The DOI matches its Crossref record; 92 of the 92 references it cites were found in a registry or an index.
Structures of the σ2 receptor enable docking for bioactive ligand discovery
Open accessPublished version of a preprint
Abstract
The σ 2 receptor has attracted intense interest in cancer imaging 1, psychiatric disease 2, neuropathic pain 3-5 and other areas of biology 6,7. Here we determined the crystal structure of this receptor in complex with the clinical candidate roluperidone 2 and the tool compound PB28 8. These structures templated a large-scale docking screen of 490 million virtual molecules, of which 484 compounds were synthesized and tested. We identified 127 new chemotypes with affinities superior to 1 μM, 31 of which had affinities superior to 50 nM. The hit rate fell smoothly and monotonically with docking score. We optimized three hits for potency and selectivity, and achieved affinities that ranged from 3 to 48 nM, with up to 250-fold selectivity versus the σ 1 receptor. Crystal structures of two ligands bound to the σ 2 receptor confirmed the docked poses. To investigate the contribution of the σ 2 receptor in pain, two potent σ 2-selective ligands and one potent σ 1/σ 2 non-selective ligand were tested for efficacy in a mouse model of neuropathic pain. All three ligands showed time-dependent decreases in mechanical hypersensitivity in the spared nerve injury model 9, suggesting that the σ 2 receptor has a role in nociception. This study illustrates the opportunities for rapid discovery of in vivo probes through structure-based screens of ultra large libraries, enabling study of underexplored areas of biology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The crystal structure of TMEM97, although bovine, was resolved in 2021 which illuminated the docking sites of small molecule S2R ligands, PB28, and roluperidone [63]”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [63]
In the citing paper
“The ligand binding site described for 20(S)-OHC in this model is remarkably consistent with the ligand-bound crystal structure of S2R, recently reported for S2R in complex with synthetic S2R ligands [63].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Wickham, H. (2016) · Use R! · doi:10.1007/978-3-319-24277-4 · Cited by 34,873
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Wickham, H., Averick, M., Bryan, J., Chang, W., McGowan, L., François, R., Grolemund, G., Hayes, A., Henry, L., Hester, J., et al. (2019) · Journal of Open Source Software · doi:10.21105/joss.01686 · Cited by 22,138
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047337 · Cited by 16,463
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,961
Wickham, H. (2016) · Use R! · doi:10.1007/978-3-319-24277-4_9 · Cited by 12,675
brms : An R Package for Bayesian Multilevel Models Using Stan
Bürkner, P.-C. (2017) · Journal of Statistical Software · doi:10.18637/jss.v080.i01 · Cited by 9,476
Liebschner, D., Afonine, P. V., Baker, M. L., Bunkóczi, G., Chen, V. B., Croll, T. I., Hintze, B., Hung, L.-W., Jain, S., McCoy, A. J., et al. (2019) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319011471 · Cited by 7,953
Stan : A Probabilistic Programming Language
Carpenter, B., Gelman, A., Hoffman, M. D., Lee, D., Goodrich, B., Betancourt, M., Brubaker, M., Guo, J., Li, P., & Riddell, A. (2017) · Journal of Statistical Software · doi:10.18637/jss.v076.i01 · Cited by 7,754
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,740
T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. Thornton
Notredame, C., Higgins, D. G., & Heringa, J. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4042 · Cited by 6,964
