68 results about "Chimeric molecules" patented technology

The present disclosure relates to fusion molecules and chimeric molecules which comprise two components: an Ang-2 antagonist peptide linked to a VEGF-binding moiety. Further disclosed are methods of using said chimeric molecules to treat a patient cancer, proliferative retinopathy, neovascular glaucoma, macular edema, wet age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).

The present disclosure provides peptides, chimeric molecular constructs, and compositions thereof, that can bind volatile organic compounds (VOCs) and be utilized to distinguish VOC profiles, e.g., indicative of disease, as well as related methods. A VOC-based gas sensing approach described in the present specification can be an effective screening tool, due, at least in part, to its speed, ease of use, sensitivity, specificity, and because it does not rely on binding to specific nucleic acid fragments or proteins to function.

The invention discloses a degradation agent based on indole group fusion covalent warheads and a preparation method and application thereof, and relates to the technical field of drug development, the structural formula of the degradation agent is as follows: R is a single bond or-NH-; a single bond, a, a, a, or a; and is-NH-, or; or; r1 and R2 are respectively and independently-H,-F,-Cl,-Br,-CH3,-OCH3,-NO2,-CH2-O-Ph or-CN; ph is phenyl; and a connection site is represented. According to the invention, an E3 ubiquitin ligase ligand is constructed by using an indole skeleton and acrylate, and then the E3 ubiquitin ligase ligand is connected with a BRD4 protein inhibitor JQ1 through a linker, so that a series of degradation agents based on indole group fusion covalent warheads are obtained, and targeted degradation of BRD4 protein is realized while an E3 ubiquitin ligase ligand library and a protein degradation targeted chimera molecular library are enriched.

The present disclosure relates to bifunctional compounds, which find utility as modulators of Protein Arginine N-Methyl Transferase 5 (PRMT5) in MTAP deleted / low expressing cells. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds the PRMT5-MTA complex, such that the PRMT5 protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of PRMT5 protein, as well as methods for their preparation and use. Specifically, the present invention describes compounds of Formula (I) and pharmaceutically acceptable salts, hydrates and solvates, as well as methods for their preparation and use

A chimeric molecule for enhancing mitophagy, which, at a low concentration, can effectively enhance mitophagy, repair mitochondrial damage, and thus enhance mitochondrial functions, and has been verified in various cells and in animals. The chimeric molecule has wide application values in the prevention or treatment of diseases of mitochondrial dysfunction.

To provide a chimeric molecule comprising a VWF protein fused to a heterologous moiety via a VWF linker.SOLUTION: The present invention provides an efficient VWF linker that can be cleaved in the presence of thrombin. The chimeric molecule can further comprise a polypeptide chain comprising a FVIII protein and a second heterologous moiety, and a chain comprising a VWF protein and a chain comprising a FVIII protein are associated with each other. The method also comprises a method for using a nucleotide, a vector, a host cell, and a chimeric protein.SELECTED DRAWING: None

Disclosed are substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs). The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC. The disclosed PROTACs are shown to induce degradation of c-MYC protein. The substituted heterocyclic compounds and proteolysis-targeting chimeric molecules (PROTACs) disclosed, herein may be utilized as therapeutics for treating cancer and cell proliferative disorders.

Provided herein are methods for treating or preventing, or ameliorating at least one symptom of, a neurodegenerative disease associated with TDP-43 pathology, comprising administering to a subject an effective amount of a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, optionally linked to a protein destabilization domain sequence, or a nucleic acid molecule encoding said peptide. Also provided is a peptide comprising or consisting of the amino acid sequence of SEQ ID NO:1 or a conservative variant thereof, a chimeric molecule comprising said peptide linked to a protein destabilization domain sequence, and a polynucleotide encoding said peptide or chimeric molecule.

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of IDO protein. The disclosed PROTACs typically include a first targeting moiety that binds to IDO (Miro). The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). As such, the disclosed PROTACS may be described as having a formula MIDO-L-ME3 or ME3-L-MIDO.

The present invention relates to bifunctional compounds of formula (I) (PROTAC) targeting the degradation of KAT2A and KAT2B, their manufacture, pharmaceutical compositions comprising these compounds and these compounds for use as medicaments. The compounds of the invention are useful in the treatment of diseases and medical conditions associated with KAT2A and KAT2B, including, for example, cancer, autoimmune conditions, and inflammatory conditions. # imgabs0 #

Compositions containing chimeric RNA molecules which comprise meristem targeting sequences that are fused to RNA cargo sequences that include gene editing molecules are provided. Methods of using the compositions to efficiently edit plant genomes without intervening tissue culture steps are also provided. The solutions described here relate to engineered RNA molecules useful in producing plants with altered genomes. As such, it relates to substantially purified compositions, vectors, systems, as well as genomes of plants.

