Research Topics
Genomes and Genes | B F CravattSummaryAffiliation: The Scripps Research Institute Country: USA Publications
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Publications
The endocannabinoid anandamide is a precursor for the signaling lipid N-arachidonoyl glycine by two distinct pathwaysHeather B Bradshaw
The Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
BMC Biochem 10:14. 2009..Here using both in vitro and in vivo assays measuring metabolites with LC/MS/MS we test the hypothesis that both pathways are present in mammalian cells...- Fibroblast activation protein alpha is expressed by chondrocytes following a pro-inflammatory stimulus and is elevated in osteoarthritisJennifer M Milner
Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne, UK
Arthritis Res Ther 8:R23. 2006..Its cell surface location and expression profile suggest that it may have an important pathological role in the cartilage turnover prevalent in arthritic diseases... - Chemical strategies for the global analysis of protein functionB F Cravatt
The Skaggs Institute for Chemical Biology and the Departments of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Curr Opin Chem Biol 4:663-8. 2000..Of particular interest is a new breed of strategies that employs synthetic chemistry to enrich our understanding of protein function on a global scale... - Functional disassociation of the central and peripheral fatty acid amide signaling systemsBenjamin F Cravatt
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 101:10821-6. 2004..These data suggest that the central and peripheral FAA signaling systems regulate discrete behavioral processes and may be targeted for distinct therapeutic gain... - The biological impact of mass-spectrometry-based proteomicsBenjamin F Cravatt
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nature 450:991-1000. 2007.... - The endogenous cannabinoid system and its role in nociceptive behaviorBenjamin F Cravatt
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, California 92037, USA
J Neurobiol 61:149-60. 2004..Collectively, these investigations support a role for endocannabinoids in modulating behavioral responses to acute, inflammatory, and neuropathic pain stimuli... - Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid systemBenjamin F Cravatt
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Curr Opin Chem Biol 7:469-75. 2003.... - Activity-based protein profiling: from enzyme chemistry to proteomic chemistryBenjamin F Cravatt
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Annu Rev Biochem 77:383-414. 2008..Here, we review the basic technology of ABPP, the enzyme classes addressable by this method, and the biological discoveries attributable to its application... - Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolaseB F Cravatt
The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 98:9371-6. 2001..FAAH may therefore represent an attractive pharmaceutical target for the treatment of pain and neuropsychiatric disorders... - The enzymatic inactivation of the fatty acid amide class of signaling lipidsBenjamin F Cravatt
Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Chem Phys Lipids 121:135-48. 2002.... - Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamideD L Boger
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 97:5044-9. 2000.... - Characterization and manipulation of the acyl chain selectivity of fatty acid amide hydrolaseM P Patricelli
The Department of Cell Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Biochemistry 40:6107-15. 2001.... - Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamideD L Boger
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 95:4810-5. 1998..A select set of agents has been identified that serves both as oleamide agonists and as inhibitors of fatty acid amide hydrolase, which is responsible for the rapid inactivation of oleamide... - Comparative characterization of a wild type and transmembrane domain-deleted fatty acid amide hydrolase: identification of the transmembrane domain as a site for oligomerizationM P Patricelli
Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Biochemistry 37:15177-87. 1998..Self-association through FAAH's transmembrane domain was further demonstrated by a FAAH transmembrane domain-GST fusion protein which formed SDS-resistant dimers and large oligomeric assemblies in solution... - Molecular characterization of human and mouse fatty acid amide hydrolasesD K Giang
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 94:2238-42. 1997..The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid amides in mammalian biology... - Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolaseF Anthony Romero
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 50:1058-68. 2007..Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases, reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH... - Proteins regulating the biosynthesis and inactivation of neuromodulatory fatty acid amidesM P Patricelli
Skaggs Institute for Chemical Biology and the Department of Cell Biology, Scripps Research Institute, La Jolla, California, USA
Vitam Horm 62:95-131. 2001.... - Fatty acid amide hydrolase, the degradative enzyme for anandamide and oleamide, has selective distribution in neurons within the rat central nervous systemE A Thomas
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Neurosci Res 50:1047-52. 1997..The FAAH distribution in the CNS suggests that degradation of neuromodulatory fatty acid amides at their sites of action influences their effects on sleep, euphoria, and analgesia... - An endogenous sleep-inducing compound is a novel competitive inhibitor of fatty acid amide hydrolaseM P Patricelli
