The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.
Capsaicin ; Ligands ; Nociception

To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.
Histamine ; Ligands ; Receptors, Histamine ; Structure-Activity Relationship

Recently, along with the thorough investigation on the gene and molecular biology of peroxisome proliferators activated receptorgamma (PPARgamma), the therapeutic effects of PPARgamma ligand and its potential mechanism were gradually recognized. PPARgamma will probably become a new target of oncotherapy and is now extensively followed by researchers. This review focuses the advances of study on PPARgamma distribution in tissue, its function, its ligand in relationship with hematologic malignancies including acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, lymphoma, multiple myeloma and so on.
Hematologic Neoplasms ; metabolism ; pathology ; Humans ; Ligands ; PPAR gamma ; metabolism

G protein-coupled receptors (GPCRs) mediate signal transduction via G protein or β-arrestin. Several biased ligands and receptors that preferentially signal through either G protein- or β-arrestin-mediated pathways have been identified. These discoveries have redefined the classical GPCR signaling paradigm. Distinct ligand-receptor binding sites might be one of the main reasons for biased signal transduction. It is posited that multiple active conformations of receptors lead to distinct kinase phosphorylation patterns on C terminus of receptors. Phosphorylation patterns decide which signal pathway will be transduced. The biased signal pathway transduction has been found in more than 40 GPCRs till now. A few of them have been found involved in fine-regulation of physiological processes. However, most others still need further investigation. The biased ligands may be developed as tools for understanding the basic physiology of GPCR, and, potentially and most importantly, as fine-tuned therapeutics that maximize beneficial effects and minimize adverse or unwanted effects. These studies will provide new insights into new drug discovery.
Ligands ; Phosphorylation ; Receptors, G-Protein-Coupled ; Signal Transduction

Estrogen receptor (ER) and progesterone receptor (PR) are two important members of steroid receptors family, an evolutionarily conserved family of transcription factors. Upon binding to their ligands, ER and PR enter cell nucleus to interact with specific DNA element in the context of chromatin to initiate the transcription of diverse target genes, which largely depends on the timely recruitment of a wide range of cofactors. Moreover, the interactions between steroid hormones and their respective receptors also trigger post-translational modifications on these receptors to fine-tune their transcriptional activities. Besides the well-known phosphorylation modifications on tyrosine and serine/threonine residues, recent studies have identified several other covalent modifications, such as ubiquitylation and sumoylation. These post-translational modifications of steroid receptors affect its stability, subcellular localization, and/or cofactor recruitment; eventually influence the duration and extent of transcriptional activation. This review is to focus on the recent research progress on the transcriptional activation of nuclear ER and PR as well as their physiological functions in early pregnancy, which may help us to better understand related female reproductive diseases.
Ligands ; Phosphorylation ; Receptors, Estrogen ; Receptors, Progesterone ; Sumoylation ; Transcriptional Activation

With recent advancement in amyloid imaging, diagnostic application of this new modality has become a great interest among researchers. New ligands, such as 18F- florbetaben, florbetapir and flutemetamol, have been discovered to overcome limitations of preexisting ligand Pittsburgh compound B. We report here a case of a 37-year-old male patient whose initial complaints comprised of gradual cognitive decline, apraxia, disorientation and sleep disturbances. 18F-Florbetaben amyloid imaging of the patient showed diffuse amyloid retention with prominent striatal uptake. This finding supports the clinical utility of amyloid imaging in diagnostic process of early-onset AD. Moreover, striatal dominant uptake pattern demonstrated in this patient include some meaningful clinical implications that warrant special attention among clinicians.
Adult* ; Alzheimer Disease* ; Amyloid* ; Apraxias ; Diagnostic Imaging ; Humans ; Ligands ; Male

The emerging of network pharmacology and polypharmacology forces the scientists to recognize and explore new mechanisms of existing drugs. The drug target prediction can play a key significance on the elucidation of the molecular mechanism of drugs and drug reposition. In this paper, we systematically review the existing approaches to the prediction of biological targets of small molecule based on chemoinformatics, including ligand-based prediction, receptor-based prediction and data mining-based prediction. We also depict the strength of these methods as well as their applications, and put forward their developing direction.
Computational Biology ; Data Mining ; Drug Delivery Systems ; Drug Design ; Ligands

Scintillation proximity assay (SPA) is a unique type of radioimmunoassay and makes it possible to use radioisotopes for monitoring binding reactions continuously without separation procedure. Microbeads containing a fluorophor are covalently linked to antibody or receptor. When a radiolabeled antigen or ligand is added it binds to the beads and the emitted short range electrons, excite the fluorophor in the beads. The light emitted can be measured in a scintillation counter. 3H or 125I has been used for SPA. The sensitivities achieved with SPA are comparable to the sensitivities of other procedures. SPA is applicable to immunology, receptor binding, monitoring interactions of biomolecules and study for the kinetics of interaction between receptors and ligands.
Allergy and Immunology ; Kinetics ; Ligands ; Microspheres ; Radioimmunoassay ; Radioisotopes ; Scintillation Counting

Targeting of complex system such as human cells rather than biochemically pure molecules will be a useful approach to massively identify ligands specific for the markers associated with human disease such as cancer and simultaneously discover the specific molecular markers. In this study, we developed in vitro selection method to identify nuclease-resistant nucleic acid ligands called RNA aptamers that are specific for human cancer cells. This method is based on the combination of the cell-based selection and subtractive systematic evolution of ligands by exponential enrichment (SELEX) method. These aptamers will be useful for cancer-specific ligands for proteomic research to identify cancer-specific molecular markers as well as tumor diagnosis and therapy.
Aptamers, Nucleotide ; Diagnosis ; Humans ; Ligands* ; Proteomics ; SELEX Aptamer Technique

Estrogen receptors (ERs) are members of nuclear receptors and related to several diseases such as cancer, inflammation and osteoporosis. ERs have two forms, ERα and ERβ, which have different functions and organism distributions. Compounds selectively targeting ERβ can regulate important physiological functions and avoid the side effects caused by targeting ERα. Therefore, selective ERβ ligands have received considerable research interest in recent years. In this article, different kinds of selective ERβ ligands were summarized and their structure-activity relationships were also analyzed.
Estrogen Receptor beta ; chemistry ; Humans ; Ligands ; Structure-Activity Relationship