220 results about "Receptor tyrosine kinase" patented technology

The present invention provides compositions and methods for treating ocular neovascularization, angiogenesis, retinal edema, diabetic retinopathy, and / or retinal ischemia in order to prevent the loss of visual acuity associated with such conditions. More specifically, the present invention provides compositions containing receptor tyrosine kinase (RTK) inhibitors having unique binding profiles and their use in treating ocular disorders.

The present invention relates to development of efficacious intravitreal pharmaceutical compositions comprising a poorly water soluble agent with anti-angiogenic and / or anti vascular leakage properties in a therapeutically effective amount and a co-solvent in a suitable amount to treat or prevent diseases due to ocular neovascularization and enhanced vascular permeability. Other aspects of the invention details the development of efficacious compositions for the treatment of the said diseases via periocular, topical and oral administration.

The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

The present invention relates to development of efficacious pharmaceutical compositions comprising an anti-angiogenic compound in a therapeutically effective amount complexed with or encapsulated in a cyclodextrin derivative.

The invention provides a method for determining the activation status of receptor tyrosine kinase (RTK) pathways in either cell samples or patient samples by measuring receptor dimerization and relative amounts of protein-protein complexes or activated effector proteins that are characteristic of an RTK pathway. The invention also provides a method of using such status information to select patients responsive to pathway-specific drugs, and more particularly, to methods for measuring ErbB receptors and receptor complexes and using such information to select patients responsive to ErbB pathway-specific drugs. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more complexes formed in RTK activation. After binding, molecular tags are released and separated from the assay mixture for analysis.

A human VEGF-related protein (VRP) has been identified and isolated that binds to, and stimulates the phosphorylation of, the receptor tyrosine kinase Flt4. The VRP is postulated to be a third member of the VEGF protein family. Also provided are antibodies that bind to VRP and neutralize a biological activity of VRP, compositions containing the VRP or antibody, methods of use, chimeric polypeptides, and a signal polypeptide for VRP.

New substituted benzimidazole compounds, compositions, and methods of inhibition of kinase activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one serine / threonine kinase or receptor tyrosine kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine / threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.

Compounds of Formula I and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula I and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hyperproliferative cell disease, particularly cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, for the treatment, management, or prevention of hyperproliferative diseases, particularly cancer. In one embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety attached to a delivery vehicle, and one or more therapeutic or prophylactic agents that treat or prevent a hyperproliferative disease, where the therapeutic or prophylactic agents are operatively associated with the delivery vehicle. In another embodiment, the method of the invention comprises administering to a subject a composition comprising a nucleic acid comprising a nucleotide sequence encoding an EphA2 or EphA4 targeting moiety and a therapeutic or prophylactic agent that treats or prevents a hyperproliferative disease. In yet another embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety and a nucleic acid comprising a nucleotide sequence encoding an agent that treats or prevents a hyperproliferative disease, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.

The present invention relates to development of efficacious pharmaceutical compositions comprising a poorly water soluble active compound in a therapeutically effective amount and a co-solvent in a suitable amount to treat or prevent diseases due to ocular neovascularization and enhanced vascular permeability. In preferred aspects the composition is in the form of a gel.

A human VEGF-related protein (VRP) has been identified and isolated that binds to, and stimulates the phosphorylation of, the receptor tyrosine kinase Flt4. The VRP is postulated to be a third member of the VEGF protein family. Also provided are antibodies that bind to VRP and neutralize a biological activity of VRP, compositions containing the VRP or antibody, methods of use, chimeric polypeptides, and a signal polypeptide for VRP.

The present invention relates to methods and compositions designed for treatment, management, or prevention of a hyperproliferative cell disease, particular cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing low molecular weight protein tyrosine kinase (“LMW-PTP”) in particular using moieties that bind an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, and inhibits or reduces LMW-PTP expression and / or activity. In one embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety attached to a delivery vehicle, and one or more agents that inhibit LMW-PTP expression and / or activity operatively associated with the delivery vehicle. In another embodiment, the method of the invention comprises administering to a subject a composition comprising a nucleic acid comprising a nucleotide sequence encoding an EphA2 or EphA4 targeting moiety and an agent that inhibits or reduces LMW-PTP expression and / or activity. In yet another embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety and a nucleic acid comprising a nucleotide sequence encoding an agent that inhibits or reduces LMW-PTP expression and / or activity, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.

Compounds of Formula (I), and stereoisomers, geometric isomers, tautomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof, are useful for inhibiting receptor tyrosine kinases and for treating hyperproliferative disorders mediated thereby. Methods of using compounds of Formula (I), and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

The present invention provides materials and methods for screening for and treating hereditary lymphedema in human subjects.

A system for analyzing tissue samples, comprising: a storage device for at least temporarily storing one or more images of one or more cells, wherein at least one of the images is indicative of one or more channels comprising a receptor tyrosine kinase (RTK); and a processing device that determines an extent to which one or more of the RTKs may have translocated from at least one subcellular region to another subcellular region of one or more of the cells; and generates a score based at least in part on the RTK translocation.

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently —O— or —NRN1−; RN1, if present, is independently —H or a substituent; RN2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH2)j-M-(CH2)k— wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently O—, —S—, —NH—, —NMe-, or —CH2—; each of RP1, RP2, RP5, and RP4 is independently —H or a substituent; and additionally RP1 and RP2 taken together may be CH═CH—CH═CH—; and additionally RP1 and RP5 taken together may be CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently CH2—, —NRN—, —C(═X)—, or —S(═O)2—; either: exactly one linker moiety is —NRN—, or: exactly two linker moieties are —NRN—; either: exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O)2—, or: exactly one linker moiety is —S(═O)2—, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NRN—; X is independently ═O or ═S; each RN is independently —H or a substituent; A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

Biaryl acetamide compounds and compositions and their methods of use are provided for modulating the activity of class III receptor tyrosine kinases and for the treatment, prevention or amelioration of one or more symptoms of disease of disorder mediated by class III receptor tyrosine kinases.

