321 results about "Epidermal growth factor receptor" patented technology

The present disclosure relates to at least one entity chosen from a compound of Formula (I), tautomers, stereoisomers or a mixture of stereoisomers, hydrates, and deuterated derivatives thereof, and pharmaceutically acceptable salts of any of the foregoing, and their use as epidermal growth factor receptor (EGFR) degraders for the prevention and treatment of diseases and conditions, e.g., cancer. The present disclosure also relates to pharmaceutical compositions containing such entities, and their use in treating or preventing a disease or disorder associated with EGFR.

The present invention relates to bispecific antigen binding molecules specific for both the receptor tyrosine kinase-like orphan receptor 1 (ROR1) and the epidermal growth factor receptor (EGFR), as well as related fusion proteins and conjugates. In another aspect, the invention relates to conjugated immunoglobulin-like shark variable neoantigen receptors (VNARs).

The present invention relates to a bispecific antibody comprising a first variable domain that can bind to an extracellular portion of human epidermal growth factor receptor (EGFR) and a second variable domain that can bind to an extracellular portion of human MET prooncogene receptor tyrosine kinase (cMET) for use in a method of treatment of cancer in an individual, the subject has received a previous treatment with i) a third generation EGFR tyrosine kinase inhibitor, or ii) chemotherapy and tyrosine kinase inhibitor, or iii) a cMET tyrosine kinase inhibitor.

The invention relates to the technical field of traditional Chinese medicine research, in particular to a discovery method of a cough relieving and phlegm eliminating quality marker of cough relieving granules and the quality marker. According to the application, the cough-relieving and phlegm-eliminating drug effects of the cough-relieving granules are evaluated by virtue of concentrated ammonia water cough inducing and phenol red excretion tests, plasma pharmaceutical chemistry research of the cough-relieving granules is developed by virtue of a UHPLC-Q-Exactive Plus Orbitrap HRMS technology, and 26 prototype blood-entering components of the cough-relieving granules are analyzed and identified; through network pharmacological analysis of components entering blood, 11 potential active components for relieving cough and eliminating phlegm of the cough-relieving granules are screened, relate to 40 common targets such as IL6, TLR4, STAT3 and the like, and mainly participate in signal channels such as PI3K-Akt, HIF-1, EGFR (epidermal growth factor receptor) and the like; the seven prototype blood-entering components are quantitatively analyzed by utilizing pharmacokinetics. The three compounds of azelaic acid, caffeic acid and vanillin are used as the cough relieving and phlegm eliminating quality markers of the cough relieving granules through effectiveness, transitivity and testability. The research result is of great significance in deeply defining the pharmacodynamic material basis of the cough-relieving granules, optimizing the quality standard and promoting the clinical application of the cough-relieving granules.

The invention belongs to the field of biological medicine, and relates to an anti-EGFR monoclonal antibody, a bispecific antibody thereof, a pharmaceutical composition and application. Specifically, the invention relates to an anti-EGFR antibody or an antigen binding fragment thereof. The invention also relates to an anti-EGFR (Epidermal Growth Factor Receptor) and anti-MET (Methyl The anti-EGFR monoclonal antibody and the bispecific antibody provided by the invention both have good anti-tumor activity.

The invention discloses a cetuximab variant CtxD103R of a targeted epidermal growth factor receptor drug-resistant mutant EGFRK489E (epidermal growth factor receptor). The cetuximab variant is obtained based on the rational design of wild type cetuximab. According to the present invention, the specific amino acid mutation D103R is performed on the heavy chain sequence of the wild type cetuximab, and the affinity experiment and the functional experiment are combined to research the influence of the mutated cetuximab variant CtxD103R on the drug resistance mutation EGFRK489E so as to finally prove that the cetuximab variant CtxD103R can be well combined with the EGFRK489E mutant, such that the EGFR phosphorylation can be hindered, and the EGFRK489E can be inhibited; the influence of the drug-resistant mutation K489E is weakened. The cetuximab variant CtxD103R disclosed by the invention lays a good foundation for research on resistance to drug-resistant mutation. The antibody has a wide application prospect in the field of tumor prevention and / or treatment.