The present invention relates to a chimeric molecule that enhances mitochondrial autophagy. It can effectively enhance mitochondrial autophagy at low concentrations, repair mitochondrial damage, and thus enhance mitochondrial function. The activity has been verified in a variety of cells and animals. The chimeric molecule of the present invention has a wide range of application value in preventing or treating diseases caused by mitochondrial dysfunction.

To provide tumor-associated antigens suitable for targeted antibody therapy against cancer.SOLUTION: Antigen binding molecules that specifically bind ALPPL2 and ALPP, but not ALPL and ALPI are provided. Also provided are chimeric molecules and pharmaceutical compositions comprising the antigen-binding molecules, methods of reducing the expression or activity of ALPPL2 in cancer cells, and methods of treating cancers in a subject.SELECTED DRAWING: None

In one aspect, the disclosure relates to composition and methods for proteolysis-targeting chimeric molecules (PROTACs). In some aspects, the disclosed compounds are useful for modulating LCK tyrosine kinase activity through targeted degradation. In some aspects, the disclosed compounds are orally bioavailable. In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using the same, such as T-cell acute lymphoblastic leukemia. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

A platform for therapy provides: a chimeric molecule comprising one or more auto-antigens linked by a linker to a fluorescent protein; a chimeric molecule comprising three or more components linked by linker, the components comprising two or more auto-antigens of an autoimmune disease and one or more ablative molecule and / or toxin or one or more fluorescent molecules; a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to an autoimmune disease associated HLA class or HLA class II molecule and one or more ablative molecules and / or toxins or one or more fluorescent molecules; and a chimeric molecule comprising two or more components linked by linker, the components comprising an antibody or an antigen binding fragment thereof to a disease associated T-cell receptor and one or more fluorescent molecules or one or more ablative molecule and / or toxin

The present disclosure relates to chimeric small molecules, which find utility as modifiers of target substrates according to the formula A-L1-E-B or A-L1-E-L2-B, wherein A is a kinase binding moiety; B is a target binding moiety; L1 and L2 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.

Provided herein are degrons, compositions, and chimeric molecules comprising the degrons, and methods of using the degrons and chimeric molecules.

Disclosed herein are methods and compositions comprising chimeric green fluorescent protein (GFP) molecules embedded with foreign molecules. Also disclosed are methods of treating a subject with chimeric GFP molecules embedded with foreign molecules. Further disclosed are methods of delivering a desired molecule to a cell, wherein said desired molecule is embedded within a chimeric GFP molecule.

To provide a pharmaceutical composition for treating or preventing non-proliferative diabetic retinopathy.SOLUTION: A pharmaceutical composition containing VEGF antagonist to be used in a method for bringing about at least 2 steps of improvement in a diabetic retinopathy seriousness scale (DRSS) in a patient who has non-proliferative diabetic retinopathy and needs the composition, where the patient is not suffered from diabetic macular edema including a central part. The method includes administering approximately 2 mg of VEGF antagonist being a VEGF receptor-based chimeric molecule containing: VEGFR1 component including a specific amino acid sequence; VEGFR2 component including a specific amino acid sequence; and multimerized component including a specific amino acid sequence, for 5 times of monthly dosage and subsequent once or more of secondary dosage by every 8 weeks to an eye of the patient by intravitreal injection. The VEGF antagonist is preferably aflibercept.SELECTED DRAWING: Figure 1

To provide a pharmaceutical composition for treating or preventing, or ameliorating at least one symptom of, a neurodegenerative disease associated with TDP-43 pathology, and also to provide an isolated peptide and a chimeric molecule suitable for treating and preventing the neurodegenerative disease, and a nucleic acid and a gene construct encoding the peptide and the chimeric molecule.SOLUTION: Provided is a nucleic acid comprising an expression construct encoding a peptide fragment of 14-3-3θ, a conservative variant thereof, or a sequence having at least about 75% identity to a peptide fragment of human 14-3-3θ, wherein the peptide fragment of human 14-3-3θ comprises or consists of an amino acid sequence having a specific sequence.SELECTED DRAWING: None

Described herein are methods and compositions relating to a chimeric molecule comprising: a degradation domain; and a targeting domain capable of specifically directing said degradation domain to a substrate, wherein said targeting domain is heterologous to said degradation domain.

The invention discloses a proteolysis targeting chimeric molecule capable of degrading PTBP1 in a targeting manner as well as a preparation method and application of the proteolysis targeting chimeric molecule. The invention relates to a protease targeted chimeric RNA-PTAC of a nucleic acid ligand. The protease targeted chimeric RNA-PTAC is formed by connecting an E3 ubiquitin ligase ligand pomalidomide and an RNA fragment capable of being specifically combined with PTBP1 protein through polyethylene glycol Linker. The invention relates to an RNA-PROTAC (Ribonucleic Acid-PROTAC) brain targeting delivery preparation, which is a complex obtained by coupling cell penetrating peptides TAT and RVG (Recombinant Virus Growth) with the RNA-PROTAC. According to the TR + RNA-PROTAC complex disclosed by the invention, the targets of efficiently degrading PTBP1 protein in vitro and degrading PTBP1 protein in a brain in a targeted manner in vivo are achieved through the complex, and in-vivo experiments also prove that the TR + RNA-PROTAC complex can be used for treating learning and memory disorders of mice caused by A beta and shows a good curative effect of resisting Alzheimer's disease.

