Discovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain
Open accessAbstract
Endocannabinoids are lipid signaling molecules that regulate a wide range of mammalian behaviors, including pain, inflammation, and cognitive/emotional state. The endocannabinoid anandamide is principally degraded by the integral membrane enzyme fatty acid amide hydrolase (FAAH), and there is currently much interest in developing FAAH inhibitors to augment endocannabinoid signaling in vivo. Here, we report the discovery and detailed characterization of a highly efficacious and selective FAAH inhibitor, PF-3845. Mechanistic and structural studies confirm that PF-3845 is a covalent inhibitor that carbamylates FAAH's serine nucleophile. PF-3845 selectively inhibits FAAH in vivo, as determined by activity-based protein profiling; raises brain anandamide levels for up to 24 hr; and produces significant cannabinoid receptor-dependent reductions in inflammatory pain. These data thus designate PF-3845 as a valuable pharmacological tool for in vivo characterization of the endocannabinoid system.
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
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?
FAAH inhibition attenuates mechanically-induced pain in the CFA model of inflammatory pain.
“FAAH inhibition attenuates mechanically-induced pain in the CFA model of inflammatory pain (Ahn et al, 2009(Ahn et al, , 2011;;Jayamanne et al, 2006;Sasso et al, 2012).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ahn et al, 2009
Brain levels of 2-AG are approximately three orders of magnitude higher than AEA brain levels.
“It is important to note that brain levels of 2-AG are approximately three orders of magnitude higher than AEA brain levels (Ahn et al, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ahn et al, 2009
The disparity in tolerance development in mice treated repeatedly with a MAGL inhibitor versus a FAAH inhibitor may be related to differences in mass action of these endocannabinoids.
“Thus, the disparity in tolerance development in mice treated repeatedly with a MAGL inhibitor vs a FAAH inhibitor may be related to differences in mass action of these endocannabinoids.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Ahn et al, 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Efficient Analysis of Experimental Observations
Dixon, W. J. (1980) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.20.040180.002301 · Cited by 2,216 · see citing works
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125 · see citing works
Self-citationThe Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310 · see citing works
Self-citationModulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293 · see citing works
A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol
Blankman, J. L., Simon, G. M., & Cravatt, B. F. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.11.006 · Cited by 1,177 · see citing works
Self-citationActivity-based protein profiling: The serine hydrolases
Liu, Y., Patricelli, M. P., & Cravatt, B. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14694 · Cited by 1,133 · see citing works
Self-citationSpeers, A. E., Adam, G. C., & Cravatt, B. F. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034490h · Cited by 955 · see citing works
Self-citationSelective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
Long, J. Z., Li, W., Booker, L., Burston, J. J., Kinsey, S. G., Schlosburg, J. E., Pavón, F. J., Serrano, A., Selley, D. E., Parsons, L. H., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.129 · Cited by 938 · see citing works
Self-citationProfiling Enzyme Activities In Vivo Using Click Chemistry Methods
Speers, A. E., & Cravatt, B. F. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.03.012 · Cited by 774 · see citing works
Self-citationStructure and function of fatty acid amide hydrolase
McKinney, M. K., & Cravatt, B. F. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133450 · Cited by 680 · see citing works
Self-citationGobbi, G., Bambico, F. R., Mangieri, R. A., Bortolato, M., Campolongo, P., Solinas, M., Cassano, T., Morgese, M. G., Debonnel, G., Duranti, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509591102 · Cited by 676 · see citing works
C-h⋯π-interactions in proteins
Brandl, M., Weiss, M. S., Jabs, A., Sühnel, J., & Hilgenfeld, R. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4473 · Cited by 643 · see citing works
Enzymatic pathways that regulate endocannabinoid signaling in the nervous system
Ahn, K., McKinney, M. K., & Cravatt, B. F. (2008) · Chemical Reviews · doi:10.1021/cr0782067 · Cited by 529 · see citing works
Self-citationStructural Adaptations in a Membrane Enzyme That Terminates Endocannabinoid Signaling
Bracey, M. H., Hanson, M. A., Masuda, K. R., Stevens, R. C., & Cravatt, B. F. (2002) · Science · doi:10.1126/science.1076535 · Cited by 490 · see citing works
Self-citationThe endogenous cannabinoid system protects against colonic inflammation
Massa, F., Marsicano, G., Hermann, H., Cannich, A., Monory, K., Cravatt, B. F., Ferri, G., Sibaev, A., Storr, M., & Lutz, B. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19465 · Cited by 461 · see citing works
Self-citationFegley, D., Gaetani, S., Duranti, A., Tontini, A., Mor, M., Tarzia, G., & Piomelli, D. (2005) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.078980 · Cited by 427 · see citing works
Biochemical mechanisms of drug action: what does it take for success?