The invention relates to the technical field of medicines and biology, in particular to a mouse EGFR (Epidermal Growth Factor Receptor) mutant lung adenocarcinoma cell line (EP Mus musculus) as well as preparation and application thereof. The invention provides an EP cell line ([EGFRE19delta (mutation); trp53 (deletion), EP] is derived from a lung adenocarcinoma model of a C57BL / 6 strain mouse, carries the most common EGFRE19del mutation in lung adenocarcinoma, is a first lung adenocarcinoma mouse cell line carrying EGFR mutation known in the world at present, has the in-vivo tumorigenesis ability of the C57BL / 6 strain mouse, and fills the blank of the mouse EGFR mutant cell line. The cell line provided by the invention has the background of EGFRE19del homozygous activation mutation and Trp53 homozygous deletion mutation, is sensitive to EGFR-TKI targeted therapy, can be used for in-situ tumor formation in subcutaneous and lung of an immune normal mouse C57BL / 6, and is suitable for immunotherapy and targeted therapy research of EGFR mutation lung adenocarcinoma.

The invention belongs to the technical field of medicines, and relates to a dimethyl phosphine oxide substituted aniline pyrimidine derivative targeting EGFR mutation, a preparation method and application thereof, and a medicine prepared from the dimethyl phosphine oxide substituted aniline pyrimidine derivative. The invention provides a compound as shown in a formula I. The compounds have outstanding inhibitory activity (at a nanomole level) and selectivity on EGFRT790M / C797S / L858R kinase and EGFRL858R / T790M kinase, have an obvious inhibitory effect on a non-small cell lung cancer cell line, particularly have outstanding selectivity on EGFR mutant cells H1975, and have an obvious inhibitory effect. The compound disclosed by the invention has a remarkable tumor inhibition effect in a nude mouse heterophylloma model and is relatively low in in-vivo toxicity. Therefore, the compound provided by the invention can be used as an epidermal growth factor receptor tyrosine kinase inhibitor to be applied to preparation of anti-lung cancer drugs, and has a good application prospect. And the formula I of the # imgabs0 # is shown in the specification.

The disclosure relates to macrocyclic compounds that act as inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the macrocyclic compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.

The invention discloses a polypeptide-based PROTAC condensation body as well as a preparation method and application of the polypeptide-based PROTAC condensation body. The polypeptide-based PROTAC aggregate comprises an HER2 (human epidermal growth factor receptor) targeting module, an EGFR (epidermal growth factor receptor) targeting module, a VHL E3 ligase targeting module and a self-assembly module. The polypeptide-based PROTAC condensation body can dynamically enrich E3 ligase VHL and promote efficient ubiquitination degradation of HER2, EGFR and downstream signal channel protein of HER2 and EGFR, the degradation efficiency of HER2 and EGFR protein can reach 92%, the degradation efficiency of downstream signal channel protein such as SOS2 and RAS can reach 80%, and in addition, the polypeptide-based PROTAC condensation body has the advantages that the polypeptide-based PROTAC condensation body can be used as an efficient ubiquitination condensation body; the polypeptide-based PROTAC condensation body has the characteristics of tumor targeting and long-acting retention, and dose-dependent tumor specific accumulation and retention can be realized through in-situ self-assembly.

The invention belongs to the technical field of nano-medicines and targeted therapy, and particularly relates to a targeted nano-system nano-drug delivery system based on mesoporous polydopamine as well as a preparation method and application thereof, in particular to an N2E4-MPDA-Gem nano-system based on mesoporous polydopamine (MPDA). A targeting nano system based on mesoporous polydopamine comprises mesoporous polydopamine nano particles loaded with pancreatic cancer chemotherapy drugs, targeting molecules N2E4 are combined with the surfaces of the mesoporous polydopamine nano particles, and phenylboronic acid coatings used for controlling drug release are arranged on the surfaces of the mesoporous polydopamine nano particles. The system adopts a modular design, can be compatible with various chemotherapeutic drugs such as oxaliplatin, irinotecan and the like, and can be flexibly coupled with different targeting antibodies such as EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor) and the like. A standard preparation process and good stability provide reliable guarantee for clinical transformation, and the compound shows an excellent treatment effect in a solid tumor model represented by pancreatic cancer.

The invention relates to a nitrogen-containing heteroaromatic ring compound and a preparation method and application thereof, the structure of the nitrogen-containing heteroaromatic ring compound is shown as a formula I: # imgabs0 #, and M, X, A, E, G, Z, L1, L2, Y1, Y2, R1 and R2 are defined as the specification. The nitrogen-containing heteroaromatic ring compound has a high-efficiency and high-selectivity inhibition effect on an epidermal growth factor receptor 2 (HER2), and can be used for treating related diseases caused by abnormal HER2 induction, especially treating cancer diseases.

