90 results about "ALK inhibitor" patented technology

A compound represented by the general Formula (I) below, or a salt or solvate thereof, which is useful as an ALK inhibitor, and is useful for prophylaxis or treatment of a disease accompanied by abnormality in ALK, for example, cancer, cancer metastasis, depression or cognitive function disorder:(meanings of the symbols that are included in the formula are as given in the specification).

Compositions and methods for the diagnosis and treatment of a cancer that is resistant to at least one anaplastic lymphoma kinase (ALK) kinase inhibitor are provided herein. The present invention is based on the discovery of mutations within ALK that confer resistance to at least one ALK kinase inhibitor. Polynucleotides and polypeptides having at least one ALK inhibitor resistance mutation are provided and find use in methods and compositions useful in the diagnosis, prognosis, and / or treatment of diseases associated with aberrant ALK activity, more particularly, those that are resistant to at least one ALK kinase inhibitors. Methods and compositions are also provided for the identification of agents that can inhibit the kinase activity and / or reduce the expression level of the ALK resistance mutants.

The invention discloses a spiro aryl phosphorus oxide or sulfide as ALK inhibitor, and in particular discloses a compound shown in a formula (I) as an ALK inhibitor or a pharmaceutically acceptable salt thereof.

The present invention relates to macrocyclic compounds of Formula I:or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK / ALK inhibitors useful in the treatment of JAK / ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

The invention discloses inhibitors with ALK and EGFR dual activity, and a preparation method and an application thereof, and relates to N-(3-((4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidine-2-yl)amino)phenyl)acryloylamide analogs represented by formula (I), and stereoisomers or pharmaceutically acceptable salts thereof. The series of compounds have epidermal growth factor receptor (EGFR) L858R EGFR mutant, T790MEGFR mutant and exon 19 deleted active mutant inhibition activity, and also have ALK inhibition activity, so the series of compounds can be used to treat EGFR mutant and ALK activity individually or partially mediated diseases, can be widely applied to medicines for preventing and treating cancers and especially non-small cell lung cancers, and is hopeful to be developed into new generation EGFR or / and ALK inhibitors.

The invention provides a pyrimidine derivative used as an ALK inhibitor. The pyrimidine derivative is a compound as shown in a formula I which is described in the specification or a pharmaceutical salt, hydrate, solvate, metabolite or prodrug thereof. R1, R2, R3 and R4 in the formula are as defined in the specification. The compound and a pharmaceutical composition thereof can be used as the ALK inhibitor and for preparation of an antineoplastic therapeutic capable of inhibiting ALK.

The invention relates to ALK-targeted PROTAC and application thereof, and belongs to the technical field of anti-tumor drugs. The invention aims to provide an ALK-targeted PROTAC molecule. The PROTACmolecule has the structural formula which is shown in a formula I. A ligand pomalidomide of CRBN and a derivative of pomalidomide are adopted as a ligand of an E3 ligase, and coupling of an ALK inhibitor LDK378 with the E3 ligase is achieved through linkers of different types and different chain lengths so as to prepare the ALK-targeted PROTAC molecule successfully; through the ALK-targeted PROTACmolecule, target proteins can be targeted effectively, the content of ALK in cells is reduced, and meanwhile, the ALK-targeted PROTAC is characteristics of good anti-tumor activity in vitro and in vivo, low toxicity to normal cells and high efficiency and low toxicity.

The invention provides methods for using compounds of formula (I) for treating an EML4-ALK+ mediated condition such as EML4-ALK+ non-small cell lung cancer, and optionally resistant to crizotinib; wherein R1, R2, R3, R4, R5 and R6 are as defined above.

The invention provides a kinase inhibitor and application thereof. The compound is a compound shown in a formula I or pharmaceutical salt, a hydrate, a solvate, a metabolite or a prodrug of the compound shown in the formula I, wherein R1 and R2 are defined in the description. The compound and a pharmaceutical composition can be used for preparing an ALK inhibitor and drugs for treating or preventing cancers and inhibiting the proliferative effect of cancer cells. The formula I is shown in the description.