A new force field for molecular mechanical simulation of nucleic acids and proteins
Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Profeta, S., & Weiner, P. K. (1984) · Journal of the American Chemical Society · doi:10.1021/ja00315a051 · Cited by 4,641
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., O’Meara, M. J., Rezelj, V. V., Guo, J. Z., Swaney, D. L., et al. (2020) · Nature · doi:10.1038/s41586-020-2286-9 · Cited by 4,405
Self-citationA Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core
Zimmermann, L., Stephens, A., Nam, S.-Z., Rau, D., Kübler, J., Lozajic, M., Gabler, F., Söding, J., Lupas, A. N., & Alva, V. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.12.007 · Cited by 2,522
OPM database and PPM web server: resources for positioning of proteins in membranes
Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I., & Lomize, A. L. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr703 · Cited by 2,126
Crystal structure of the µ-opioid receptor bound to a morphinan antagonist
Manglik, A., Kruse, A. C., Kobilka, T. S., Thian, F. S., Mathiesen, J. M., Sunahara, R. K., Pardo, L., Weis, W. I., Kobilka, B. K., & Granier, S. (2012) · Nature · doi:10.1038/nature10954 · Cited by 1,400
Self-citationUltra-large library docking for discovering new chemotypes
Lyu, J., Wang, S., Balius, T. E., Singh, I., Levit, A., Moroz, Y. S., O’Meara, M. J., Che, T., Algaa, E., Tolmachova, K., et al. (2019) · Nature · doi:10.1038/s41586-019-0917-9 · Cited by 998
Self-citationAutomated docking with grid‐based energy evaluation
Meng, E. C., Shoichet, B. K., & Kuntz, I. D. (1992) · Journal of Computational Chemistry · doi:10.1002/jcc.540130412 · Cited by 949
Self-citationR-squared for Bayesian Regression Models
Gelman, A., Goodrich, B., Gabry, J., & Vehtari, A. (2018) · The American Statistician · doi:10.1080/00031305.2018.1549100 · Cited by 924
Purification, molecular cloning, and expression of the mammalian sigma1-binding site.
Hanner, M., Moebius, F. F., Flandorfer, A., Knaus, H. G., Striessnig, J., Kempner, E. S., & Glossmann, H. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.8072 · Cited by 914
Automated 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
Self-citationPRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome
Kroeze, W. K., Sassano, M. F., Huang, X.-P., Lansu, K., McCorvy, J. D., Giguère, P. M., Sciaky, N., & Roth, B. L. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3014 · Cited by 755
Self-citationCrystallizing membrane proteins using lipidic mesophases
Caffrey, M., & Cherezov, V. (2009) · Nature Protocols · doi:10.1038/nprot.2009.31 · Cited by 677
Polder maps: improving OMIT maps by excluding bulk solvent
Liebschner, D. C., Afonine, P. V., Moriarty, N. W., Poon, B. K., Sobolev, O. V., Terwilliger, T. C., & Adams, P. D. (2017) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798316018210 · Cited by 675
Pharmacogenomics of GPCR Drug Targets
Hauser, A. S., Chavali, S., Masuho, I., Jahn, L. J., Martemyanov, K. A., Gloriam, D. E. I., & Babu, M. M. (2017) · Cell · doi:10.1016/j.cell.2017.11.033 · Cited by 637
Transient Mammalian Cell Transfection with Polyethylenimine (PEI)
Longo, P. A., Kavran, J. M., Kim, S. K., & Leahy, D. J. (2013) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-418687-3.00018-5 · Cited by 590
Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone
Wang, S., Che, T., Levit, A., Shoichet, B. K., Wacker, D., & Roth, B. L. (2018) · Nature · doi:10.1038/nature25758 · Cited by 498
Self-citationSigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines.
