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References from Agonist-informed antagonist discovery: Discovery approaches, medicinal chemistry insights, and design boundaries. Local targets link to admitted publications; unresolved targets remain external evidence.
Pharmacology of antagonism of GPCR
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Approaches for differentiation and interconverting GPCR agonists and antagonists
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Structure, function and drug discovery of GPCR signaling
10.1186/s43556-023-00156-w · 2023 · External reference
Ligand control of coregulator recruitment to nuclear receptors
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Mechanisms and physiological implications of cooperative gating of clustered ion channels
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The capsaicin receptor: a heat-activated ion channel in the pain pathway
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Regulation of body temperature by the nervous system
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Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: insights from mathematical modeling and meta-analysis
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Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia
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Discovery of benzopyridone-based transient receptor potential vanilloid 1 agonists and antagonists and the structural elucidation of their activity shift
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Effect of capsaicin on thermoregulation: an update with new aspects
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Dopamine D3 receptor, cognition and cognitive dysfunctions in neuropsychiatric disorders: from the bench to the bedside
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Neuronal dopamine D3 receptors: translational implications for preclinical research and CNS disorders
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2-Phenylcyclopropylmethylamine (PCPMA) as a privileged scaffold for central nervous system drug design
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Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents
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Selective 5-hydroxytryptamine 2C receptor agonists derived from the lead compound tranylcypromine: identification of drugs with antidepressant-like action
10.1021/jm801354e · 2009 · External reference
Design and synthesis of bitopic 2-phenylcyclopropylmethylamine (PCPMA) derivatives as selective dopamine D3 receptor ligands
10.1021/acs.jmedchem.9b01835 · 2020 · External reference
Aminergic GPCR-ligand interactions: a chemical and structural map of receptor mutation data
10.1021/acs.jmedchem.8b00836 · 2019 · External reference
2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing bivalent or bitopic molecules for G-protein coupled receptors. The whole is greater than the sum of its parts
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5-HT(2C) receptor structures reveal the structural basis of GPCR polypharmacology
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A novel “activation switch” motif common to all aminergic receptors
10.1021/acs.jcim.3c00732 · 2023 · External reference
Novel regulatory mechanisms for expression of drug metabolism-related factors
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The role of pregnane X receptor (PXR) in substance metabolism
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Advances in drug resistance of osteosarcoma caused by pregnane X receptor
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Strategies for developing pregnane X receptor antagonists: implications from metabolism to cancer
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SPA70 is a potent antagonist of human pregnane X receptor
10.1038/s41467-017-00780-5 · 2017 · External reference
Building a chemical toolbox for human pregnane X receptor research: discovery of agonists, inverse agonists, and antagonists among analogs based on the unique chemical scaffold of SPA70
10.1021/acs.jmedchem.0c02201 · 2021 · External reference
Designing out PXR activity on drug discovery projects: a review of structure-based methods, empirical and computational approaches
10.1021/acs.jmedchem.0c02245 · 2021 · External reference
Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR
10.1038/s41467-024-48472-1 · 2024 · External reference
The role of peroxisome proliferator-activated receptors (PPAR) in immune responses
10.1016/j.metabol.2020.154338 · 2021 · External reference
Transcriptional and epigenomic regulation of adipogenesis
10.1128/mcb.00601-18 · 2019 · External reference
