One for the Price of Two…Are Bivalent Ligands Targeting Cannabinoid Receptor Dimers Capable of Simultaneously Binding to both Receptors?

[1]  J. Martínez-Orgado,et al.  Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications , 2015, Neurotherapeutics.

[2]  Yasuyuki Kihara,et al.  Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1 , 2015, Cell.

[3]  D. Kendall,et al.  Minireview: From the bench, toward the clinic: therapeutic opportunities for cannabinoid receptor modulation. , 2015, Molecular endocrinology.

[4]  L. May,et al.  Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of Parkinson's disease. , 2015, Journal of medicinal chemistry.

[5]  Martin Nimczick,et al.  Design, synthesis and in vitro evaluation of novel uni- and bivalent ligands for the cannabinoid receptor type 1 with variation of spacer length and structure. , 2014, Bioorganic & medicinal chemistry letters.

[6]  Anthony Ivetac,et al.  High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875 , 2014, Nature.

[7]  B. Thomas,et al.  Toward the Development of Bivalent Ligand Probes of Cannabinoid CB1 and Orexin OX1 Receptor Heterodimers. , 2014, ACS medicinal chemistry letters.

[8]  F. Rodríguez de Fonseca,et al.  Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results , 2014, Drug design, development and therapy.

[9]  P. Portoghese,et al.  Bivalent ligands that target μ opioid (MOP) and cannabinoid1 (CB1) receptors are potent analgesics devoid of tolerance. , 2013, Journal of medicinal chemistry.

[10]  F. Bermúdez-Silva,et al.  Description of a Bivalent Cannabinoid Ligand with Hypophagic Properties , 2013, Archiv der Pharmazie.

[11]  H. Loh,et al.  Palmitoylation and membrane cholesterol stabilize μ-opioid receptor homodimerization and G protein coupling , 2012, BMC Cell Biology.

[12]  R. Stevens,et al.  Crystal Structure of a Lipid G Protein–Coupled Receptor , 2012, Science.

[13]  S. Winder,et al.  Depletion of the actin bundling protein SM22/transgelin increases actin dynamics and enhances the tumourigenic phenotypes of cells , 2012, BMC Cell Biology.

[14]  P. Gmeiner,et al.  Development of a bivalent dopamine D₂ receptor agonist. , 2011, Journal of medicinal chemistry.

[15]  P. Scammells,et al.  Design Strategies for Bivalent Ligands Targeting GPCRs , 2011, ChemMedChem.

[16]  Davide Provasi,et al.  Making Structural Sense of Dimerization Interfaces of Delta Opioid Receptor Homodimers , 2011, Biochemistry.

[17]  R. Abagyan,et al.  Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists , 2010, Science.

[18]  M. Damaj,et al.  Synthesis and biological evaluation of bivalent ligands for the cannabinoid 1 receptor. , 2010, Journal of medicinal chemistry.

[19]  Tod D Romo,et al.  A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor* , 2010, The Journal of Biological Chemistry.

[20]  G. Vauquelin,et al.  Molecular mechanisms for the persistent bronchodilatory effect of the β2‐adrenoceptor agonist salmeterol , 2009, British journal of pharmacology.

[21]  Alexandros Makriyannis,et al.  Ligand-binding architecture of human CB2 cannabinoid receptor: evidence for receptor subtype-specific binding motif and modeling GPCR activation. , 2008, Chemistry & biology.

[22]  R. Gillies,et al.  Heterobivalent ligands crosslink multiple cell-surface receptors: the human melanocortin-4 and delta-opioid receptors. , 2008, Angewandte Chemie.

[23]  Daniel Fleischer,et al.  Mutation Studies of Ser7.39 and Ser2.60 in the Human CB1 Cannabinoid Receptor: Evidence for a Serine-Induced Bend in CB1 Transmembrane Helix 7 , 2007, Molecular Pharmacology.

[24]  G. Milligan,et al.  Orexin-1 Receptor-Cannabinoid CB1 Receptor Heterodimerization Results in Both Ligand-dependent and -independent Coordinated Alterations of Receptor Localization and Function* , 2006, Journal of Biological Chemistry.

[25]  G. Wardeh,et al.  Interactions between CB1 cannabinoid and μ opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core , 2006, Neuropharmacology.

[26]  S. McAllister,et al.  Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: importance of the C-3 carboxamide oxygen/lysine3.28(192) interaction. , 2006, Journal of medicinal chemistry.

[27]  A. Makriyannis,et al.  (-)-7′-Isothiocyanato-11-hydroxy-1′,1′-dimethylheptylhexahydrocannabinol (AM841), a High-Affinity Electrophilic Ligand, Interacts Covalently with a Cysteine in Helix Six and Activates the CB1 Cannabinoid Receptor , 2005, Molecular Pharmacology.

[28]  James B. Thomas,et al.  Synthesis of long-chain amide analogs of the cannabinoid CB1 receptor antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) with unique binding selectivities and pharmacological activities. , 2005, Bioorganic & medicinal chemistry.

[29]  K. Mackie,et al.  Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk? , 2005, Molecular Pharmacology.

[30]  S. McAllister,et al.  Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches , 2004, Journal of Biological Chemistry.

[31]  Teresa Y. Phillips,et al.  Potent imidazole and triazole CB1 receptor antagonists related to SR141716. , 2004, Bioorganic & medicinal chemistry letters.

[32]  Lei Shi,et al.  The Fourth Transmembrane Segment Forms the Interface of the Dopamine D2 Receptor Homodimer* , 2003, The Journal of Biological Chemistry.

[33]  K. Mackie,et al.  Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an example. , 2002, Chemistry and physics of lipids.

[34]  Herbert H Seltzman,et al.  Synthesis and Structure−Activity Relationships of Amide and Hydrazide Analogues of the Cannabinoid CB1 Receptor Antagonist N-(Piperidinyl)- 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) , 2002 .

[35]  P. Portoghese,et al.  From models to molecules: opioid receptor dimers, bivalent ligands, and selective opioid receptor probes. , 2001, Journal of medicinal chemistry.

[36]  A. Makriyannis,et al.  Conformational studies on a diastereoisomeric pair of tricyclic nonclassical cannabinoids by NMR spectroscopy and computer molecular modeling. , 1998, Journal of medicinal chemistry.

[37]  Z. Vogel,et al.  Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. , 1995, Biochemical pharmacology.

[38]  D. Gibson,et al.  Isolation and structure of a brain constituent that binds to the cannabinoid receptor. , 1992, Science.

[39]  H. Jarrell,et al.  The orientation of (-)-delta 9-tetrahydrocannabinol in DPPC bilayers as determined from solid-state 2H-NMR. , 1989, Biochimica et biophysica acta.

[40]  D. L. Larson,et al.  Opioid agonist and antagonist bivalent ligands. The relationship between spacer length and selectivity at multiple opioid receptors. , 1986, Journal of medicinal chemistry.

[41]  V. Di Marzo.  Endocannabinoids: synthesis and degradation. , 2008, Reviews of physiology, biochemistry and pharmacology.

[42]  J. Ballesteros,et al.  Agonist alkyl tail interaction with cannabinoid CB1 receptor V6.43/I6.46 groove induces a helix 6 active conformation , 2002 .

[43]  T. Sugiura,et al.  2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. , 1995, Biochemical and biophysical research communications.

[44]  P. Portoghese,et al.  Different receptor sites mediate opioid agonism and antagonism. , 1983, Journal of medicinal chemistry.