Swinney, D. C. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1500 · Cited by 396 · 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
Self-citationThe endogenous cannabinoid system protects against colonic inflammation
Massa, F., Marsicano, G., Hermann, H., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200419465 · Cited by 387 · see citing works
A Second Fatty Acid Amide Hydrolase with Variable Distribution among Placental Mammals
Wei, B. Q., Mikkelsen, T. S., McKinney, M. K., Lander, E. S., & Cravatt, B. F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606646200 · Cited by 361 · see citing works
Self-citationLeung, D., Saghatelian, A., Simon, G. M., & Cravatt, B. F. (2006) · Biochemistry · doi:10.1021/bi060163l · Cited by 348 · see citing works
Self-citationLichtman, A. H., Leung, D., Shelton, C. C., Saghatelian, A., Hardouin, C., Boger, D. L., & Cravatt, B. F. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.069401 · Cited by 329 · see citing works
Self-citationTsuboi, K., Sun, Y.-X., Okamoto, Y., Araki, N., Tonai, T., & Ueda, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413473200 · Cited by 328 · see citing works
Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling
Saghatelian, A., Trauger, S. A., Want, E. J., Hawkins, E. G., Siuzdak, G. E., & Cravatt, B. F. (2004) · Biochemistry · doi:10.1021/bi0480335 · Cited by 318 · see citing works
Self-citationEndocannabinoids: synthesis and degradation
Marzo, V. D. (2006) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_0505 · Cited by 308 · see citing works
Lichtman, A. H., Shelton, C. C., Advani, T., & Cravatt, B. F. (2004) · Pain · doi:10.1016/j.pain.2004.01.022 · Cited by 301 · see citing works
Self-citationThe Palmitoylethanolamide Family: A New Class of Anti-Inflammatory Agents ?
Lambert, D. M., Vandevoorde, S., Jonsson, K., & Fowler, C. J. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023370707 · Cited by 300 · see citing works
Actions of the FAAH inhibitor URB597 in neuropathic and inflammatory chronic pain models
Jayamanne, A., Greenwood, R., Mitchell, V. A., Aslan, S., Piomelli, D., & Vaughan, C. W. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706510 · Cited by 287 · see citing works
Moreira, F. A., Kaiser, N., Monory, K., & Lutz, B. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.07.005 · Cited by 282 · see citing works
Boger, D. L., Sato, H., Lerner, A. E., Hedrick, M. P., Fecik, R. A., Miyauchi, H., Wilkie, G. D., Austin, B. J., Patricelli, M. P., & Cravatt, B. F. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5044 · Cited by 272 · see citing works
Self-citationAlexander, J. P., & Cravatt, B. F. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.08.011 · Cited by 226 · see citing works
Self-citationFunctional disassociation of the central and peripheral fatty acid amide signaling systems
Cravatt, B. F., Saghatelian, A., Hawkins, E. G., Clement, A. B., Bracey, M. H., & Lichtman, A. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401292101 · Cited by 225 · see citing works
Self-citationMethyl arachidonyl fluorophosphonate: a potent irreversible inhibitor of anandamide amidase
Deutsch, D. G., Omeir, R. L., Arreaza, G., Salehani, D., Prestwich, G. D., Huang, Z., & Howlett, A. C. (1997) · Biochemical Pharmacology · doi:10.1016/s0006-2952(96)00830-1 · Cited by 217 · see citing works
Novel Mechanistic Class of Fatty Acid Amide Hydrolase Inhibitors with Remarkable Selectivity
Ahn, K., Johnson, D. S., Fitzgerald, L. R., Liimatta, M. B., Arendse, A., Stevenson, T. I., Lund, E. T., Nugent, R. A., Nomanbhoy, T. K., Alexander, J. P., et al. (2007) · Biochemistry · doi:10.1021/bi701378g · Cited by 217 · see citing works
Self-citationInhibitors of arachidonoyl ethanolamide hydrolysis.