PPAR control of metabolism and cardiovascular functions
10.1038/s41569-021-00569-6 · 2021 · External reference
Fat and beyond: the diverse biology of PPARγ
10.1146/annurev.biochem.77.061307.091829 · 2008 · External reference
A novel partial agonist of peroxisome proliferator-activated receptor-gamma (PPARγ) recruits PPARγ-coactivator-1α, prevents triglyceride accumulation, and potentiates insulin signaling in vitro
10.1210/me.2005-0171 · 2006 · External reference
Design and synthesis of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility
10.1016/j.bmc.2013.02.003 · 2013 · External reference
Structural biology inspired development of a series of human peroxisome proliferator-activated receptor gamma (PPARγ) ligands: from agonist to antagonist
10.3390/ijms24043940 · 2023 · External reference
The differential interactions of peroxisome proliferator-activated receptor gamma ligands with Tyr473 is a physical basis for their unique biological activities
10.1124/mol.107.041202 · 2008 · External reference
Partial agonists activate PPARγ using a helix 12 independent mechanism
10.1016/j.str.2007.07.014 · 2007 · External reference
Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis
10.1016/j.bmc.2005.03.027 · 2005 · External reference
Peroxisome proliferator-activated receptor gamma (PPARγ) has multiple binding points that accommodate ligands in various conformations: Structurally similar PPARγ partial agonists bind to PPARγ LBD in different conformations
10.1016/j.bmcl.2015.05.025 · 2015 · External reference
Structural biology-based exploration of subtype-selective agonists for peroxisome proliferator-activated receptors
10.3390/ijms22179223 · 2021 · External reference
Molecular modeling of allosteric site of isoform-specific inhibition of the peroxisome proliferator-activated receptor PPARγ
10.3390/biom12111614 · 2022 · External reference
Arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists covalently bind to the PPARγ ligand binding domain with a unique binding mode
10.1016/j.bmcl.2022.128676 · 2022 · External reference
Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)
10.1126/science.6189183 · 1983 · External reference
HIV/AIDS
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Molecular mechanism of HIV-1 entry
10.1016/j.tim.2019.06.002 · 2019 · External reference
CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5
10.1038/384179a0 · 1996 · External reference
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Entry inhibitors in the treatment of HIV-1 infection
10.1016/j.antiviral.2009.07.022 · 2010 · External reference
HIV entry inhibitors
10.1016/s0140-6736(07)61052-6 · 2007 · External reference
The V2 domain of HIV gp120 mimics an interaction between CD4 and integrin ⍺4β7
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Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions
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Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
10.1038/31405 · 1998 · External reference
Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist
10.1021/ar4002735 · 2014 · External reference
Optimization of CD4/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis
10.1111/cbdd.12075 · 2013 · External reference
Identification of N-phenyl-N′-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4
10.1016/j.virol.2005.06.008 · 2005 · External reference
Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120
10.1016/j.str.2008.09.005 · 2008 · External reference
Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state
10.1371/journal.ppat.1000360 · 2009 · External reference
Binding mode characterization of NBD series CD4-mimetic HIV-1 entry inhibitors by X-ray structure and resistance study
10.1128/aac.03339-14 · 2014 · External reference
Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown
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Molecular characterization of a peripheral receptor for cannabinoids
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The central cannabinoid receptor type-2 (CB2) and chronic pain
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Developing the cannabinoid receptor 2 (CB2) pharmacopoeia: past, present, and future
10.1016/j.tips.2022.06.010 · 2022 · External reference
Brain cannabinoid receptor 2: expression, function and modulation
10.1038/aps.2016.149 · 2017 · External reference
Crystal structure of the human cannabinoid receptor CB2
10.1016/j.cell.2018.12.011 · 2019 · External reference
Flipping the GPCR switch: structure-based development of selective cannabinoid receptor 2 inverse agonists
10.1021/acscentsci.3c01461 · 2024 · External reference
Structural basis of selective cannabinoid CB(2) receptor activation