The invention relates to the technical field of non-small cell lung cancer treatment, in particular to application of a novel epidermal growth factor receptor degradation protein hydrolysis targeting chimera DC1-206 in preparation of a medicine for treating EGFR mutant non-small cell lung cancer. The structure of the targeted chimera DC1-206 comprises an E3 ubiquitin ligase ligand, a target protein ligand EGFR-TKI and a Linker of a special structure for connecting two active ligands, a triad EGFR-PROTAC active drug molecule is finally formed, the target protein ligand of PROTAC is combined with a target protein in the body of a patient, and the targeted chimera DC1-206 can be used for preparing the targeted chimera DC1-206. According to the present invention, the E3 ubiquitin ligase ligand is combined with the substrate binding region of the E3 ubiquitin ligase in the cell, such that the target protein is pulled to the side of the E3 ubiquitin ligase through the Linker, the target protein is degraded by the UPS system, the lung cancer cell proliferation is effectively inhibited, the lung cancer cell apoptosis is promoted, and the efficient targeting tumor inhibition effect is achieved.

The present invention relates to methods of treating colorectal cancer (CRC), such as metastatic colorectal cancer (mCRC) or unresectable colorectal cancer, in a subject in need thereof, comprising administering a therapeutically effective amount of an antibody (e.g., a bispecific antibody) to the subject, wherein the antibody specifically binds epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met).

Provided herein are multispecific antibodies for redirecting T cells to cancers, that rely on binding of one antigen interacting portion of the antibody to a tumor-associated antigen or marker, such as epidermal growth factor receptor (EGFR), while a second antigen interacting portion can bind to an effector cell antigen on a T cell, such as CD3, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same.

Multi-specific binding proteins that bind to and kill human cancer cells expressing epidermal growth factor receptor 2 (HER2 or ErbB2), but does not kill non-cancerous healthy human cells expressing HER2 are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of HER2 expressing cancer. The invention also relates to multi-specific binding proteins that trigger CD8+ T cell killing of tumor cells.

Provided herein are, inter alia, antibody binding domains for cluster of differentiation 3 T cell receptor (CD3), antibody binding domains for epidermal growth factor receptor (EGFR), cleavable linker sequences, and protease-activatable bispecific fusion proteins such as protease-activatable T cell engagers, as well as uses and methods of treatment.

The invention relates to a double-response EGFR (epidermal growth factor receptor) targeted paclitaxel liposome based on heat shock protein, which adopts a pH sensitive design and is doped with heat shock protein 90 (HSP90) responsive molecule gambogic acid (GA), the surface of the liposome is modified with an EGFR antibody, and the core of the liposome is packaged with paclitaxel (PTX). According to the double-response EGFR targeted paclitaxel liposome of the heat shock protein, triple negative breast cancer cells are accurately locked through a double targeting strategy, and cell surface specific recognition is achieved through an EGFR antibody; gambogic acid GA responds to HSP90 overexpression in cells to promote drug release; the pH sensitive characteristic ensures that the medicine is quickly released in an acidic tumor microenvironment, the treatment effect is enhanced, and normal cell damage is reduced. According to the invention, the specific quick response release of the medicine is realized, the treatment accuracy and safety are improved, and the preparation method has a remarkable application prospect in the aspect of preparing the medicine for treating the triple-negative breast cancer.

Disclosed are antibodies (e.g., humanized monoclonal antibodies and antigen binding fragments) that specifically bind epidermal growth factor receptor variant III (EGFRvIII) and / or gene-amplified EGFR, as well as conjugates and chimeric antigen receptors (CARs) including such antibodies. Also provided are nucleic acid molecules encoding an antibody, conjugate, or CAR disclosed herein, and host cells expressing the nucleic acid molecules. Further disclosed are methods of using the disclosed compositions, for example, for treating or detecting a tumor, such as a tumor expressing EGFRvIII and / or gene-amplified EGFR.