Vilner, B. J., John, C. S., & Bowen, W. D. (1995) · PubMed · Cited by 482
Crystal structure of the human σ1 receptor
Schmidt, H. R., Zheng, S., Gurpinar, E., Koehl, A., Manglik, A., & Kruse, A. C. (2016) · Nature · doi:10.1038/nature17391 · Cited by 482
Self-citationDissociation of the Opioid Receptor Mechanisms that Control Mechanical and Heat Pain
Scherrer, G., Imamachi, N., Cao, Y. Q., Contet, C., Mennicken, F., O’Donnell, D., Kieffer, B. L., & Basbaum, A. I. (2009) · Cell · doi:10.1016/j.cell.2009.04.019 · Cited by 463
Self-citationImpact of GPCR Structures on Drug Discovery
Congreve, M., de Graaf, C., Swain, N. A., & Tate, C. G. (2020) · Cell · doi:10.1016/j.cell.2020.03.003 · Cited by 393
Hellewell, S. B., Bruce, A., Feinstein, G., Orringer, J., Williams, W., & Bowen, W. D. (1994) · European Journal of Pharmacology: Molecular Pharmacology · doi:10.1016/0922-4106(94)90115-5 · Cited by 390
Mahdessian, H., Taxiarchis, A., Popov, S., Silveira, A., Franco-Cereceda, A., Hamsten, A., Eriksson, P., & van't Hooft, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323785111 · Cited by 369
tidybayes: Tidy Data and Geoms for Bayesian Models
Kay, M. (2018) · Figshare · doi:10.5281/zenodo.1308151 · Cited by 353
GPCRdb in 2021: integrating GPCR sequence, structure and function
Kooistra, A. J., Mordalski, S., Pándy-Szekeres, G., Esguerra, M., Mamyrbekov, A., Munk, C., Keserű, G. M., & Gloriam, D. E. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1080 · Cited by 351
Hellewell, S. B., & Bowen, W. D. (1990) · Brain Research · doi:10.1016/0006-8993(90)91143-5 · Cited by 341
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 325
Self-citationSpared nerve injury model of neuropathic pain in the mouse: a behavioral and anatomic analysis
Shields, S. D., Eckert, W. A., & Basbaum, A. I. (2003) · Journal of Pain · doi:10.1067/s1526-5900(03)00781-8 · Cited by 322
Self-citationVirtual discovery of melatonin receptor ligands to modulate circadian rhythms
Stein, R. M., Kang, H. J., McCorvy, J. D., Glatfelter, G. C., Jones, A., Che, T., Slocum, S. T., Huang, X., Savych, O., Moroz, Y. S., et al. (2020) · Nature · doi:10.1038/s41586-020-2027-0 · Cited by 312
Self-citationAllosteric ligands for the pharmacologically dark receptors GPR68 and GPR65
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., et al. (2015) · Nature · doi:10.1038/nature15699 · Cited by 284
Self-citationIdentification of the gene that codes for the σ 2 receptor
Alon, A., Schmidt, H. R., Wood, M. D., Sahn, J. J., Martin, S. F., & Kruse, A. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705154114 · Cited by 267
Self-citationDecision Making in Structure-Based Drug Discovery: Visual Inspection of Docking Results
Fischer, A., Smieško, M., Sellner, M. S., & Lill, M. A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02227 · Cited by 250
Structure-Based Discovery of A 2A Adenosine Receptor Ligands
Carlsson, J., Yoo, L. S., Gao, Z.-G., Irwin, J. J., Shoichet, B. K., & Jacobson, K. A. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100240h · Cited by 233
Self-citationAccumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination
Hubler, Z., Allimuthu, D., Bederman, I., Elitt, M. S., Madhavan, M., Allan, K. C., Shick, H. E., Garrison, E., T. Karl, M., Factor, D. C., et al. (2018) · Nature · doi:10.1038/s41586-018-0360-3 · Cited by 226
Schuller, M., Correy, G. J., Gahbauer, S., Fearon, D., Wu, T., Díaz, R. E., Young, I. D., Martins, L. C., Smith, D. H., Schulze‐Gahmen, U., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf8711 · Cited by 205
Self-citationIdentification of Cholesterol-Regulating Genes by Targeted RNAi Screening
Bartz, F., Kern, L., Erz, D., Zhu, M., Gilbert, D., Meinhof, T., Wirkner, U., Erfle, H., Muckenthaler, M., Pepperkok, R., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.05.009 · Cited by 198
Romero, L. I., Zamanillo, D., Nadal, X., Sánchez-Arroyos, R., Rivera‐Arconada, I., Dordal, A., Montero, A., Muro, A., Bura, A., Segalés, C., et al. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01942.x · Cited by 185
The Molecular Function of σ Receptors: Past, Present, and Future
Schmidt, H. R., & Kruse, A. C. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.07.006 · Cited by 177
