36 results about "Chimeric molecules" patented technology

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

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.

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

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.

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.

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.

The invention relates to inverted chimera siRNA molecules and their use for the inhibition of expression of one or more target genes. The invention further relates to the inhibition of expression of c-Myc, or the dual inhibition of c-Myc and KRAS, using RNA interference, chemically-modified oligonucleotides, and / or chimeric siRNA multivalent combinations.

Disclosed herein is a botulinum neurotoxin (BoNT) polypeptide with a modified receptor binding domain (HC) having one or more amino acid mutations that modify the binding of the BoNT to the receptor. Specific mutations and combinations of mutations are also disclosed. Isolated modified HC, polypeptides comprising the modified HC, chimeric molecules, pharmaceutical compositions, and methods of making and using the same are also disclosed. Methods of identifying additional such modified receptor binding domains, are further disclosed.

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.

The invention relates to the technical field of biological medicine, in particular to a lysosome targeting chimeric molecule based on IGF2R-D11 structural domain targeting polypeptide and application of the lysosome targeting chimeric molecule. A novel polypeptide capable of being specifically combined with an insulin-like growth factor 2 receptor is obtained by screening through a phage display technology, the polypeptide is used as a key component and is fused with a targeting antibody through a genetic engineering method, and a bifunctional chimeric molecule capable of efficiently internalizing and mediating target protein targeting lysosome is constructed. A new technical platform is provided for the field of targeted protein degradation, and the method has important application value in the fields of tumor immunotherapy, autoimmune diseases and the like.

Methods of modulating an immune response for the treatment of cancer includes compositions which comprise chimeric molecules with an anti-CD47 binding domain and an immunomodulatory agent.

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.

The present invention relates to a 3,4-dihydrophthalazine-1(2H)-one compound represented by formula (I), pharmaceutically acceptable salts thereof, prodrugs, stable isotope derivatives, isomers, solvates, or polymorphs thereof, and pharmaceutical compositions comprising the above compound. Furthermore, the present invention also provides a method for preparing the compound represented by formula (I). The compound is used as a modulator of targeted ubiquitination, particularly for the treatment of diseases related to the CRBN protein. The compound is also used for the preparation of related proteolytic chimeric molecules (PROTACs) for CRL4 CRBN It can also be used as a ligand for E3 ubiquitin ligase. JPEG2026520709000104.jpg38149

To provide an improved chimeric molecule for treating cancer.SOLUTION: A chimeric molecule includes an EpCAM-binding aptamer domain and at least one inhibitory nucleic acid domain which inhibits expression of a gene selected from the group consisting of UPF2; PARP1; APE1; PD-L1; MCL1; PTPN2; SMG1; TREX1; CMAS; and CD47, which is an aptamer-siRNA chimera (AsiC) as one aspect, and the inhibitory nucleic acid specifically binds to a gene product of a selected gene.SELECTED DRAWING: None

Disclosed herein are CRISPR-free compositions for the production of chimeric RNA molecules via trans-splicing and methods of producing the chimeric RNA molecules, and methods of using chimeric RNA molecules produced via trans-splicing to treat and / or prevent genetic diseases or conditions.

The present disclosure provides a chimeric molecule comprising: a) a T-cell modulatory multimeric polypeptide (TMMP); and b) a nucleic acid component, where the nucleic acid component comprises a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising an antibody that binds a cancer-associated antigen. The TMMP binds to and activates a target T cell; the nucleic acid component is taken up by the target T cell such that the target T cell expresses the CAR on its surface. The present disclosure provides methods of making the chimeric molecule. The present disclosure provides treatment methods comprising administering the chimeric molecule.

The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.

Provided is a method for preparing a circular RNA or chimeric RNA by means of an RNA self-splicing ribozyme or self-splicing pair. By means of a self-splicing reaction, both ends of two independent linear RNA molecules are respectively linked to each other to form a circular RNA molecule; or one end of one linear RNA molecule is linked to one end of the other independent RNA molecule to form a chimeric RNA molecule. The chemical modification levels of the two linear RNA molecules may be independently regulated, and then the two linear RNA molecules are linked to form a circular RNA or a chimeric RNA molecule, thereby achieving chemical modification with controllable modification types and modification levels for specific regions of the circular RNA molecule or the chimeric RNA molecule. The site-specific controllable RNA modification method can significantly improve the likelihood of RNAs becoming therapeutics and reduce toxic and side effects, thereby promoting the development of RNA vaccines and drugs.

The present invention is directed to provide novel RNA molecules, chimeric NA molecules, double-stranded RNA molecules, and double-stranded chimeric NA molecules. Specifically, an embodiment of the present invention is an RNA molecule for RNA interference to target a mutant allele with a point mutation, in which (1) the molecule has a nucleotide sequence complementary to a nucleotide sequence of a coding region of the mutant allele; and (2) when counted from the base at the 5′-end in a nucleotide sequence complementary to a nucleotide sequence of the mutant allele, (2-1) a base at position 5 or 6 is mismatched to a base in the mutant allele; (2-2) a position 10 or 11 corresponds to the position of the point mutation; and (2-3) a group at the 2′-position of a pentose at positions 6-8 or positions 7 and 8 is modified with, e.g., OCH3. In this RNA molecule, one or more ribonucleotides may be replaced by, e.g., a deoxyribonucleotide. The molecule may form a double-stranded RNA with a complementary strand.

Described herein are chimeric molecules comprising (i) an anti-fibrin antibody or an antigen binding fragment thereof and (ii) one or more antithrombotic molecule(s) and uses thereof.