Pharmacology articles within Nature

Featured

  • Article |

    Detailed analyses of the serotonin receptor 5-HT1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

    • Audrey L. Warren
    • , David Lankri
    •  & Daniel Wacker

  • Article
    | Open Access

    Biochemical screening and optimization identify small molecules that inhibit the formation of lipoprotein(a), and these inhibitors reduce the levels of Lp(a) in several animal models, suggesting that they could provide a therapeutic option in humans.

    • Nuria Diaz
    • , Carlos Perez
    •  & Laura F. Michael

  • Article
    | Open Access

    RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

    • Urszula N. Wasko
    • , Jingjing Jiang
    •  & Kenneth P. Olive

  • Article
    | Open Access

    A new intracellular agonist-binding pocket is identified that is common to many G protein-coupled receptors, which will have implications for the development of biased compounds that target this large group of receptors.

    • Kazuhiro Kobayashi
    • , Kouki Kawakami
    •  & Osamu Nureki

  • Article
    | Open Access

    Active-state structures of the κ-opioid receptor in complexes with the G-protein heterotrimers Gi1, GoA, Gz and Gg provide insights into the actions of hallucinogenic opioids and G-protein-coupling specificity at the κ-opioid receptor.

    • Jianming Han
    • , Jingying Zhang
    •  & Tao Che

  • Article |

    Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.

    • Christian B. Billesbølle
    • , Claire A. de March
    •  & Aashish Manglik

  • Article |

    A technique to detect the release of N-terminal fragments of Drosophila adhesion G-protein-coupled receptors (aGPCRs) provides insight into the dissociation of aGPCRs, and shows that receptor autoproteolysis enables non-cell-autonomous activity of aGPCRs in the brain.

    • Nicole Scholz
    • , Anne-Kristin Dahse
    •  & Tobias Langenhan

  • Article |

    Bitopic functionalized ligands based on fentanyl can target the sodium ion-binding site of the mu-opioid receptor and selectively modulate downstream signalling pathways, potentially leading to safer analgesics.

    • Abdelfattah Faouzi
    • , Haoqing Wang
    •  & Susruta Majumdar

  • Article
    | Open Access

    The combination of the brain-permeable mTOR inhibitor RapaLink-1 and the brain-impermeable FKBP12 ligand RapaBlock enable brain-specific inhibition of mTOR.

    • Ziyang Zhang
    • , Qiwen Fan
    •  & Kevan M. Shokat

  • Article |

    Structural determination of GAT1 using cryo-electron microscopy provides insights into the biology and pharmacology of this GABA transporter.

    • Zenia Motiwala
    • , Nanda Gowtham Aduri
    •  & Cornelius Gati

  • Article |

    Cryo-electron microscopy structures of the MRGPRX2–Gi1 trimer in complex with polycationic compound 48/80 or inflammatory peptides provide insights into the sensing of cationic allergens by MRGPRX2, potentially facilitating the design of therapies to prevent unwanted pseudoallergic reactions.

    • Fan Yang
    • , Lulu Guo
    •  & Jin-Peng Sun

  • Article |

    MIPS521, a positive allosteric modulator of the adenosine A1 receptor, has analgesic properties in a rat model of neuropathic pain through a mechanism by which MIPS521 stabilizes the complex between adenosine, receptor and G protein.

    • Christopher J. Draper-Joyce
    • , Rebecca Bhola
    •  & Arthur Christopoulos

  • Article |

    Psychedelic alkaloids served as lead structures for the development of tabernanthalog, a non-hallucinogenic and non-toxic analogue that reduces alcohol- and heroin-seeking behaviour and produces antidepressant-like effects in rodents.

    • Lindsay P. Cameron
    • , Robert J. Tombari
    •  & David E. Olson

  • Article |

    A computational screen of an ultra-large virtual library against the structure of the melatonin receptor found nanomolar ligands, and ultimately two selective MT1 inverse agonists that induced phase advancement of the mouse circadian clock when given at subjective dusk.