Self-citationAdvances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment: Meeting New Challenges
Kufareva, I., Katritch, V., Stevens, R. C., & Abagyan, R. A. (2014) · Structure · doi:10.1016/j.str.2014.06.012 · Cited by 169
Generation and phenotypic analysis of sigma receptor type I (σ1) knockout mice
Langa, F., Codony, X., Tovar, V., Lavado, A., Giménez, E., Cozar, P., Cantero, M., Dordal, A., Hernández, E., Pérez, R., et al. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02950.x · Cited by 167
de la Puente, B., Nadal, X., Portillo-Salido, E. F., Sánchez-Arroyos, R., Ovalle, S., Palacios, G., Muro, A., Romero, L. I., Entrena, J. M., Baeyens, J. M., et al. (2009) · Pain · doi:10.1016/j.pain.2009.05.013 · Cited by 166
Potential applications for sigma receptor ligands in cancer diagnosis and therapy
van Waarde, A., Rybczynska, A. A., Ramakrishnan, N. K., Ishiwata, K., Elsinga, P. H., & Dierckx, R. (2014) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.08.022 · Cited by 158
An Integrated Framework Advancing Membrane Protein Modeling and Design
Alford, R. F., Leman, J. K., Weitzner, B. D., Duran, A. M., Tilley, D. C., Elazar, A., & Gray, J. J. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004398 · Cited by 154
Riad, A., Zeng, C., Weng, C.-C., Winters, H., Xu, K., Makvandi, M., Metz, T., Carlin, S., & Mach, R. H. (2018) · Scientific Reports · doi:10.1038/s41598-018-35430-3 · Cited by 147
Property-Unmatched Decoys in Docking Benchmarks
Stein, R. M., Ying, Y., Balius, T. E., O’Meara, M. J., Lyu, J., Young, J., Tang, K. G., Shoichet, B. K., & Irwin, J. J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00598 · Cited by 143
Self-citationFormalin-induced pain is reduced in σ1 receptor knockout mice
Cendán, C. M., Pujalte, J. M., Portillo-Salido, E. F., Montoliu, L., & Baeyens, J. M. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.01.036 · Cited by 141
Electrostatic Contributions to Heat Capacity Changes of DNA-Ligand Binding
Gallagher, K., & Sharp, K. A. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77566-6 · Cited by 135
Exploiting Ordered Waters in Molecular Docking
Huang, N., & Shoichet, B. K. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8006239 · Cited by 133
Self-citationBruna, J., Videla, S., Argyriou, A. A., Velasco, R., Villoria, J., Santos, C., Nadal, C., Cavaletti, G., Alberti, P., Briani, C., et al. (2017) · Neurotherapeutics · doi:10.1007/s13311-017-0572-5 · Cited by 124
Azzariti, A., Colabufo, N. A., Berardi, F., Porcelli, L., Niso, M., Simone, G. M., Perrone, R., & Paradiso, A. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0402 · Cited by 112
Davidson, M., Saoud, J. B., Staner, C., Noël, N., Luthringer, E., Werner, S., Reilly, J. G., Schaffhauser, J.-Y., Rabinowitz, J., Weiser, M., et al. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17010122 · Cited by 104
Ebrahimi‐Fakhari, D., Wahlster, L., Bartz, F., Werenbeck-Ueding, J., Praggastis, M., Zhang, J., Joggerst-Thomalla, B., Theiß, S., Grimm, D., Ory, D. S., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw204 · Cited by 99
Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice
Sahn, J. J., Mejia, G. L., Ray, P. R., Martin, S. F., & Price, T. J. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00200 · Cited by 98
Grundman, M., Morgan, R., Lickliter, J. D., Schneider, L. S., DeKosky, S., Izzo, N. J., Guttendorf, R., Higgin, M., Pribyl, J., Mozzoni, K., et al. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.11.001 · Cited by 96
Solórzano, C., Villafuerte, D. B., Meda, K., Cevikbas, F., Braz, J. M., Sharif‐Naeini, R., Juarez-Salinas, D. L., Llewellyn‐Smith, I. J., Guan, Z., & Basbaum, A. I. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2955-14.2015 · Cited by 89
Self-citationAntinociceptive effects of haloperidol and its metabolites in the formalin test in mice
Cendán, C. M., Pujalte, J. M., Portillo-Salido, E. F., & Baeyens, J. M. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0127-z · Cited by 87
Negri, A., Rives, M., Caspers, M. J., Prisinzano, T. E., Javitch, J. A., & Filizola, M. (2013) · Journal of Chemical Information and Modeling · doi:10.1021/ci400019t · Cited by 66
Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition
Long, T., Hassan, A., Thompson, B. M., McDonald, J. G., Wang, J., & Li, X. (2019) · Nature Communications · doi:10.1038/s41467-019-10279-w · Cited by 65