Skaggs Institute for Chemical Biology, La Jolla, California, USA
Bioorg Med Chem Lett 8:613-8. 1998..Additionally, the characterization of gamma-halo beta-keto esters as powerful FAAH inhibitors near physiological pH may aid in future studies of the enzymology and biological properties of FAAH... - Fatty acid amide hydrolase substrate specificityD L Boger
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 10:2613-6. 2000..FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural fatty acid primary amide substrates using pure recombinant rat FAAH... - Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling moleculesD L Boger
Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, USA
Curr Pharm Des 4:303-14. 1998..Oleamide has been shown to modulate serotonergic neurotransmission and inhibit intercellular gap junction communication and detailed studies of its well defined and selective structural features required for activity have been disclosed... - A functional proteomic strategy to discover inhibitors for uncharacterized hydrolasesWeiwei Li
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 129:9594-5. 2007 - A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerolJacqueline L Blankman
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Chem Biol 14:1347-56. 2007..Interestingly, MAGL, ABHD6, and ABHD12 display distinct subcellular distributions, suggesting that they may control different pools of 2-AG in the nervous system... - Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug useKyle P Chiang
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Hum Mol Genet 13:2113-9. 2004.... - Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivityDonmienne Leung
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 15:1423-8. 2005.... - Torsin A and its torsion dystonia-associated mutant forms are lumenal glycoproteins that exhibit distinct subcellular localizationsK Kustedjo
Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 275:27933-9. 2000..The potential relationship between the altered subcellular distribution of DeltaE-torsin A and the disease-inducing phenotype of the protein is discussed... - Profiling the specific reactivity of the proteome with non-directed activity-based probesG C Adam
The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
Chem Biol 8:81-95. 2001.... - A second mammalian N-myristoyltransferaseD K Giang
Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 273:6595-8. 1998.... - A second fatty acid amide hydrolase with variable distribution among placental mammalsBinqing Q Wei
The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 281:36569-78. 2006..The apparent loss of the FAAH-2 gene in some lower mammals should be taken into consideration when extrapolating genetic or pharmacological findings on the fatty acid amide signaling system across species... - Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolaseAngela B Clement
The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
J Neurosci 23:3916-23. 2003..More generally, these findings demonstrate that the disinhibitory actions of endocannabinoids observed in hippocampal slices in vitro may also occur in vivo... - Discovering potent and selective reversible inhibitors of enzymes in complex proteomesDonmienne Leung
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
Nat Biotechnol 21:687-91. 2003..In this way, promiscuous inhibitors were readily rejected in favor of equally potent compounds with 500-fold or greater selectivity for their targets... - Structural adaptations in a membrane enzyme that terminates endocannabinoid signalingMichael H Bracey
Department of Cell Biology, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 298:1793-6. 2002.... - Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolaseSalvador Huitron-Resendiz
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA
Sleep 27:857-65. 2004..To determine if, in the absence of FAAH, the hypnogenic fatty acid amides induce an increase of sleep, we characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation... - Correlation of inhibitor effects on enzyme activity and thermal stability for the integral membrane protein fatty acid amide hydrolaseIan M Slaymaker
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 18:5847-50. 2008.... - X-ray crystallographic analysis of alpha-ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolaseMauro Mileni
Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 53:230-40. 2010..The detailed analysis of their key active site interactions and their implications on the interpretation of the available structure-activity relationships are discussed providing important insights for future design... - Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case studyGabriel M Simon
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 285:11051-5. 2010.... - Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amidesB F Cravatt
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92307, USA
Nature 384:83-7. 1996..Therefore we will hereafter refer to oleamide hydrolase as fatty-acid amide hydrolase, in recognition of the plurality of fatty-acid amides that the enzyme can accept as substrates... - Profiling serine hydrolase activities in complex proteomesD Kidd
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Biochemistry 40:4005-15. 2001..Collectively, these studies demonstrate that chemical probes such as the biotinylated FPs can greatly accelerate both the functional characterization and molecular identification of active enzymes in complex proteomes... - Endocannabinoid biosynthesis proceeding through glycerophospho-N-acyl ethanolamine and a role for alpha/beta-hydrolase 4 in this pathwayGabriel M Simon
Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 281:26465-72. 2006..These results support the existence of an NAPE-PLD-independent route for NAE biosynthesis and suggest that Abh4 plays a role in this metabolic pathway by acting as a (lyso)NAPE-selective lipase... - Mechanism of carbamate inactivation of FAAH: implications for the design of covalent inhibitors and in vivo functional probes for enzymesJessica P Alexander
The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
Chem Biol 12:1179-87. 2005..The experimental strategy described herein can be used to create in vivo probes for any enzyme susceptible to covalent inhibition... - Disparate proteome reactivity profiles of carbon electrophilesEranthie Weerapana
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 4:405-7. 2008..These data specify electrophilic chemotypes with restricted and permissive reactivity profiles to guide the design of next-generation functional proteomics probes... - Biomarkers of endocannabinoid system activation in severe obesityJack C Sipe
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, United States of America
PLoS ONE 5:e8792. 2010.... - Exploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme inhibitors: Potent and selective inhibitors of fatty acid amide hydrolaseJessica K DeMartino
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 18:5842-6. 2008..90) with a slope of 3.37 (rho=3.37), that is of a magnitude that indicates that of the electron-withdrawing character of the substituent dominates its effects (a one unit change in sigma(m) provides a >1000-fold change in K(i))... - Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivoJonathan Z Long
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 106:20270-5. 2009.... - A FAAH-regulated class of N-acyl taurines that activates TRP ion channelsAlan Saghatelian
Department of Cell Biology, The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Biochemistry 45:9007-15. 2006.... - The putative endocannabinoid transport blocker LY2183240 is a potent inhibitor of FAAH and several other brain serine hydrolasesJessica P Alexander
Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 128:9699-704. 2006..More generally, the proteome-wide target promiscuity of LY2183240 designates the heterocyclic urea as a chemotype with potentially excessive protein reactivity for drug design... - Structure-guided inhibitor design for human FAAH by interspecies active site conversionMauro Mileni
The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 105:12820-4. 2008..This structure offers compelling insights to explain the species selectivity of FAAH inhibitors, which should guide future drug design programs... - Ligands in crystal structures that aid in functional characterizationAnna E Speers
The Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 66:1306-8. 2010..This introduction provides an overview and commentary on the value of liganded structures emerging from the JCSG structural genomics initiative... - Structure and function of fatty acid amide hydrolaseMichele K McKinney
Departments of Cell Biology and Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Annu Rev Biochem 74:411-32. 2005..These studies, as well as their biological and therapeutic implications, are the subject of this review... - Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesicsDale L Boger
Department of Chemistry, Cell Biology, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 48:1849-56. 2005.... - A missense mutation in human fatty acid amide hydrolase associated with problem drug useJack C Sipe
Departments of Molecular and Experimental Medicine, Chemistry, and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 99:8394-9. 2002.... - Activity-based protein profiling in vivo using a copper(i)-catalyzed azide-alkyne [3 + 2] cycloadditionAnna E Speers
The Skaggs Institute for Chemical Biology, Departments of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 125:4686-7. 2003..This click chemistry-based strategy for ABPP represents a unique and versatile method for functional proteome analysis... - Chemical strategies for activity-based proteomicsAnna E Speers
The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Chembiochem 5:41-7. 2004..These strategies for activity-based protein profiling enable both the discovery and functional analysis of enzymes associated with human disease... - Assignment of endogenous substrates to enzymes by global metabolite profilingAlan Saghatelian
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Biochemistry 43:14332-9. 2004..Thus, global metabolite profiling establishes unanticipated connections between the proteome and metabolome that enable assignment of an enzyme's unique biochemical functions in vivo... - Structural basis for a disfavored elimination reaction in catalytic antibody 1D4N A Larsen
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
J Mol Biol 314:93-102. 2001..1D4 has pushed the boundaries of antibody-mediated catalysis into the realm of disfavored reactions and, hence, represents an important milestone in the development of this technology... - Mapping enzyme active sites in complex proteomesGregory C Adam
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 126:1363-8. 2004.... - Mechanistic and structural requirements for active site labeling of phosphoglycerate mutase by spiroepoxidesMichael J Evans
