27 results about "Ligand binding domain" patented technology

This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and / or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.

In some aspects, the invention teaches pharmaceutical compositions that include a TGF-β ligand trap, and methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-β ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-β signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-β ligand trap to reduce right ventricular systolic pressure in a subject.

This invention provides materials and methods for regulating ligand-gated ion channel (LGIC) activity. [Solution] A modified LGIC is provided, comprising at least one LGIC subunit having a modified ligand-binding domain (LBD) and / or a modified ion-pore domain (IPD). Also provided are an exogenous LGIC ligand capable of binding to and activating the modified LGIC, as well as a method for regulating ion transport across the membrane of mammalian cells, a method for regulating cellular excitability in mammals, and a method for treating mammals with channel disorders.

The invention relates to the technical field of computational toxicology, and discloses a method for calculating combination of perfluorinated and polyfluorinated alkyl compounds and PPARalpha based on a pharmacophore model, which comprises the following steps: acquiring a PFAS initial data set, acquiring a PPARalpha ligand binding domain crystal structure, and optimizing the structure; selecting representative PFAS to carry out molecular docking, and carrying out simulated annealing optimization to obtain an optimal binding posture; then generating a pharmacophore model; the models are screened; performing rigid fitting screening by using a pharmacophore model; carrying out molecular dynamics simulation on the representative hit object, and verifying the stability; protein is extracted by culturing cells in vitro, a thermal displacement experiment is carried out, and the thermal stability effect of PFAS on PPARalpha is verified. According to the method, comprehensive virtual screening of PFAS-PPAR alpha interaction based on pharmacophores is provided, a calculation framework based on protein and compound structures is established, and the method is suitable for environmental pollutant screening and safer chemical design.

The present invention relates to a chimeric antigen receptor comprising a ligand binding domain, a transmembrane domain, a costimulatory domain and an intracellular signaling domain wherein the costimulatory domain comprises a mutated CD27 intracellular region. The invention also relates to engineered immune cells comprising such chimeric antigen receptors and their use in the treatment of diseases, such as cancer, autoimmune diseases, infections.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer in a patient who has progressed on an aromatase inhibitor. Of particular interest are ER+ cancers that do not harbor a gain of function missense mutation within the ligand binding domain (LBD) of the Estrogen Receptor 1 (ESR1) gene. The provided methods involve the administration of an effective amount of lasofoxifene, a pharmaceutically acceptable salt, prodrug or functional derivative thereof.

EphA2 targeting agents developed herein are potent peptide-mimetics with high affinity (Kds 8-20 nanomolar) for the ligand binding domain, called targefrin. Monomeric versions of targefrin act as antagonists while dimeric versions (targefrin-dimer) of the agent cause receptor internalization and degradation via a lysosomal pathway. Hence, targefrin-dimer agents are effective in reducing pro-oncogenic EphA2 levels in cancer cells when used as single agents or in combination with standards of care. Targefrin-dimers can also sensitive cancer cells that developed resistance to EGER or BRAE inhibitors, and potentially other anti-cancer agents. In addition, the dimeric agents can be conjugated with chemotherapy such as paclitaxel to deliver selectively cytotoxic agent to EphA2 expressing cancer cells. Monomeric agents can be linked to chemotherapy via a stable cleavable linker, accumulate the cytotoxic at the tumor, that then would enter the tumor. Novel composition and examples of these applications are reported.

Provided herein are mutants of the estrogen receptor alpha ligand binding domain (ER-LBD), and inducible cell death systems comprising mutants of the estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods for using the same, e.g., to induce cell death in cells.

The disclosure relates to immune cells for treatment of blood cancer comprising an activator receptor comprising an extracellular ligand binding domain specific to an activator antigen expressed by blood cancer cells and an inhibitor receptor comprising an extracellular ligand binding domain specific to an inhibitor antigen expressed by non-cancerous blood cells.

Protein complexes targeting CD47, PD-L1, and / or TIGIT are provided, as well as methods for using the same. In one embodiment, the protein complex comprises a CD47-binding domain having all or part of the SIRPα extracellular domain, a PD-L1-binding domain having all or part of the PD-1 extracellular domain, and a TIGIT ligand-binding domain having all or part of the TIGIT extracellular domain.

Herein is reported a class of chiral compounds with paradoxical effects on the androgen receptor (AR). The (R)-enantiomers behave like classical anti-androgens while the (S)-enantiomers activate AR signaling. In castration-resistant prostate cancer, the change during the course of therapy to growth in the presence of AR targeted therapeutics, a harbinger of progression to lethal disease, is commonly attributed to acquired mutations of the AR-ligand binding domain. This is the first report of an antagonist-agonist duality solely due to structural enantiomerism, without any modification to the AR binding site.

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and / or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

This document relates to materials and methods for modulating ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and / or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.

The present application relates to a kind of fusion protein for detecting anti-AMPAR1 antibody and purposes thereof.The present application specifically relates to a kind of fusion protein for detecting anti-AMPAR1 antibody, fusion protein includes extracellular amino-terminal domain, linker, extracellular ligand binding domain from N-terminal to C-terminal, the amino acid sequence of fusion protein is as shown in SEQ ID NO.1.The kit prepared from the fusion protein of the present application has the advantages of simple, accurate, high sensitivity and the like in the detection of anti-AMPAR1 antibody.

Small molecules acting through the ligand binding domain of nuclear receptor TLX (NR2E1) are disclosed, as well as the use thereof for promoting neurogenesis and treating disorders associated with nuclear receptor TLX, including neurological disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I and Formula II as described herein, and pharmaceutically acceptable salts or isomers thereof.