The invention relates to the fields of cytobiology and cell culture, and particularly relates to a breast cancer organoid culture kit. A method for realizing the kit comprises the following steps: (1)preparing, sub-packaging and using a breast cancer organoid culture medium A; (2) preparing, sub-packaging and using a breast cancer organoid culture medium B; and (3) preparing, sub-packaging and using a sample preserving fluid. The breast cancer organoid culture medium A is a DMEM / F12 culture medium containing 100 U / ml of penicillin, 0.1 mg / ml of streptomycin, 1% of HEPES and 1% of Gluta Max 100 X; the organoid culture medium B is a DMEM / F12 culture medium containing EGF, an FGF growth factor, an ALK inhibitor A83-01, Noggin, an HEPES buffer solution, Y27632 and one or more of a Wnt signalpath related secretory protein family R-Spondin 1-4; and the sample preserving fluid is a DMEM / F12 culture medium containing 100 U / ml of penicillin, 0.1 mg / ml of streptomycin and 1% of L-glutamine. The three components form the breast cancer organoid culture kit.

A pharmaceutical combination comprising (a) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, and (b) at least one HDMA-2 / p53 receptor inhibitor or a pharmaceutically acceptable salt, or at least one BRaf inhibitor or a pharmaceutically acceptable salt, and optionally a pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of cancer; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

The invention discloses a preparation method of an ALK inhibitor crizotinib and analogue or salt thereof. The method comprise the following steps: 1, 1-(4'-N-Boc)-1'-piperidine-3(3''-fluoro-2''-nitro)-5''-pyridylpyrazole is prepared; 2, 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-N-Boc-piperidinyl)-1H-pyrazol-4-yl]-2-nitropyridine is prepared; 3, N-Boc crizotinib is prepared; and 4, crizotinib and analogue or salt thereof is prepared. The method has the following advantages: the synthesis steps are reduced to 4 chemical reaction steps; a total yield is improved to approximately 35%, while the yield of an existing method is only approximately 10%; phenethyl alcohol with (R)- configuration, such as (R)-2,6-dichloro-3-fluorophenylethanol, is directly used as a raw material, such that the raw material can be fully utilized. The method provided by the invention is suitable for industrialized productions.

The invention discloses application of a pyridylamine compound in preparation of a pharmaceutical composition used for treating a lung cancer and suitable for oral administration and aims to overcome problems in effective application of an ALK inhibitor in treatment. The pharmaceutical composition provided by the invention contains the pyridylamine compound having a structure as represented by formula I, an active component and an optional pharmaceutically acceptable carrier, adjuvant or excipient, wherein the active component is one or a mixture of two selected from the group consisting of pharmaceutically acceptable salts of the pyridylamine compound, and the effective treatment dose of the pharmaceutical composition is 340 to 680 mg / d in terms of the amount of the pyridylamine compound having the structure as represented by formula I. The pyridylamine compound can be effectively applied in treatment of EML4-ALK-positive non-small cell lung cancers and has a substantial treatment effect and low toxic response.

The present invention relates to macrocyclic compounds of Formula I:or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK / ALK inhibitors useful in the treatment of JAK / ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

The invention discloses a neural stem cell induction differentiation medium and a neural stem cell induction differentiation method. Specifically, the neural stem cell induction differentiation mediumcomprises a basic medium and additives. The basic medium is a DMEM / F12 medium. The additives include 1-5mM glutamine, a 2-8microM GSK-3 inhibitor, a 2-10microM BMP inhibitor, a 2-10microM ALK inhibitor, 0.5%-2% of a cell culture additive and 0.5%-2% of a double-antibody. The neural stem cell induction differentiation medium provided by the invention has the characteristics of clear and simple components, high differentiation efficiency, short differentiation time, no animal-derived component, no need for animal-derived cells to serve as the feeder layer during differentiation, no need to formEB, and no need for repeated replacement of the culture solution components in differentiation, and can acquire a large number of high purity neural stem cells within a short time.

The invention discloses a culture medium for culturing neural stem cells on the basis of peripheral blood mononuclear cells. The culture medium comprises components as follows: a DMEM / F12 culture medium and a neurobasal medium in a volume ratio being 1:0.8-1.2 as well as an adenylate cyclase activator, a serum substitute, L-ascorbic acid, an L-glutamine derivative, an ALK inhibitor, a GSK-3 inhibitor, an ALK-2,3,6,AMPK inhibitor and an ALK-4,5,7 inhibitor. The invention further discloses a method for culturing the neural stem cells on the basis of the peripheral blood mononuclear cells. With adoption of the culture medium, the neural stem cells can be obtained from the peripheral blood mononuclear cells as the raw material through directional differentiation culture, materials are taken conveniently and free of quantitative restriction, and moral controversy can be avoided.