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Mol Biosyst 3:495-506. 2007..More generally, our findings provide further evidence that useful pharmacological tools can emerge from screening structurally diverse libraries of protein-reactive probes... - Endocannabinoid metabolism in the absence of fatty acid amide hydrolase (FAAH): discovery of phosphorylcholine derivatives of N-acyl ethanolaminesAnke M Mulder
Department of Cell Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Biochemistry 45:11267-77. 2006..These data indicate the presence of a complete metabolic pathway for the production and degradation of PC-NAEs in the CNS that constitutes an alternative route for endocannabinoid metabolism... - Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effectsJonathan Z Long
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 5:37-44. 2009..These data indicate that 2-AG endogenously modulates several behavioral processes classically associated with the pharmacology of cannabinoids and point to overlapping and unique functions for 2-AG and anandamide in vivo... - Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid amide hydrolaseChristophe Hardouin
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 50:3359-68. 2007..Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases... - Trifunctional chemical probes for the consolidated detection and identification of enzyme activities from complex proteomesGregory C Adam
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
Mol Cell Proteomics 1:828-35. 2002.... - Profiling enzyme activities in vivo using click chemistry methodsAnna E Speers
The Skaggs Institute for Chemical Biology, Departments of Chemistry and Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Chem Biol 11:535-46. 2004.... - Binding and inactivation mechanism of a humanized fatty acid amide hydrolase by alpha-ketoheterocycle inhibitors revealed from cocrystal structuresMauro Mileni
Departments of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 131:10497-506. 2009.... - Structure-based design of a FAAH variant that discriminates between the N-acyl ethanolamine and taurine families of signaling lipidsMichele K McKinney
Department of Cell Biology, The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Biochemistry 45:9016-22. 2006..The G268D FAAH mutant may thus serve as a valuable research tool to illuminate the unique roles played by the NAE and NAT classes of signaling lipids in vivo... - Mechanism-based profiling of enzyme familiesMichael J Evans
The Skaggs Institute for Chemical Biology and Departments of Cell Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
Chem Rev 106:3279-301. 2006 - Comparison of anandamide transport in FAAH wild-type and knockout neurons: evidence for contributions by both FAAH and the CB1 receptor to anandamide uptakeSilvia Ortega-Gutierrez
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Biochemistry 43:8184-90. 2004.... - Discovery metabolite profiling--forging functional connections between the proteome and metabolomeAlan Saghatelian
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States
Life Sci 77:1759-66. 2005..These findings show that DMP can establish direct connections between the proteome and metabolome and thus offers a powerful strategy to assign physiological functions to enzymes in the post-genomic era... - Chemical strategies for functional proteomicsGregory C Adam
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
Mol Cell Proteomics 1:781-90. 2002..Additionally, we discuss the emerging field of activity-based protein profiling, which aims to synthesize and apply small molecule probes that monitor dynamics in protein function in complex proteomes... - Proteomic profiling of mechanistically distinct enzyme classes using a common chemotypeGregory C Adam
The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA
Nat Biotechnol 20:805-9. 2002..These results indicate that activity-based probes compatible with whole-proteome analysis can be developed for numerous enzyme classes and applied to identify enzymes associated with discrete pathological states... - Chemical proteomic probes for profiling cytochrome p450 activities and drug interactions in vivoAaron T Wright
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Chem Biol 14:1043-51. 2007.... - Evidence for distinct roles in catalysis for residues of the serine-serine-lysine catalytic triad of fatty acid amide hydrolaseMichele K McKinney
Department of Cell Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 278:37393-9. 2003.... - Optimization of activity-based probes for proteomic profiling of histone deacetylase complexesCleo M Salisbury
The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 130:2184-94. 2008.... - Maternal PPAR gamma protects nursing neonates by suppressing the production of inflammatory milkYihong Wan
Howard Hughes Medical Institute, Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
Genes Dev 21:1895-908. 2007..Therefore, maternal PPAR gamma is pivotal for maintaining the quality of milk and protecting the nursing newborns by suppressing the production of inflammatory lipids in the lactating mammary gland... - Class assignment of sequence-unrelated members of enzyme superfamilies by activity-based protein profilingNadim Jessani
Skaggs Institute for Chemical Biology and Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA
Angew Chem Int Ed Engl 44:2400-3. 2005 - Target discovery in small-molecule cell-based screens by in situ proteome reactivity profilingMichael J Evans
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