This invention provides a polyfunctional chemical conjugation molecule that has been found to be useful as a modifier for target substrates. [Solution] A polyfunctional chemical conjugation molecule is provided, comprising a localization portion, a chemical linker portion, an activator portion, a first orientation adapter that interconnects the chemical linker portion to the activator portion at one end, and optionally a second orientation adapter that interconnects the chemical linker molecule to the localization portion at a different end. The molecule provides a use for post-translational modification of a polymer that is not a natural substrate of the activator portion. Diseases or disorders may be treated or prevented by this molecule.

The present disclosure relates to chimeric molecules which are fusion proteins comprising two components: an Ang-2 binding peptide linked to either a VEGF antibody or a VEGF receptor-Fc fusion protein. The Ang2 peptide, VEGF antibody, and VEGF receptor-Fc fusion proteins are each defined below with reference to percent identity to a reference sequence. The chimeric molecule is a fusion protein, dual antagonist of Ang2 and VEGF for treatment of cancers, proliferative retinopathies, neovascular glaucoma, macular edema, AMD, and rheumatoid arthritis.

To provide a composition containing a mixture of DNA molecules suitable for inhibiting targeted species, a method and use using the composition, as well as a method for producing the composition.SOLUTION: A composition for inhibiting targeted species selected from a group consisting of plants, fungi, insects, yeast, bacteria, archaea, algae, nematodes, mites, viruses, and protozoa, which have DNA sequences of different origins, wherein the mixture includes several first DNA sequences that are DNA fragments randomly generated from the chromosomal DNA sequences of the source species, and several second DNA sequences that are the second DNA sequences from host species that are different from the source species, and wherein the mixture of DNA molecules includes chimeric DNA molecules in which the DNA sequences of the source species are adjacent to non-source species' DNA sequences at at least one terminal.SELECTED DRAWING: None

The technology described herein is directed to improved chimeric molecules for, e.g, the treatment of cancer. As described herein, the inventors have developed novel chimeric aptamer-siRNA molecules (AsiCs) which demonstrate improved efficacy over existing AsiCs and which can successfully synergize in treating cancer. These AsiC's target cancer cell markers to direct therapeutic siRNA molecules specifically to cancer cells, increasing delivery efficacy and therapeutic effectiveness while reducing the potential for side effects.

The invention discloses a mitochondrial autophagy enhanced chimeric molecule based on E3 protein ubiquitin ligase ITCH and application of the mitochondrial autophagy enhanced chimeric molecule, and belongs to the field of medicinal chemistry. The structure of the chimeric molecule is I-L-O ', I represents a ligand combined with ITCH, L represents a connecting chain, and O' represents a ligand combined with mitochondrial outer membrane protein. The mitochondrial outer membrane protein comprises a translocation protein and a voltage-dependent anion channel protein. The chimeric molecule can effectively enhance mitochondrial autophagy and repair mitochondrial damage under low concentration (10-100 nanomolar concentration) so as to enhance mitochondrial functions, and verification is carried out in various cells and animal bodies, so that a blank in the field is filled.

This application relates to NKG2D-IG fusion proteins for cancer immunotherapy. The present invention provides methods and compositions for cancer immunotherapy. The methods involve using chimeric molecules (such as fusion proteins) comprising a dimeric NKG2D portion and an Fc portion, which chimeric molecules bind to one or more NKG2D ligands. In some embodiments, the molecule further comprises a drug portion (such as an IL15 / Ra portion). The methods disclosed herein are applicable to treating cancers associated with the aberrant expression of one or more NKG2D ligands.

Organic compounds for target identification, drug discovery, chemical library production, high-throughput screening, fluorophore conjugation, chemiluminescent compound conjugation, creation of proximity induced modulators (e.g., protein degraders) / chimeric molecules, or a combination thereof are described. The compounds can contain small molecule moieties for identification of their potential targets; an isocyanate, photoactivatable groups; chemical moieties for enrichment and detection of target-small molecule moiety interactions; proximity induced modulator element; fluorophores; chemiluminescent groups; or combinations thereof.

The present invention pertains to the biomedical field, and particularly relates to a chimeric molecule comprising an Ang-2 antagonist peptide and an anti-VEGF antibody, and a method for treating retinal and choroidal vascular diseases with the chimeric molecule.