    • Reed M. Stein
    • , Hye Jin Kang
    •  & Margarita L. Dubocovich

  • Article |

    The structure of GLP-1R and its G protein in complex with the small molecule TT-OAD2 sheds light on how the TT-OAD2 agonist can activate the receptor and provides insights into the development of therapeutic agents for metabolic disorders.

    • Peishen Zhao
    • , Yi-Lynn Liang
    •  & Denise Wootten

  • Article |

    Cryo-electron microscopy structures are reported in which the full-length human α1β3γ2L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA, and the benzodiazepines alprazolam and diazepam.

    • Simonas Masiulis
    • , Rooma Desai
    •  & A. Radu Aricescu

  • Article |

    Chemical optimization of arylomycins results in an inhibitor of bacterial type I signal peptidase that shows activity both against multidrug-resistant clinical isolates of Gram-negative bacteria in vitro and in several in vivo infection models.

    • Peter A. Smith
    • , Michael F. T. Koehler
    •  & Christopher E. Heise

  • Article |

    A cryo-electron structure of the µ-opioid receptor in complex with the peptide agonist DAMGO and the inhibitory G protein Gi reveals structural determinants of its G protein-binding specificity.

    • Antoine Koehl
    • , Hongli Hu
    •  & Brian K. Kobilka

  • Letter |

    Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design.

    • Robert K. Y. Cheng
    • , Cédric Fiez-Vandal
    •  & Niek Dekker

  • Letter |

    The selective allosteric ABL1 inhibitor ABL001 (asciminib) represents a new inhibitory mechanism for BCR–ABL1-driven malignancies, and its efficacy and evolving mechanisms of resistance do not overlap with those of other BCR–ABL1 kinase inhibitors.

    • Andrew A. Wylie
    • , Joseph Schoepfer
    •  & William R. Sellers

  • Review Article |

    This Review discusses current knowledge of the structure, function and interactions of the metabotropic glutamate and GABAB receptors and the potential to target receptor subunits for future therapeutic intervention in neurological and mental health disorders.

    • Jean-Philippe Pin
    •  & Bernhard Bettler

  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    •  & Benjamin Haibe-Kains

  • Article |

    The metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and the (2R,6R)-HNK enantiomer lacks ketamine-related side effects but exerts rapid and sustained antidepressant actions in mice; these antidepressant effects are independent of NMDAR inhibition but require AMPAR activity.

    • Panos Zanos
    • , Ruin Moaddel
    •  & Todd D. Gould

  • Letter |

    Thalidomide and its derivative lenalidomide bind the CRL4CRBN E3 ubiquitin ligase and target protein substrates for degradation; structural and functional data determined here show that casein kinase 1α and the lymphoid transcription factor Ikaros, the efficacy targets of lenalidomide in two different blood cancers, interact with the CRBN–lenalidomide interface through a β-hairpin destruction motif.

    • Georg Petzold
    • , Eric S. Fischer
    •  & Nicolas H. Thomä

  • Letter |

    The drug daclatasvir (DCV), which inhibits the hepatitis C virus (HCV) non-structural protein 5A (NS5A), can successfully reduce viral load in patients; here, a combination of DCV and an NS5A analogue is shown to enhance DCV potency on multiple genotypes and overcome resistance in vitro and in a mouse model.

    • Jin-Hua Sun
    • , Donald R. O’Boyle II
    •  & Min Gao

  • Article |

    An automated approach designing drug ligands to multi-target profiles (with a 75% prediction success rate) is experimentally validated by the invention of novel ligands tailored to the complex and physiologically-relevant goal of identifying drugs that can specifically target profiles of multiple proteins.

    • Jérémy Besnard
    • , Gian Filippo Ruda
    •  & Andrew L. Hopkins

  • Article |

    The X-ray crystal structure of the human G-protein-coupled receptor protease-activated receptor 1 (PAR1) bound to the antagonist vorapaxar is solved, revealing an unusual method of drug binding that should facilitate the development of improved PAR1-selective antagonists.

    • Cheng Zhang
    • , Yoga Srinivasan
    •  & Brian K. Kobilka

Browse broader subjects

Browse narrower subjects

Browse Pharmacology across other nature.com journals