Koutek, B., Prestwich, G. D., Howlett, A. C., Chin, S. A., Salehani, D., Akhavan, N., & Deutsch, D. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31599-5 · Cited by 202 · see citing works
Cellular accumulation of anandamide: consensus and controversy
Hillard, C. J., & Jarrahian, A. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705468 · Cited by 199 · see citing works
Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality
Naidu, P. S., Varvel, S. A., Ahn, K., Cravatt, B. F., Martin, B. R., & Lichtman, A. H. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0689-4 · Cited by 184 · see citing works
Self-citationRusso, R., LoVerme, J., La Rana, G., Compton, T. R., Parrott, J., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Calignano, A., et al. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.119941 · Cited by 182 · see citing works
Proteomic analysis of Fasciola hepatica excretory-secretory products
Jefferies, J. R., Campbell, A. M., van Rossum, A. J., Barrett, J., & Brophy, P. M. (2001) · PROTEOMICS · doi:10.1002/1615-9861(200109)1:9 · Cited by 171 · see citing works
Holt, S., Comelli, F., Costa, B., & Fowler, C. J. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706348 · Cited by 168 · see citing works
Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms
Chang, L., Luo, L., Palmer, J. A., Sutton, S. W., Wilson, S. J., Barbier, A., Breitenbucher, J. G., Chaplan, S. R., & Webb, M. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706773 · Cited by 166 · see citing works
Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms
Chang, L., Luo, L., Palmer, J. A., Sutton, S., Wilson, S. J., Barbier, A. J., Breitenbucher, J. G., Chaplan, S. R., & Webb, M. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706699 · Cited by 155 · see citing works
Structure-guided inhibitor design for human FAAH by interspecies active site conversion
Mileni, M., Johnson, D. S., Wang, Z., Everdeen, D. S., Liimatta, M. B., Pabst, B. A., Bhattacharya, K., Nugent, R. A., Kamtekar, S., Cravatt, B. F., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806121105 · Cited by 154 · see citing works
Self-citationPatricelli, M. P., Lovato, M. A., & Cravatt, B. F. (1999) · Biochemistry · doi:10.1021/bi990637z · Cited by 148 · see citing works
Self-citationAnandamide transport: A critical review
Glaser, S. T., Kaczocha, M., & Deutsch, D. G. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.05.007 · Cited by 144 · see citing works
Marzo, V. D., Bisogno, T., & PETROCELLIS, L. D. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.05.014 · Cited by 116 · see citing works
Activation of the endocannabinoid system by organophosphorus nerve agents
Nomura, D. K., Blankman, J. L., Simon, G. M., Fujioka, K., Issa, R. S., Ward, A. M., Cravatt, B. F., & Casida, J. E. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.86 · Cited by 112 · see citing works
Self-citationBoger, D. L., Sato, H., Lerner, A. E., et al. (1999) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(98)00734-3 · Cited by 108 · see citing works
Zhang, D., Saraf, A., Kolasa, T., Bhatia, P., Zheng, G. Z., Patel, M., Lannoye, G. S., Richardson, P., Stewart, A., Rogers, J. C., et al. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.11.009 · Cited by 99 · see citing works
The Pharmacohistory of Cannabis Sativa
Mechoulam, R. (2019) · Chapman & Hall/CRC eBooks · doi:10.1201/9780429260667-1 · Cited by 92 · see citing works
McFarland, M. J., & Barker, E. L. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.07.008 · Cited by 91 · see citing works
Thiadiazolopiperazinyl ureas as inhibitors of fatty acid amide hydrolase
Keith, J. M., Apodaca, R. L., Xiao, W., Seierstad, M. J., Pattabiraman, K., Wu, J., Webb, M., Karbarz, M. J., Brown, S. M., Wilson, S. M. B., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.081 · Cited by 90 · see citing works
Fowler, C. J. (2006) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2006.00442.x · Cited by 57 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The resurgence of covalent drugs
Singh, J., Petter, R. C., Baillie, T. A., & Whitty, A. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3410 · Cited by 1,873 · see citing works
Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system
Schlosburg, J. E., Blankman, J. L., Long, J. Z., Nomura, D. K., Pan, B., Kinsey, S. G., Nguyen, P. T., Ramesh, D., Booker, L., Burston, J. J., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2616 · Cited by 641 · see citing works
