1156 results about "Tyrosine kinase" patented technology

Described are conjugates formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11a, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-α (TNF-α), human tissue factor (TF), human α4β7 integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor α-chain (TAC) for diagnostic and therapeutic applications.

The present invention relates to compounds having the formula I:

which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions. The compounds of the present invention are useful in treating angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals.

The invention discloses a method for synthesizing tyrosine kinase inhibitor PCI-32765. The method comprises the following steps of: 1) carrying out a coupled reaction between a compound 10 and a compound 15 to obtain a compound 6; 2) reacting the compound 6 with a compound 16 to obtain a compound 11 in the presence of a more ideal catalyst; 3) protecting the compound 11 to obtain a compound 12; 4) carrying out selective de-protection on the compound 12 to obtain a compound 13; 5) attacking the compound 13 which has only one position which can be attacked by a compound 17 to obtain a very pure compound 14; and 6) removing protecting groups, thus obtaining the PCI-32765. By the method, tyrosine kinase which serves as a main receptor signal of B cells can be inhibited, and the tyrosine kinase inhibitor PCI-32765 is not only capable of inhabiting the generation of hemocyte with little toxicity and side effects, but also is moderate in reaction conditions, simple to operate, convenient to purify, low in cost, environment-friendly, and suitable for large scale production.

The present invention sets forth a new chemical genetic approach for engineering kinase enzymes with a cysteine gatekeeper residue as well as for developing electrophilic inhibitors thereto. The present invention also provides a Src proto-oncogenic tyrosine kinase with a cysteine gatekeeper that recapitulates wild type activity and can be irreversibly inhibited both in vitro and in cells. The present invention also provides methods and compositions for modulating kinases and for treating kinase-associated diseases.

The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.

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 present invention relates to the treatment of EGFR-mediated disease, particularly cancer, which is resistant to tyrosine kinase inhibitor therapies. Methods for treatment of cancer and reduction of tumor growth in individuals with secondary EGFR mutations, particularly tyrosine kinase domain mutations, resistant to standard therapy are provided. The invention provides methods for the treatment of tyrosine kinase inhibitor resistant cancers with anti-EGFR antibodies. Methods for treatment of recurrent lung cancer, including non-small cell lung carcinoma which is resistant to tyrosine kinase inhibitors, with the antibody anti-EGFR mAb806 are described.

A compound of the general formula (I) or pharmaceutically acceptable prodrugs, salts, hydrates, solvates, crystal forms or diastereomers thereof, wherein A represents a variety of six membered nitrogen containing heterocyclic rings, Q is a bond, halogen, C_1-4 alkyl, O, S, SO₂, CO or CS and X₁, X₂, X₃ and X₄ are optionally substituted by 9 specific substituents or one can be nitrogen. Compositions comprising a carrier and at least one compound of formula (I) are also provided. Further provided are methods of treating tyrosine kinase-associated disease states by administering a compound of formula (I) and methods of suppressing the immune system of a subject by administering a compound of formula (I).

The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.

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.

Described herein are inhibitors of FGFR, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of tyrosine kinases.

The present invention relates to novel antibodies capable of binding specifically to the human insulin-like growth factor I receptor IGF-IR and/or capable of specifically inhibiting the tyrosine kinase activity of said IGF-IR receptor, especially monoclonal antibodies of murine, chimeric and humanized origin, as well as the amino acid and nucleic acid sequences coding for these antibodies. The invention likewise comprises the use of these antibodies as a medicament for the prophylactic and/or therapeutic treatment of cancers overexpressing IGF-IR or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the overexpression of the IGF-IR receptor. The invention finally comprises products and/or compositions comprising such antibodies in combination with anti-EGFR antibodies and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.

Proteolytically stable small molecule β-turn peptidomimetic compounds have been identified as agonists or antagonists of neurotrophin receptors, such as TrkA. A compound of particular interest binds the immunoglobulin-like C2 region of the extracellular domain of TrkA, competes the binding of another TrkA ligand, affords selective trophic protection to TrkA-expressing cell lines and neuronal primary cultures, and induces the differentiation of primary neuronal cultures. The small β-turn peptidomimetic compounds of the invention can activate a tyrosine kinase neurotrophin receptor that normally binds a relatively large protein ligand. Such compounds that bind the extracellular domain of Trk receptors are useful pharmacological agents to address disorders where Trk receptors play a role, by targeting populations selectively.

Compounds of the formula

and pharmaceutically acceptable salts thereof, wherein Q¹ and R¹ are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

The present disclosure relates to the field of tyrosine kinase enzyme inhibition, in particular anaplastic lymphoma kinase (ALK) inhibition using novel small molecules. Provided are compounds capable to modulate ALK activity, compositions that comprise the compounds, and methods of using the compounds for the treatment or prevention of diseases or conditions that are characterized by ALK activity or expression.

2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, Flt3, FGFR3, Ab1, Aurora A, c-Src, IGF-1R, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

This disclosure provides tyrosine kinase protein and nucleic acid variants, particularly FGFR2 variants, which are linked to drug resistance. The disclosure further provides methods of diagnosis and theranosis, and development of new therapeutic agents using these molecules and fragments thereof, and kits for employing these methods and compositions.

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.

Disclosed are methods of treating a wound in a subject that involve administering to the subject a pharmaceutically effective amount of a composition that includes one or more human connective tissue mast cell stabilizers, wherein administration of the composition results in treatment of the wound. In particular embodiments, the wound is an ophthalmic or dermal wound, such as a corneal epithelial defect, a conjunctival wound, or dermal abrasion. Administration, for example, may be by topical application of the composition to the ocular surface or skin. Exemplary mast cell stabilizers include olopatadine, variants of olopatadine, alcaftidine, derivatives of alcaftidine, dihydropyridines, and spleen tyrosine kinase inhibitors.