The invention provides methods of treating neoplastic disorders in a mammal through the inhibition of Mer and / or AxI receptor tyrosine kinases as well as compounds and compositions useful for inhibiting these kinases in these methods. These treatment methods may be combined with the administration of one or more chemo therapeutic agent(s) to enhance the efficacy or minimize the toxicities of the chemotherapeutic agent(s).

The invention provides novel methods for designing and administering therapeutic treatments for subjects afflicted with cancer. One aspect provides methods of identifying RTK pathways in a cancer and formulating treatment plans based on a plurality of RTK inhibitors. The invention further provides methods for evaluating candidate tyrosine kinase inhibitors for therapeutic efficacy.

The invention relates to the field of culture of tumor organoids, and in particular relates to a special medium used for in-vitro culture of esophagus cancer tumor organoid based on human esophagus cancer tissue and a culture method. The special medium comprises a receptor tyrosine kinase ligand, an Rho-associated coiled-coil protein kinase inhibitor, vitamin and hormone, an antioxidant, and an agonist for inhibiting cell differentiation pathway. According to the method, through the step-by-step culture technology adopting conditional dedifferentiation, tumor cells rapidly amplify within a short time to form the organoid. Through the step-by-step culture technology, primary cells rapidly form the organoid, meanwhile, adequate cells are formed within the effective time, so that the follow-up experiment operation can be conveniently carried out, and therefore, the culture speed and success rate of the organoid are improved.

Compounds of Formulas Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

To provide a nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane and is useful for diagnosis of leukemia; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to a region encoded by the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a nucleic acid capable of specifically binding to the nucleic acid having tandem duplication occurring in a nucleotide sequence of a juxtamembrane; a method for detection of the nucleic acid encoding a receptor protein kinase; and a kit therefor. A nucleic acid encoding a receptor protein kinase, wherein the nucleic acid has tandem duplication in a nucleotide sequence of a juxtamembrane; a polypeptide encoded by the nucleic acid; an antibody capable of specifically binding to the portion of the polypeptide; a nucleic acid capable of specifically binding to the nucleic acid; a method for detection of the nucleic acid; and a kit for detection.

This invention relates to growth regulatory proteins expressed in various disease states, especially receptor tyrosine kinases and similar growth factor receptors. Prior to the Applicants invention, it was not clear that specific antibodies could be generated that recognized peptide epitopes comprising phosphotyrosine in the context of its surrounding amino acid sequence. Applicants generated antibodies to such phosphotyrosine specific peptides, distinct from antibodies that recognize only phosphotyrosine itself. The invention includes methods for producing phosphopeptide specific antibodies by removing contaminating antibody specificities by negative and / or positive selections. Phosphospecific antibodies and their uses in immunodetection, diagnostic or therapeutic applications are also disclosed.

The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

The invention provides a culture system which contains defined components and efficiently acquires induced pluripotent stem cells (iPS cells) from somatic cells. The culture medium additive provided by the invention contains vitamin C, vitamin B12, insulin, glycogen synthase kinase-3 inhibitor, receptor tyrosine kinase and antioxidant. The culture medium additive provided by the invention can also contain a substituted serum cell growth promoter. The invention also provides a complete medium acquired by inducing pluripotent stem cells, which is prepared from one or more of basic culture medium, serum and substituted serum additive and the culture medium additive. The culture system provided by the invention does not have serum, has no animal source pollution, contains defined chemical components, efficiently acquires iPS cells, can maintain cell growth and proliferation in the process of conversion from somatic cells to iPS cells under the condition that feeder cells do not exist, simultaneously accelerates the induction course of the iPS cells obviously, and greatly improves the efficiency of inducing the somatic cells into the iPS cells.

The present invention overcomes the problems and disadvantages associated with prior art arrays by providing an array comprising a plurality of biological membrane microspots associated with a surface of a substrate that can be produced, used and stored, not in an aqueous environment, but in an environment exposed to air under ambient or controlled humidities. Preferably, the biological membrane microspots comprise a membrane bound protein. Most preferably, the membrane bound protein is a G-protein coupled receptor, an ion channel or a receptor tyrosine kinase.

The present application includes systems and methods for identifying a compound capable of interacting with a G-Protein Coupled Receptor (GPCR) or Receptor Tyrosine Kinase (RTK) including providing a device capable of measuring cell-substrate impedance operably connected to an impedance analyzer, adding test cells expressing a GPCR or a RTK to wells of the device, measuring first impedances of the wells and optionally determining first cell indices from the first impedances, adding a compound to at least one well containing test cells to form at least one compound well and adding a vehicle control to at least another well containing test cells to form at least one control well, measuring second impedances of the compound well and the control well and optionally determining second cell indices from the second impedances, determining the change in the impedance or cell index for the compound well and the one control well, comparing the change in impedance or cell index between the compound well and the control well, and identifying the compound interacts with the GPCR or RTK if the comparison demonstrates a significant difference between the change in impedance or cell index of the compound well and the control well.

The present disclosure relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same, said compounds being capable of inhibiting or antagonizing TrkA receptor tyrosine kinases. In some aspects, the disclosure provides a compound having a structural formula (I):The disclosure further concerns the use of such compounds in the treatment and / or prevention of certain types of cancers, pain, inflammation, restenosis, atherosclerosis, psoriasis, thrombosis, Alzheimer's, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.