kenakin, T., Shoichet, B. K., & Roth, B. L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California, San Francisco (US)
- Thomas Jefferson University (US)
- Corresponding author
- Shoichet, Brian K.
- Roth, Bryan L.
- ORCID
- Venue
- Nature
- Published
- 2015-11
- Volume
- 527
- Issue
- 7579
- Pages
- 477-483
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4796946
- OpenAlex
- W2125957493
- Cited by
- 284
- References
- 64
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 23 · 2023: 23 · 2022: 30 · 2021: 28 · 2020: 24 · 2019: 28 · 2018: 30 · 2017: 29 · 2016: 20 · 2015: 1
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (HL114471, GM71896, HD079124)
- Genentech
- National Institute on Aging (R01AG041265)
- National Heart, Lung, and Blood Institute (P01HL114471)
- National Institute of Mental Health (U19MH082441, U01MH104974, GM59957)
- National Institute on Drug Abuse (R01DA027170, R01DA017204)
- National Institute of General Medical Sciences (GM71896, GM59957, R01GM059957, R01GM071896)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD079124)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- GPR68, GPR65, orphan G protein-coupled receptor, allosteric modulators, lorazepam, positive allosteric modulators, negative allosteric modulators, allosteric agonists, fear conditioning, yeast-based screening, benzodiazepines, homology modeling
- MeSH terms
- Allosteric Regulation, Allosteric Site, Animals, Benzyl Alcohols, Conditioning, Classical, Fear, Female, Humans, Ligands, Lorazepam, Male, Memory, Models, Molecular, Anti-Anxiety Agents, Triazines, Signal Transduction, Mice, Knockout, Receptors, G-Protein-Coupled, Mice, Drug Discovery, HEK293 Cells
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