65 results about "Receptor tyrosine kinase inhibitor" 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.

A pharmaceutical combination product is disclosed that comprises a receptor tyrosine kinase inhibitor and a fatty acid synthase inhibitor, and to the use thereof in the manufacture of a medicament for use in the treatment or prophylaxis of cancer.

A method to inhibit the growth of tumors in human patients, comprising treating the human patients with an effective amount of a combination of radiation and a non-radiolabeled protein receptor tyrosine kinase inhibitor, the overexpression of which can lead to tumorigenesis.

The invention relates to administration of an anti-CTLA4 antibody, particularly human antibodies to human CTLA4, such as those having amino acid sequences of antibodies 3.1.1, 4.1.1, 4.8.1, 4.10.2, 4.13.1, 4.14.3, 6.1.1, ticilimumab (also referred to as 11.2.1 or CP-675,206), 11.6.1, 11.7.1, 12.3.1.1, 12.9.1.1, and ipilimumab (also referred to as 10D1 or MDX-010), in combination with an indolinone receptor tyrosine kinase inhibitor (RTKI), e.g., N-[2-diethylamino]ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (compound 1), N-[2-(ethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (compound 2), and 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (compound 3), for treatment of cancer. The invention relates to administering a combination of an anti-CTLA4 antibody and an indolinone RTKI such as, inter alia, compound 1. The invention relates to neoadjuvant, adjuvant, first-line, second-line, and third-line therapy of cancer, whether localized or metastasized, and at any point(s) along the disease continuum (e.g., at any stage of the cancer).

This invention provides quinazoline analogs of Formula I:where A is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to two independent R3 groups. The invention also includes methods of using compounds of Formula I as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

This invention concerns quinazoline analogs of Formula I: where an A group is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to three independent R3 groups. The invention also includes methods of using these compounds as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

The instant application provides methods and related compositions pertaining to the identification of resistance to anticancer treatment in a patient. In a particular embodiment, the invention provides biomarkers for the identification of resistance to anticancer treatment in a lung cancer patient, wherein a reduced expression of a MEDIATOR and / or SW1 / SNF complex gene in the lung cancer cells of the patient indicates that the lung cancer cells in the patient may be resistant to treatment with a receptor tyrosine kinase inhibitor, such as gefitinib and / or erlotinib. In some embodiments, the invention relates to methods and related compositions for predicting resistance to anticancer treatment by detecting the expression levels of one or more TGF-beta pathway nucleic acids and / or proteins.

Disclosed are methods and compositions for inhibiting the growth of a tumor (e.g., a malignant tumor) in a subject. In particular, combination therapies for treating a tumor in a subject by co-administering either i) an effective amount of an anti-estrogen agent or ii) an effective amount of a receptor tyrosine kinase inhibitor and an effective amount of a bispecific anti-ErbB2 / anti-ErbB3 antibody, and optionally an effective amount trastuzumab. Also disclosed is a bispecific anti-ErbB2 / anti-ErbB3 antibody for use in the therapy of a tumor in combination with either i) an anti-estrogen agent or ii) a receptor tyrosine kinase inhibitor, and optionally in use with trastuzumab.

This invention is directed to methods of preparing 4-substituted quinoline compounds as intermediates in the manufacture of receptor tyrosine kinase inhibitors and intermediate compounds used in the methods thereof, wherein the 4-substituted quinoline compound has the following general formula (I): wherein substitutions at LG″, PG, A, G, R1 and R4 are set forth in the specification.

This invention relates to detection of specific extracellular DNA in plasma or serum fractions of human or animal blood associated with neoplastic, pre-malignant or proliferative disease. Specifically, the invention relates to detection tumor-associated DNA, and to those methods of detecting and monitoring tumor-associated DNA found in the plasma or serum fraction of blood by using DNA extraction and amplification with or without enrichment for DNA. The invention allows the selection and monitoring of patients for various cancer therapies including receptor tyrosine kinase inhibitor therapies.

The invention relates to a set of isolated marker genes comprising at least one gene identified as having differential expression as between patients who are responders and non responders to an erbB receptor tyrosine kinase inhibitor; said gene set comprising one or more genes selected from at least the group consisting of the 51 genes listed herein including gene-specific oligonucleotides derived from said genes; and uses of such sets in diagnostic applications.

The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and / or an amorphous form.

The present invention relates to nanoparticles comprising a platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor, especially a PDGF receptor tyrosine kinase inhibitor having a water-solubility at 20° C. between about 2.5 g / 100 ml and 250 g / 100 ml, more specifically nanoparticles comprising an N-phenyl-2-pyrimidine-amine derivative of formula I,in which the symbols and substituents have the meanings as given herein above, in free form or in pharmaceutically acceptable salt form; to the intracellular delivery of PDGF receptor tyrosine kinase inhibitors such as Imatinib with bio-absorbable polymeric nanoparticles; the use of such nanoparticles in the manufacture of a pharmaceutical composition for the treatment of vascular smooth muscle cells growth diseases; to a method of treatment of warm-blooded animals suffering from vascular smooth muscle cells growth diseases; to a process to prepare such nanoparticles; to pharmaceutical compositions comprising such nanoparticles; and to drug delivery systems incorporating such nanoparticles for the prevention and treatment of vascular smooth muscle cells growth diseases.

Compounds of Formula I: in which A, B, R<1>, R<1a>, R<2>, R<3>, R<4>, R<5> R<6>, R<7> and R<8> have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment ofdiseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.