10.1038/s41467-023-37112-9 · 2023 · External reference
Highly selective, amine-derived cannabinoid receptor 2 probes
10.1002/chem.201904584 · 2020 · External reference
Single-position ligand modifications tune CB(2)R activity by targeting the toggle switch
10.1039/d6sc00062b · 2026 · External reference
Vitamin D and health: perspectives from mice and man
10.1359/jbmr.080420 · 2008 · External reference
Biology and mechanisms of action of the vitamin D hormone
10.1016/j.ecl.2017.07.001 · 2017 · External reference
Vitamin D in central nervous system: implications for neurological disorders
10.3390/ijms25147809 · 2024 · External reference
Vitamin D and autoimmune diseases
10.1016/j.lfs.2019.116744 · 2019 · External reference
Impact of vitamin D and vitamin D receptor activator in diabetic nephropathy
2025 · External reference
Vitamin D, disease and therapeutic opportunities
10.1038/nrd3318 · 2010 · External reference
Identification of a highly potent vitamin D receptor antagonist: (25S)-26-adamantyl-25-hydroxy-2-methylene-22,23-didehydro-19,27-dinor-20-epi-vitamin D3 (ADMI3)
10.1016/j.abb.2006.11.026 · 2007 · External reference
Synthesis and structure-activity relationships of TEI-9647 derivatives as Vitamin D3 antagonists
10.1016/j.jsbmb.2004.03.046 · 2004 · External reference
Vitamin D and its synthetic analogs
10.1021/acs.jmedchem.9b00208 · 2019 · External reference
Structural analysis of VDR complex with ZK168281 antagonist
10.1021/acs.jmedchem.0c00656 · 2020 · External reference
Crystal structures of rat vitamin D receptor bound to adamantyl vitamin D analogs: structural basis for vitamin D receptor antagonism and partial agonism
10.1021/jm8004477 · 2008 · External reference
Ligand recognition by vitamin D receptor: Total alanine scanning mutational analysis of the residues lining the ligand binding pocket of vitamin D receptor
10.2174/156802606777864881 · 2006 · External reference
Targeting adenosine A2A receptors in Parkinson's disease
10.1016/j.tins.2006.09.004 · 2006 · External reference
Therapeutic potentials of A2B adenosine receptor ligands: current status and perspectives
10.2174/1381612825666190717105834 · 2019 · External reference
A2aR antagonists: next generation checkpoint blockade for cancer immunotherapy
10.1016/j.csbj.2015.03.008 · 2015 · External reference
Inhibition of A(2A) adenosine receptor signaling in cancer cells proliferation by the novel antagonist TP455
10.3389/fphar.2017.00888 · 2017 · External reference
Adenosine A2A receptor as a drug discovery target
10.1021/jm4011669 · 2014 · External reference
The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist
10.1016/s0022-3565(25)12287-8 · 1996 · External reference
The in vitro pharmacology of ZM 241385, a potent, non-xanthine A2a selective adenosine receptor antagonist
10.1111/j.1476-5381.1995.tb15923.x · 1995 · External reference
8-(Sulfostyryl)xanthines: water-soluble A2A-selective adenosine receptor antagonists
10.1016/s0968-0896(98)00025-x · 1998 · External reference
The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist
10.1126/science.1164772 · 2008 · External reference
GPCR agonist-to-antagonist conversion: enabling the design of nucleoside functional switches for the A(2A) adenosine receptor
10.1021/acs.jmedchem.2c00462 · 2022 · External reference
Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A2A and A3 adenosine receptor ligands
10.1021/jm201229j · 2012 · External reference
Etiology of hormone receptor-defined breast cancer: a systematic review of the literature
10.1158/1055-9965.1558.13.10 · 2004 · External reference
Estrogen receptor alpha and ESR1 mutations in breast cancer
10.1007/978-3-031-11836-4_10 · 2022 · External reference
Steroidal affinity labels of the estrogen receptor. 3. Estradiol 11 beta-n-alkyl derivatives bearing a terminal electrophilic group: antiestrogenic and cytotoxic properties
10.1021/jm970019l · 1997 · External reference
Steroidal affinity labels of the estrogen receptor alpha. 4. Electrophilic 11beta-aryl derivatives of estradiol
10.1021/jm990179s · 2000 · External reference
Identification of covalent attachment site of antiestrogenic estradiol 11 beta-derivatives on human estrogen receptor alpha ligand-binding domain
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Synthesis and evaluation of 11β-(4-substituted phenyl) estradiol analogs: transition from estrogen receptor agonists to antagonists
10.1016/j.bmc.2012.04.041 · 2012 · External reference
New insights into GPCR coupling and dimerisation from cryo-EM structures
10.1016/j.sbi.2023.102574 · 2023 · External reference
AI-driven GPCR analysis, engineering, and targeting
10.1016/j.coph.2023.102427 · 2024 · External reference