Nat Biotechnol 23:1303-7. 2005..More generally, the incorporation of protein-reactive compounds into chemical genomics screens offers a means to discover targets of bioactive small molecules in living systems, thereby enabling downstream mechanistic investigations... - Discovering disease-associated enzymes by proteome reactivity profilingKatherine T Barglow
The Skaggs Institute for Chemical Biology and Department of Cell Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Chem Biol 11:1523-31. 2004.... - Assignment of protein function in the postgenomic eraAlan Saghatelian
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 1:130-42. 2005..Here, we highlight a new breed of 'postgenomic' methods that aim to assign functions to proteins through the integrated application of chemical and biological techniques... - Proteomic profiling of metalloprotease activities with cocktails of active-site probesStephan A Sieber
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 2:274-81. 2006..These findings suggest that chemical proteomic methods can serve as a universal strategy to profile the activity of the metalloprotease superfamily in complex biological systems... - Characterization of monoacylglycerol lipase inhibition reveals differences in central and peripheral endocannabinoid metabolismJonathan Z Long
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd La Jolla, CA 92037, USA
Chem Biol 16:744-53. 2009..Collectively, these studies indicate that MAGL exerts tissue-dependent control over endocannabinoid and monoglyceride metabolism and designate JZL184 as a selective tool to characterize the functions of MAGL in vivo... - Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasivenessNadim Jessani
The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 99:10335-40. 2002.... - Selectivity of inhibitors of endocannabinoid biosynthesis evaluated by activity-based protein profilingHeather S Hoover
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 18:5838-41. 2008..Interestingly, a minimal overlap in target profiles was observed for THL and RHC80267, suggesting that pharmacological effects observed with both agents may be viewed as good initial evidence for DAGL-dependent events... - Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case studyRyuichiro Nakai
Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem 17:1101-8. 2009..We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes... - Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivoAron H Lichtman
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA
J Pharmacol Exp Ther 302:73-9. 2002.... - N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neuronsNeta Rimmerman
Department of Psychological and Brain Sciences, The Gill Center for Biomolecular Sciences, Indiana University, Bloomington, IN 47405, USA
Mol Pharmacol 74:213-24. 2008..Furthermore, PalGly contributed to the production of NO through calcium-sensitive nitric-oxide synthase enzymes present in F-11 cells and was inhibited by the nitric-oxide synthase inhibitor 7-nitroindazole... - Activation of the endocannabinoid system by organophosphorus nerve agentsDaniel K Nomura
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, 114 Wellman Hall, Berkeley, California 94720 3112, USA
Nat Chem Biol 4:373-8. 2008..Arachidonic acid levels are decreased by the organophosphorus agents in amounts equivalent to elevations in 2-AG, which indicates that endocannabinoid and eicosanoid signaling pathways may be coordinately regulated in the brain... - Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cellsVenkatesh L Hegde
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Rd, Columbia, SC 29209, USA
Mol Pharmacol 74:20-33. 2008..Our data demonstrate that targeting cannabinoid receptors using exogenous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalities to treat immune-mediated liver inflammation... - Evaluation of fatty acid amides in the carrageenan-induced paw edema modelLaura E Wise
Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, PO Box 980613, Richmond, VA 23298, USA
Neuropharmacology 54:181-8. 2008..While the present findings do not support a role for AEA in preventing carrageenan-induced edema, PEA administration and FAAH blockade elicited anti-edema effects of an equivalent magnitude as produced by THC, DEX, and DIC in this assay... - Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatumMauro Maccarrone
Dipartimento di Scienze Biomediche, Università degli Studi di Teramo, Piazza Aldo Moro 45, 64100 Teramo, Italy
Nat Neurosci 11:152-9. 2008..Consistently, the interaction between AEA and 2-AG was lost after pharmacological and genetic inactivation of TRPV1 channels... - Fatty acid amide hydrolase (-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze taskStephen A Varvel
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, 23298-0613, USA
J Pharmacol Exp Ther 317:251-7. 2006..More generally, FAAH may represent a novel therapeutic target that circumvents the undesirable cognitive side effects commonly associated with direct-acting cannabinoid agonists... - Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout miceBalapal S Basavarajappa
Division of Analytical Psychopharmacology, New York State Psychiatric Institute, USA
Neuropharmacology 50:834-44. 2006..Thus, the data suggest that FAAH may be indirectly related to ethanol intake and sensitivity and central endocannabinoidergic-mediated pathways may regulate ethanol consumption... - Circuitry for associative plasticity in the amygdala involves endocannabinoid signalingShahnaz C Azad