Self-citationStrategies for Discovering and Derisking Covalent, Irreversible Enzyme Inhibitors
Johnson, D. S., Weerapana, E., & Cravatt, B. F. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.21 · Cited by 387 · see citing works
Self-citationHuggins, J. P., Smart, T. S., Langman, S., Taylor, L., & Young, T. (2012) · Pain · doi:10.1016/j.pain.2012.04.020 · Cited by 375 · see citing works
Sharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331 · see citing works
Chemical Probes of Endocannabinoid Metabolism
Blankman, J. L., & Cravatt, B. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006387 · Cited by 327 · see citing works
Self-citationThe Endocannabinoid System: A Potential Target for the Treatment of Various Diseases
Lowe, H., Toyang, N., Steele, B., Bryant, J., & Ngwa, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179472 · Cited by 303 · see citing works
Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses
Hsu, K.-L., Tsuboi, K., Adibekian, A., Pugh, H., Masuda, K., & Cravatt, B. F. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1105 · Cited by 222 · see citing works
Self-citationKinsey, S. G., O'Neal, S. T., Long, J. Z., Cravatt, B. F., & Lichtman, A. H. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.12.002 · Cited by 170 · see citing works
Self-citationEvaluation of NHS Carbamates as a Potent and Selective Class of Endocannabinoid Hydrolase Inhibitors
Niphakis, M. J., Cognetta, A. B., Chang, J. W., Buczynski, M. W., Parsons, L. H., Byrne, F., Burston, J. J., Chapman, V., & Cravatt, B. F. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn400116z · Cited by 157 · see citing works
Self-citationInhibition of Fatty Acid Binding Proteins Elevates Brain Anandamide Levels and Produces Analgesia
Kaczocha, M., Rebecchi, M. J., Ralph, B. P., Teng, Y.-H. G., Berger, W. T., Galbavy, W., Elmes, M. W., Glaser, S. T., Wang, L., Rizzo, R. C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094200 · Cited by 142 · see citing works
“Rimonabant also blocked the antinociceptive effects of the FAAH inhibitor PF-3845, which is known to produce CB1-mediated analgesia by potentiating AEA signaling [40].”
BackgroundLee, S.-H., Ledri, M., Toth, B., Marchionni, I., Henstridge, C. M., Dudok, B., Kenesei, K., Barna, L., Szabo, S. I., Renkecz, T., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4112-14.2015 · Cited by 133 · see citing works
Ignatowska‐Jankowska, B. M., Ghosh, S., Crowe, M. S., Kinsey, S. G., Niphakis, M. J., Abdullah, R. A., Tao, Q., O' Neal, S. T., Walentiny, D. M., Wiley, J. L., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12298 · Cited by 128 · see citing works
Self-citationSubstrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation
Hermanson, D. J., Hartley, N. D., Gamble-George, J., Brown, N., Shonesy, B. C., Kingsley, P. J., Colbran, R. J., Reese, J., Marnett, L. J., & Patel, S. (2013) · Nature Neuroscience · doi:10.1038/nn.3480 · Cited by 126 · see citing works
Ghosh, S., Wise, L. E., Chen, Y., Gujjar, R., Mahadevan, A., Cravatt, B. F., & Lichtman, A. H. (2013) · Life Sciences · doi:10.1016/j.lfs.2012.06.020 · Cited by 127 · see citing works
Self-citationKinsey, S. G., Long, J. Z., Cravatt, B. F., & Lichtman, A. H. (2010) · The Journal of Pain · doi:10.1016/j.jpain.2010.04.001 · Cited by 118 · see citing works
Self-citationBooker, L., Kinsey, S. G., Abdullah, R. A., Blankman, J. L., Long, J. Z., Ezzili, C., Boger, D. L., Cravatt, B. F., & Lichtman, A. H. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01445.x · Cited by 116 · see citing works
Self-citationEnzymological studies on the biosynthesis of N-acylethanolamines
Ueda, N., Tsuboi, K., & Uyama, T. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.08.010 · Cited by 112 · see citing works
Roberts, A. M., Ward, C. C., & Nomura, D. K. (2017) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2016.08.003 · Cited by 108 · see citing works
Godlewski, G., Alapafuja, S. O., Bátkai, S., Nikas, S. P., Cinar, R., Offertáler, L., Osei-Hyiaman, D., Liu, J., Mukhopadhyay, B., Harvey-White, J., et al. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.08.013 · Cited by 95 · see citing works
Self-citationSerrano, A., Pavon, F. J., Buczynski, M. W., Schlosburg, J., Natividad, L. A., Polis, I. Y., Stouffer, D. G., Zorrilla, E. P., Roberto, M., Cravatt, B. F., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0055-3 · Cited by 83 · see citing works