A drug containing, as an active ingredient, a compound represented by ALK inhibitors such as brigatinib, AP26113-analog, and AZD3463 has been found to be effective against a non-small cell lung cancer having a point mutation at C797S in EGFR which has acquired a resistance to chemotherapy agents. Further, the drug used in combination with an anti-EGFR antibody demonstrates a notable suppression effect on the tumor growth. The drug has a potential to be a therapeutic agent effective against a non-small cell lung cancer which is resistant to gefitinib, a first generation therapeutic agent and osimertinib, a third generation therapeutic agent.

A pharmaceutical combination comprising an ALK inhibitor, in free form or a pharmaceutically acceptable salt thereof, and a SHP2 inhibitor, in free form or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, for simultaneous or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

The present invention relates to a compound represented by a formula (I), a pharmaceutical composition and a preparation method thereof, wherein the compound can be used as an ALK inhibitor to treat ALK-mediated diseases. The invention further relates to the preparation method of the compound represented by the formula (I), and applications of the compound represented by the formula (I) and the pharmaceutical composition thereof in preparation f drugs for treatment of ALK-mediated diseases. The formula (I) is defined in the specification.

The invention discloses a spiro aryl sulfone compound, and especially relates to the compound represented by the formula (I) as an ALK inhibitor.

A method of treating patients suffering from cancers driven by deregulated Human Epidermal Growth Factor Receptor (HER1 / Human EGFR) comprising administering to a patient in need of such treatment a flexible and active regimen for combining Anaplastic Lymphoma Kinase Inhibitors (ALK Inhibitors) and anti-EGF antibodies for inhibition of the pathway activated by EGF-EGFR binding (mAb). The anti-EGF antibodies can be produced by active immunization or provided passively by the administration of antibodies that are anti-EGF. The method comprises ALK Inhibitors administered according to a continuous regimen based on an average daily dose in the range of 10 to 250 mg and the mAb is co-administered either actively or passively according to a dosing regimen achieving a therapeutic effective amount repeated thrice, twice or once a week, once in two weeks, once in three weeks or at least once monthly.

The invention relates to the field of medicinal chemistry, and in particular relates to medical applications of compounds (1-20) and medicinal compositions containing the compounds, especially the applications as an ALK inhibitor. The structural formulas of the 20 compounds are shown in the description.

The invention discloses a culture solution for culturing neuronal cells based on peripheral blood mononuclear cells. The culture solution comprises a DMEM / F12 basic culture medium and a nerve cell culture medium which have a volume ratio of 1 to (0.8 to 1.2), nerve growth factor, an adenylate cyclase activator, a serum substitute, L-ascorbic acid, L-glutamine derivatives, an ALK inhibitor, a GSK-3 beta inhibitor, a GSK 3 alpha inhibitor, an ALK-2, 3, 6, AMPK inhibitor and a TGF-beta R inhibitor. The invention also discloses a method for culturing the neuronal cells based on the peripheral blood mononuclear cells. The culture solution can be used for carrying out directional differentiation culture by taking the peripheral blood mononuclear cells as a raw material so as to obtain the neuronal cells. The culture solution is convenient in material obtaining and free from quantitative limitation, and can avoid moral controversy.

The invention provides a method for separating and culturing peripheral blood mononuclear cells, and relates to the field of biotechnology cell culture. The separation and culture method of the peripheral blood mononuclear cells comprises the following steps: S1, collecting peripheral blood, S2, carrying out centrifugal separation, S3, extracting peripheral blood mononuclear cells, S4, purifying the peripheral blood mononuclear cells, S5, preparing a cell culture medium, S6, carrying out cell culture, and S7, performing preservation. An ALK inhibitor and a GSK-3 inhibitor are arranged, cytopathy in a cell culture process can be inhibited, excessive activation of pathological cells is prevented and rapid proliferation is carried out, animal serum is not added in the culture process, so thatthe possibility of obtaining viruses from animals in the culture process is reduced, the safety in the culture process is ensured, and peripheral blood mononuclear cells are cleaned and purified formultiple times after separation is completed, so that the cultured cells basically do not contain other impurity cells, and the cultured cells are relatively pure.

Described herein are compositions, kits, and methods for determining whether subjects having cancer(s) positive for ALK mutations are likely to respond to treatment with an ALK inhibitor and / or whether a patient having such cancer(s) is likely to have a relatively slower disease progression. Further described are methods for prognosing a time course of disease in a subject having such cancer.