Vázquez‐Rosa, E., Watson, M. R., Sahn, J. J., Hodges, T. R., Schroeder, R. E., Cintrón-Pérez, C. J., Shin, M., Yin, T. C., Emery, J. L., Martin, S. F., et al. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00543 · Cited by 64
TM6SF2 and MAC30, new enzyme homologs in sterol metabolism and common metabolic disease
Sanchez-Pulido, L., & Ponting, C. P. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00439 · Cited by 63
Ligand Strain Energy in Large Library Docking
Gu, S., Smith, M. S., Ying, Y., Irwin, J. J., & Shoichet, B. K. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00368 · Cited by 62
Self-citationDocking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson’s Disease
Jaiteh, M., Zeifman, A. A., Saarinen, M., Svenningsson, P., Brea, J. M., Loza, M. I., & Carlsson, J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00204 · Cited by 61
Emerging structural biology of lipid G protein‐coupled receptors
Audet, M., & Stevens, R. C. (2018) · Protein Science · doi:10.1002/pro.3509 · Cited by 55
Investigational sigma-1 receptor antagonists for the treatment of pain
Vela, J. M., Merlos, M., & Almansa, C. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1048334 · Cited by 54
Structure-based discovery of potent and selective melatonin receptor agonists
Patel, N., Huang, X., Grandner, J. M., Johansson, L. C., Stauch, B., McCorvy, J. D., Liu, Y., Roth, B. L., & Katritch, V. (2020) · eLife · doi:10.7554/elife.53779 · Cited by 50
Self-citationIntagliata, S., Sharma, A., King, T. I., Mésangeau, C., Seminerio, M. J., Chin, F. T., Wilson, L., Matsumoto, R. R., McLaughlin, J. P., Avery, B. A., et al. (2020) · The AAPS Journal · doi:10.1208/s12248-020-00472-x · Cited by 50
Selectivity Challenges in Docking Screens for GPCR Targets and Antitargets
Weiss, D. R., Karpiak, J. D., Huang, X., Sassano, M. F., Lyu, J., Roth, B. L., & Shoichet, B. K. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00718 · Cited by 46
Self-citationSmall molecule modulators of σ2R/Tmem97 reduce alcohol withdrawal-induced behaviors
Scott, L. L., Sahn, J. J., Ferragud, A., Yen, R. C., Satarasinghe, P., Wood, M. D., Hodges, T. R., Shi, T., Prakash, B. A., Friese, K. M., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0067-z · Cited by 42
Schuller, M., Correy, G. J., Gahbauer, S., Fearon, D., Wu, T., Díaz, R. E., Young, I. D., Martins, L. C., Smith, D. H., Schulze‐Gahmen, U., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.24.393405 · Cited by 38
Self-citationNew σ and 5-HT1A Receptor Ligands: ω-(Tetralin-1-yl)-n-alkylamine Derivatives
Berardi, F., Colabufo, N. A., Giudice, G. D., Perrone, R., Tortorella, V., Govoni, S. M., & Lucchi, L. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm950409c · Cited by 34
Quadir, S. G., Tanino, S. M., Rohl, C. D., Sahn, J. J., Yao, E. J., Cruz, L. R., Cottone, P., Martin, S. F., & Sabino, V. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108409 · Cited by 33
Simplified LC-MS Method for Analysis of Sterols in Biological Samples
Skubic, C., Vovk, I., Rozman, D., & Križman, M. (2020) · Molecules · doi:10.3390/molecules25184116 · Cited by 31
Nastasi, G., Miceli, C., Pittalà, V., Modica, M. N., Prezzavento, O., Romeo, G., Rescifina, A., Marrazzo, A., & Amata, E. (2017) · Journal of Cheminformatics · doi:10.1186/s13321-017-0191-5 · Cited by 31
Harvey, P. D., Saoud, J. B., Luthringer, R., Moroz, S., Blazhevych, Y., Ștefănescu, C., & Davidson, M. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.08.029 · Cited by 31
Keefe, R. S. E., Harvey, P. D., Khan, A., Saoud, J. B., Staner, C., Davidson, M., & Luthringer, R. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.17m11753 · Cited by 30
Abate, C., Niso, M., Abatematteo, F. S., Contino, M., Colabufo, N. A., & Berardi, F. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.589810 · Cited by 30
Chu, U. B., & Ruoho, A. E. (2015) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0134s71 · Cited by 27
Muralidharan, A., Samoshkin, A., Convertino, M., Piltonen, M., Gris, P., Wang, J., Jiang, C., Klares, R., Linton, A. A., Ji, R., et al. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15463 · Cited by 5
Research works printed but not linked: 1
- Kabsch, W. XDS. Acta Crystallogr. D 66,132 (2010).