The present invention relates to angiogenesis inhibitors, in particular receptor tyrosine kinase inhibitors, and their use for the treatment of hyperproliferative diseases, angiogenesis and disorders depending on angiogenesis such as tumour forming cancers. It also relates to a method of inhibiting angiogenesis or treating a vascular anomaly in a mammal comprising administering to the mammal an amount of an Eph receptor inhibitor which is effective for inhibiting angiogenesis or for treating the vascular anomaly in the mammal. Further, the present invention relates to the use of compounds for the treatment of angiogenesis related disorders involving a protein kinase, preferably a tyrosine kinase, and to some specific forms of said compounds as a medicament. Compounds useful in the practice of the invention have the general formula I wherein R1, R2, R3, R4 and R5 are as defined in the specification.

The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and / or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF receptor TrkA.

The invention relates to a pyrazolo[1,5-a]miazine compound and its preparation method and medical use. The invention relates to the preparation method of the pyrazolo[1,5-a]miazine compound shown in the general formula (I) and its salt, a pharmaceutical composition containing the pyrazolo[1,5-a]miazine compound or its medicinal salt, the use of the pyrazolo[1,5-a]miazine compound or the pharmaceutical composition in the medicine field and especially as a receptor tyrosine kinase inhibitor and a c-Met inhibitor, and the use of the pyrazolo[1,5-a]miazine compound or the pharmaceutical composition in preparation of drugs for preventing and / or treating c-Met abnormality-related diseases.

The present application relates to novel quinazoline compounds as inhibitors of type I receptor tyrosine kinases, the pharmaceutical compositions comprising one or more of the compounds and salts thereof as an active ingredient, and the use of the compounds and salts thereof in the treatment of hyperproliferative diseases, such as cancer and inflammation, in mammals and especially in humans.

This invention relates to detection of specific extracellular DNA in plasma or serum fractions of human or animal blood associated with neoplastic, pre-malignant or proliferative disease. Specifically, the invention relates to detection tumor-associated DNA, and to those methods of detecting and monitoring tumor-associated DNA found in the plasma or serum fraction of blood by using DNA extraction and amplification with or without enrichment for DNA. The invention allows the selection and monitoring of patients for various cancer therapies including receptor tyrosine kinase inhibitor therapies.

The present invention relates to the administration of anti-CTLA4 antibodies, particularly human antibodies against human CTLA4, such as with antibodies 3.1.1, 4.1.1, 4.8.1, 4.10.2, 4.13.1, 4.14.3, 6.1.1, ticilimumab (also known as 11.2.1 or CP-675, 206), 11.6.1, 11.7.1, 12.3.1.1, 12.9.1.1, and antibodies to the amino acid sequences of ipilimumab (also known as 10D1 or MDX-010) , with an indolinone receptor tyrosine kinase inhibitor (RTKI), for example, N-[2-diethylamino]ethyl]-5-[(Z)-(5-fluoro-2-oxo-1, 2-dihydro-3H-indole-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carbamoyl (compound 1), N-[2-(ethylamino) Ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H -pyrrole-3-carbamoyl (compound 2), and 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indole-3-ylidene)methyl] -N-[(2S)-2-Hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carbamoyl (compound 3) combination for the treatment of cancer. The present invention relates to the administration of an anti-CTLA4 antibody in combination with an indolinone RTKI, such as, in particular, Compound 1. The present invention relates to neoadjuvant, adjuvant, first-line, second-line, and third-line treatments of cancer, whether localized or metastatic, and at any point in disease progression (eg, at any stage of the cancer).

A method for assessing the proliferation inhibiting effect of a receptor tyrosine kinase inhibitor is described. In the method, a cytoplasm is separated from a tumor cell to prepare a sample containing various receptor tyrosine kinases. The prepared sample is treated with the inhibitor. The receptor tyrosine kinases in the treated sample, and a substrate for at least two kinds of receptor tyrosine kinases are contacted. The phosphorylated substrate is detected, and the activity value of the receptor tyrosine kinases is measured based on the detection result. The proliferation inhibiting effect is assessed based on the resulting activity value.

An in vivo method for the identification and / or validation of receptor tyrosine kinase inhibitors is described. Said method is characterised by the following steps: providing host cells comprising a nucleic acid construct encoding a peptide which comprises a tyrosine kinase domain of a receptor tyrosine kinase wherein said peptide lacks a transmembrane domain or a functional fragment thereof and said tyrosine kinase activity in the cytoplasma leads to proliferation arrest, contacting said host cells with a candidate compound and identification of inhibitors of said tyrosine kinase activity by cultivation of said host cells under suitable conditions such that the modulation of the tyrosine kinase activity by the candidate compound leads to cell growth.

The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and / or an amorphous form.

The invention belongs to the field of biopharmacy and relates to 2-(quinazoline-4-amino)-5-thiazole carboxamide derivatives and a biological medicine use thereof. Based on a crystal structure of a compound of high-quality Src receptor tyrosine kinase and a Src receptor tyrosine kinase inhibitor saracatinib, a Src active pocket is defined, and a searching process is carried out on a known chemical storage by high-speed virtual screening software DOCK and an accurate scoring function so that the 2-(quinazoline-4-amino)-5-thiazole carboxamide small-molecular compounds having high inhibition activity to Src are obtained. A biological activity test proves that the 2-(quinazoline-4-amino)-5-thiazole carboxamide small-molecular compounds have strong inhibition activity to Src receptor tyrosine kinase, can be used for preparing antitumor drugs especially such as a drug for resisting Src kinase signal transduction system adjustment disorder-caused tumors, can be used as drug lead compounds for synthesis of a novel Src kinases inhibitor and especially can be used for treating Src-related tumor diseases.

Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.