Self-citationNadal, X., La Porta, C., Andreea Bura, S., & Maldonado, R. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.01.077 · Cited by 76 · see citing works
Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model
Anderson, W. B., Gould, M. J., Torres, R. D., Mitchell, V. A., & Vaughan, C. W. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.12.018 · Cited by 67 · see citing works
Enhanced functional activity of the cannabinoid type-1 receptor mediates adolescent behavior
Schneider, M., Kasanetz, F., Lynch, D. L., Friemel, C. M., Lassalle, O., Hurst, D. P., Steindel, F., Monory, K., Schäfer, C., Miederer, I., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1937-15.2015 · Cited by 56 · see citing works
Ghosh, S., Kinsey, S. G., Liu, Q.-S., Hruba, L., McMahon, L. R., Grim, T. W., Merritt, C. R., Wise, L. E., Abdullah, R. A., Selley, D. E., et al. (2015) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.222851 · Cited by 54 · see citing works
Self-citationGrim, T. W., Ghosh, S., Hsu, K.-L., Cravatt, B. F., Kinsey, S. G., & Lichtman, A. H. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.07.008 · Cited by 50 · see citing works
Self-citationToward Atomistic Modeling of Irreversible Covalent Inhibitor Binding Kinetics
Yu, H. S., Gao, C., Lupyan, D., Wu, Y., Kimura, T., Wu, C., Jacobson, L., Harder, E., Abel, R., & Wang, L. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00268 · Cited by 39 · see citing works
Nozaki, C., Markert, A., & Zimmer, A. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.04.001 · Cited by 45 · see citing works
Schlosburg, J. E., Kinsey, S. G., Ignatowska-Jankowska, B., Ramesh, D., Abdullah, R. A., Tao, Q., Booker, L., Long, J. Z., Selley, D. E., Cravatt, B. F., et al. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.212753 · Cited by 44 · see citing works
Self-citationDifferential effects of endocannabinoid catabolic inhibitors on morphine withdrawal in mice
Gamage, T. F., Ignatowska-Jankowska, B. M., Muldoon, P. P., Cravatt, B. F., Damaj, M. I., & Lichtman, A. H. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2014.11.015 · Cited by 40 · see citing works
Self-citationWills, K. L., Vemuri, K., Kalmar, A., Lee, A., Limebeer, C. L., Makriyannis, A., & Parker, L. A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3575-5 · Cited by 29 · see citing works
Synthesis and Characterization of Fatty Acid Conjugates of Niacin and Salicylic Acid
Vu, C. B., Bemis, J. E., Benson, E., Bista, P., Carney, D., Fahrner, R., Lee, D., Liu, F., Lonkar, P., Milne, J. C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01961 · Cited by 27 · see citing works
Yang, Y., Shu, Y.-Z., & Humphreys, W. G. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.5b00460 · Cited by 17 · see citing works
- Authors
- Ahn, K., Johnson, D. S., Mileni, M., Beidler, D., Long, J. Z., McKinney, M. K., Weerapana, E., Sadagopan, N., Liimatta, M., Smith, S. E., Lazerwith, S., Stiff, C., Kamtekar, S., Bhattacharya, K., Zhang, Y., Swaney, S., Van Becelaere, K., Stevens, R. C., & Cravatt, B. F.
- Affiliations
- Pfizer (United States) (US)
- Scripps Research Institute (US)
- Corresponding author
- Ahn, Kay
- Stevens, Raymond C.
- Cravatt, Benjamin F.
- ORCID
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 16
- Issue
- 4
- Pages
- 411-420
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC2692831
- OpenAlex
- W2002355116
- Cited by
- 439
- References
- 54
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 24 · 2020: 20 · 2019: 31 · 2018: 21 · 2017: 31 · 2016: 22 · 2015: 39 · 2014: 40 · 2013: 31 · 2012: 33
- FWCI
- 30.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA-017259, P01DA017259)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- fatty acid amide hydrolase, FAAH inhibitors, anandamide, endocannabinoid system, inflammatory pain, covalent inhibitors, carbamoylation, cannabinoid receptors, activity-based protein profiling, drug discovery
- MeSH terms
- Piperazine, Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Brain, Enzyme Inhibitors, Humans, Male, Pain, Piperazines, Piperidines, Structure-Activity Relationship, Urea, Rats, Sprague-Dawley, Crystallography, X-Ray, Receptors, Cannabinoid, Rats, Polyunsaturated Alkamides, Endocannabinoids
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