Clinical Neuropharmacology, Max Planck Institute of Psychiatry, 80804 Munich, Germany
J Neurosci 24:9953-61. 2004..This disinhibition increases the activity of common output neurons and could provide a prerequisite for extinction by formation of new memory... - Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivityAron H Lichtman
Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, P O Box 980613, Richmond, VA 23298 0613, USA
J Pharmacol Exp Ther 311:441-8. 2004.... - Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolasePal Pacher
National Institutes of Health, NIAAA, Laboratory of Physiological Studies, 5625 Fishers Lane MSC 9413, Rm 2S24, Bethesda, MD 20892 9413, USA
Am J Physiol Heart Circ Physiol 289:H533-41. 2005.... - Fatty acid amide hydrolase deficiency limits early pregnancy eventsHaibin Wang
Department of Pediatrics, Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
J Clin Invest 116:2122-31. 2006..This study uncovers what we believe to be a novel regulation of preimplantation processes, which could be clinically relevant for fertility regulation in women... - Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesiaAron H Lichtman
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA
Pain 109:319-27. 2004..In more general terms, these findings suggest that selective inhibitors of FAAH might represent a viable pharmacological approach for the clinical treatment of pain disorders... - Inhibition of fatty-acid amide hydrolase accelerates acquisition and extinction rates in a spatial memory taskStephen A Varvel
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 0613, USA
Neuropsychopharmacology 32:1032-41. 2007.... - Role of endocannabinoids in alcohol consumption and intoxication: studies of mice lacking fatty acid amide hydrolaseYuri A Blednov
Department of Neurobiology, Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712 0159, USA
Neuropsychopharmacology 32:1570-82. 2007..These data suggest that increased endocannabinoid signaling increased ethanol consumption owing to decreased acute ethanol intoxication... - Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionalityPattipati S Naidu
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 0613, USA
Psychopharmacology (Berl) 192:61-70. 2007..Manipulations of the endocannabinoid/fatty acid amide hydrolase (FAAH) signaling systems result in conflicting and paradoxical effects in rodent models of emotional reactivity... - Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolaseSandor Batkai
Section on Oxidative Stress and Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health NIAAA, 5625 Fishers Ln, MSC 9413, Bethesda, MD 20892 9413, USA
Am J Physiol Heart Circ Physiol 293:H909-18. 2007..These findings suggest that pharmacological inhibition of FAAH may represent a novel protective strategy against chronic inflammation, oxidative/nitrative stress, and apoptosis associated with cardiovascular aging and atherosclerosis...
Research Grants
- Chemical Probes for Metabolic Pathway Discovery in Human DiseaseBenjamin F Cravatt; Fiscal Year: 2010..e., annotation of uncharacterized enzymes that regulate biochemical networks in cancer), and 3) the suitability of innovative metabolomic technologies (i.e., METPR) for basic and translational applications. ..
- Enzymes That Regulate Fatty Acid Amide Function In VivoBenjamin Cravatt; Fiscal Year: 2009..These studies will elucidate the functions of key enzymes that regulate FAA signaling in vivo. These proteins may represent new targets for the treatment of pain, addiction, and other neurological disorders. ..
- Toward a potent and selective inhibitor for every mammalian serine hydrolaseBenjamin F Cravatt; Fiscal Year: 2010..The goal of this application is to develop an innovative platform to systematically discover inhibitors for uncharacterized enzymes of relevance to human health and disease. ..
- Chemical Probes for Metabolic Pathway Discovery in Human DiseaseBenjamin Cravatt; Fiscal Year: 2009..e., annotation of uncharacterized enzymes that regulate biochemical networks in cancer), and 3) the suitability of innovative metabolomic technologies (i.e., METPR) for basic and translational applications. ..
- Drug Abuse Related Polymorphism in Fatty Acid Amide HydrolaseBenjamin Cravatt; Fiscal Year: 2007..Identifying genetic contributions to drug abuse behaviors can provide powerful insights into etiology and may one day offer personalized treatment options for those at risk for these health concerns. ..
- CHEMICAL APPROACHES FOR ACTIVITY BASED PROTEOMICSBenjamin Cravatt; Fiscal Year: 2007....
- CHEMICAL APPROACHES FOR ACTIVITY BASED PROTEOMICSBenjamin Cravatt; Fiscal Year: 2003..The enzymes will in turn represent valuable targets for pharmaceutical efforts aimed at suppressing cancer metastasis. ..
- STRUCTURE/FUNCTION STUDIES OF FATTY ACID AMIDE HYDROLASEBenjamin Cravatt; Fiscal Year: 2004..abstract_text> ..
- Enzymes That Regulate Fatty Acid Amide Function In VivoBenjamin Cravatt; Fiscal Year: 2004..These studies will elucidate key enzymes that regulate FAA signaling in vivo, and these proteins may represent new targets for the treatment of pain, addiction, and other neurological disorders. ..
- Microarray Platform for Profiling Cancer ProteasesBenjamin Cravatt; Fiscal Year: 2007..These proteases may in turn represent valuable new markers and targets for the diagnosis and treatment of cancer. ..
- Massively Parallel Identification of Protein LigandsThomas J Kodadek; Fiscal Year: 2010..The synthetic compounds that we plan to identify could also serve as drug leads for a variety of therapeutically interesting targets. ..