The invention relates generally to variant activatable antibodies that include a masking moiety (MM), a cleavable moiety (CM), and an antibody (AB) that specifically binds to epidermal growth factor receptor (EGFR), and to methods of making and using these variant anti-EGFR activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

The invention provides a near-infrared fluorescent probe for detecting an active targeting vascular epidermal growth factor receptor as well as a preparation method and application of the near-infrared fluorescent probe, and relates to the field of organic fluorescent probe molecules. The probe provided by the invention can actively target a vascular endothelial growth factor receptor, can be quickly cleared in normal tissues, and can be detained at a tumor part for a long time, so that the effect of preparing an actual in-vivo diagnosis probe is achieved, and the probe has a good clinical application prospect and is developed and applied to clinical fluorescence-guided intraoperative navigation.

The invention provides compounds that degrade the epidermal growth factor receptor (EGFR) including mutant forms via the ubiquitination of the EGFR protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.

Provided are genetically modified NK cells expressing a chimeric antigen receptor targeting an EGFR superfamily receptor. The CAR can comprise an intracellular domain of FcεRIγ and further recombinant proteins expressed by the genetically modified NK cells are CD16, autocrine growth stimulating cytokines, and optionally one of IL-12, a TGF-beta trap, or a homing receptor. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer, comprising administering to the patient the genetically modified NK cells.

The invention belongs to the technical field of targeting peptides, and particularly relates to an EGFR targeting peptide, a fluorescent probe, a composition and application. The targeting peptide has an amino acid sequence as shown in SEQ ID NO: 1. Through verification, the targeting peptide has the capability of selective enrichment in tumor cells, and is beneficial to tumor recognition and treatment. The fluorescent probe coupled by the targeting peptide and the ICG fluorescent dye can specifically recognize and target an EGFR receptor, realizes effective aggregation and retention at a tumor part, is suitable for targeted diagnosis and treatment of tumors, can realize accurate imaging, has important clinical transformation potential, and becomes a molecular imaging probe with application prospects.

The invention relates generally to activatable antibodies that include a masking moiety (MM), a cleavable moiety (CM), and an antibody (AB) that specifically binds to epidermal growth factor receptor (EGFR), and to methods of making and using these anti-EGFR activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.

The present invention relates to bi-specific antigen binding molecules with specificity for both receptor tyrosine kinase-like orphan receptor 1 (ROR1) and epidermal growth factor receptor (EGFR) and associated fusion proteins and conjugates. In a further aspect, the present invention relates to conjugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

The invention as disclosed herein relates to bispecific antibodies that comprises a first variable domain that can bind an extracellular part of epidermal growth factor receptor (EGFR) and a second variable domain that can bind an extracellular part of MET Proto-Oncogene, Receptor Tyrosine Kinase (cMET). The antibody may comprise a common light chain. It may be a human antibody. The antibody may be a full length antibody. In some embodiments the bispecific antibody is an IgG1 format antibody having an anti-EGFR, anti-cMET stoichiometry of 1:1. In some embodiment the antibody has one variable domain that can bind EGFR and one variable domain that can bind cMET.

The invention discloses an EGFR (epidermal growth factor receptor) targeting artificial antibody based on gold nanoparticles and a preparation method of the EGFR targeting artificial antibody. The artificial antibody is composed of gold nanoparticles and unstructured polypeptide coupled with the surfaces of the gold nanoparticles. The nanogold artificial antibody is prepared by reconstructing the'dimerization arm 'conformation of the polypeptide on the surfaces of the gold nanoparticles. The artificial antibody has the capability of specifically recognizing EGFR, and is strong in binding force and good in stability. Meanwhile, the compound can be specifically combined with EGFR overexpressed cancer cells, so that proliferation of the cancer cells is inhibited, and death of the cancer cells is induced. Therefore, the artificial antibody with the function of specifically recognizing the EGFR has a wide application prospect in the fields of disease diagnosis, targeted therapy, photo-thermal therapy, drug carrying and the like.

The present disclosure provides methods of treating gastric cancer or esophageal cancer in a subject in need thereof by administering a therapeutically effective amount of a bispecific anti-epidermal growth factor receptor (EGFR) / hepatocyte growth factor receptor (c-Met) antibody.

The disclosure relates to GRAIL-1 peptide products and methods to target mutant p53 for treating p53-mutant related disease conditions such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The disclosure also relates to methods to monitor the therapeutic response of treated BE and EAC patients by detecting expression of epidermal growth factor receptor (EGER) on BE and EAC cells.