Cited by
Sorted by citations
Computational approaches streamlining drug discovery
Sadybekov, A., & Katritch, V. (2023) · Nature · doi:10.1038/s41586-023-05905-z · Cited by 1,424
A 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
Self-citationThe Art and Science of Molecular Docking
Paggi, J. M., Pandit, A., & Dror, R. O. (2024) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-030222-120000 · Cited by 546
ZINC-22─A Free Multi-Billion-Scale Database of Tangible Compounds for Ligand Discovery
Tingle, B. I., Tang, K. G., Castanon, M., Gutierrez, J. J., Khurelbaatar, M., Dandarchuluun, C., Moroz, Y. S., & Irwin, J. J. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.2c01253 · Cited by 314
Self-citationModeling the expansion of virtual screening libraries
Lyu, J., Irwin, J. J., & Shoichet, B. K. (2023) · Nature Chemical Biology · doi:10.1038/s41589-022-01234-w · Cited by 193
Self-citation
Metadata
- Authors
- 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., Liu, Y., Roth, B. L., Irwin, J. J., Basbaum, A. I., Shoichet, B. K., & Kruse, A. C.
- Affiliations
- Harvard University (US)
- University of California, San Francisco (US)
- University of Michigan (US)
- Taras Shevchenko National University of Kyiv (UA)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Basbaum, Allan I.
- Shoichet, Brian K.
- Kruse, Andrew C.
- ORCID
- Venue
- Nature
- Published
- 2021-12-08
- Volume
- 600
- Issue
- 7890
- Pages
- 759-764
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8867396
- OpenAlex
- W4200289210
- Cited by
- 211
- References
- 92
- Citations by year
- 2026: 24 · 2025: 41 · 2024: 49 · 2023: 55 · 2022: 37 · 2021: 5
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐ AC02‐06CH11357, Contract No. DE-AC02-06CH11357., AC02‐06CH11357, 06CH11357, No. DE-AC02-06CH11357, DE-AC02-)
- Sanofi
- Vallee Foundation
- National Institutes of Health (ACB-12002, 1s10od012289-01a1, DE-AC02–06CH11357, AGM-12006)
- Defense Advanced Research Projects Agency (HR0011, HR0011-19-2-0020)
- Office of Science (Contract No. DE-AC02-06CH11357, AC02‐06CH11357, DE-AC02, No. DE-AC02-06CH11357., 06CH11357, DE-AC02-06CH11357)
- National Cancer Institute (DE-AC02-06CH11357, ACB12002, AGM-12006)
- National Institute of General Medical Sciences (S10 OD012289, R01GM133836, R01GM119185, P41GM103311, DE-AC02-06CH11357, AGM-12006, ACB-12002, T32GM007175, P30GM138396, R35GM122481, AGM-12006, P30GM138396)
- National Institute of Neurological Disorders and Stroke (R35NS097306)
- Argonne National Laboratory (DE- AC02-06-CH11357, DE-AC02, AC02–06CH11357, No. DE-AC02-06CH11357, 06CH11357, Contract No. DE-AC02-06CH11357., S10 OD012289)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Keywords
- sigma-2 receptor, crystal structure, virtual screening, structure-based drug design, protein-ligand docking, neuropathic pain, mechanical hypersensitivity, spared nerve injury model, nociception
- MeSH terms
- Animals, Ligands, Neuralgia, Structure-Activity Relationship, Receptors, sigma, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