The present invention provides lateral flow assay devices and methods for detecting nicotinic acetylcholine receptor ligands in liquid samples. The device comprises a porous strip with multiple zones, including a sample deposition zone, a test visualization zone containing an immobilized nicotine conjugate, a control zone, and an absorbent zone. A recombinant acetylcholine receptor protein serves as a mobile agent, either pre-deposited on the strip or added to the sample. The recombinant protein comprises a ligand-binding domain of a nicotinic acetylcholine receptor conjugated to a visually-detectable reporter forming a receptor-reporter conjugate. When nicotinic acetylcholine receptor ligands are present in the sample, they competitively bind to the recombinant receptor protein, reducing binding to the immobilized nicotine conjugate and producing a visually detectable signal inversely proportional to ligand concentration. The invention provides rapid, simple, and field-deployable detection of receptor ligands in environmental samples, including cyanobacterial neurotoxins in surface waters, and biological samples for pharmacological and toxicological applications.

The present application refers to photoswitchable chemical induced dimerization systems for reversible and repetitive control of cellular activities with light. Compounds, test systems, methods and uses are disclosed how the invention can be applied in the investigation of cellular processes. A photoswitchable compound consisting of: ligand A – linker A – photoswitch moiety – linker B – ligand B or ligand (photoswitch moiety) A – linker B – ligand B, wherein ligand A, ligand (photoswitch moiety) A and ligand B are ligands capable of binding a ligand binding domain of a first and a second protein. Linker A and linker B are as specified in the specification. The photoswitch moiety is of formula (I), formula (II), the cis-isomer thereof or of formula (II) wherein R1, R2, R3, R4 and A are as defined in the specification.

Small molecules acting through the ligand binding domain of nuclear receptor TLX (NR2E1) are disclosed, as well as the use thereof for promoting neurogenesis and treating disorders associated with nuclear receptor TLX, including neurological disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula II as described herein, and pharmaceutically acceptable salts or isomers thereof.

The invention relates to a chimeric antigen receptor containing an internalizing peptide, and particularly provides a chimeric antigen receptor which comprises an extracellular ligand binding domain, a transmembrane domain and a cytoplasm domain, and the cytoplasm domain comprises the internalizing peptide. The CAR provided by the invention can significantly improve the killing effect of CAR-T cells on target cells under a low-efficiency target ratio condition, reduces the depletion of immune effector cells, can be stored for a long time in a tumor immunosuppression environment, kills tumor cells, and is low in depletion level.

The present invention provides a chimeric receptor which comprises: a ligand-binding exodomain; and an endodomain which comprises: (i) a cytokine receptor endodomain; and (ii) an intracellular T cell signalling domain.

This invention is a new strategy using a rational design for a “flexible” drug carrier composition, meaning that it provides drug release with a conformational change under specific conditions. Said carrier in its “closed” conformation, contains a drug wherein significant release of Said drug from its carrier only occurs during or after said conformational change, such as when a ligand binding domain is removed. Said carrier can then undergo a molecular, conformational change to an “open” form. The term “Allosteric Releasem” is inspired by this inventive concept.

This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and / or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channel opathy.

Provided herein are modular programmable synthetic receptors comprising a ligand binding domain, a kinase domain, and an RNase domain. Also provided herein are engineered synthetic RNAs recognized by synthetic receptors provided herein, as well as cells comprising the synthetic receptors and engineered synthetic RNAs, and methods of making and using the same.

In particular, the present invention relates to a T cell expressing a chimeric CD95 receptor comprising a polypeptide wherein the polypeptide comprises at least one CD95-derived polypeptide region having at least 60% sequence identity to a polypeptide domain, a polypeptide region or a polypeptide motif of a human CD95 wild type receptor wherein the human CD95 polypeptide region comprises a CD95 extracellular ligand binding domain; further, wherein the polypeptide comprises at least one non-CD95-derived co-stimulatory cytoplasmic polypeptide domain, region or motif of a tumor necrosis factor receptor superfamily protein, an immunoglobulin superfamily (IgSF) protein, a Toll-like receptor and / or an IL6 receptor family protein, the tumor necrosis factor receptor superfamily protein comprising CD40, CD40L, CD27, HVEM, GITR, CD30, OX40 and / or LTBR; wherein the T cell also expresses an engineered T cell receptor. The invention also relates to a vector comprising a nucleic acid encoding a CD95 receptor and an engineered T cell receptor, as well as a kit for preparing the T cell of the invention, and a pharmaceutical composition comprising said T cell. The invention also relates to a method of preparing T cells for immunotherapy and a method of treating a patient suffering from a disease comprising administering the pharmaceutical composition.

Provided herein are mutants of estrogen receptor alpha ligand binding domain (ER-LBD), and inducible cell death systems that include mutants of estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods of for use of the same, such as inducing cell death in a cell.

This document relates to materials and methods for controlling ligand gated ion channel (LGIC) activity. For example, modified LGICs including at least one LGIC subunit having a modified ligand binding domain (LBD) and / or a modified ion pore domain (IPD) are provided. Also provided are exogenous LGIC ligands that can bind to and activate the modified LGIC, as well as methods of modulating ion transport across the membrane of a cell of a mammal, methods of modulating the excitability of a cell in a mammal, and methods of treating a mammal having a channelopathy.

Provided herein are targeting constructs for sustained transgene expression of inducible cell death systems that include mutants of estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods for use of the same, such as inducing cell death in a cell.