23 results about "ALK inhibitor" patented technology

The invention relates to the field of cell biology, and particularly discloses a neural stem cell induced differentiation culture medium and application thereof in preparation of neural stem cells. The neural stem cell induced differentiation culture medium is composed of a basic culture medium and additives, wherein the additives are composed of an N-2 additive, a B-27 additive, glutamine, a human leukemia inhibiting factor, a GSK-3 inhibitor, an ALK inhibitor, a gamma-secretase inhibitor and a CDK8 inhibitor. The neural stem cell induced differentiation culture medium is clear and simple in component, does not need to use antibiotics, and does not contain animal-derived components. When the culture medium is used for carrying out differentiation induction on the human pluripotent stem cells, the human pluripotent stem cells can be induced and differentiated into the neural stem cells within a short time (6-7 days) without depending on pluripotent stem cell cloning and a single cell state, the nonuniformity of pluripotent stem cell cloning formation can be overcome, and the purity of the neural stem cells is improved.

The present disclosure relates to a macrocyclic compound represented by formula I, a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt, prodrug, solvate, polymorph, isomer and stable isotopic derivative thereof, a preparation method therefor, and a use thereof as a TRK, ROS1, c-Met, CSF1 and / or ALK inhibitor.

The present invention provides a method for producing hepatic stem cells, the method including a step for culturing hepatocytes in a medium containing a Wnt signaling promoting substance and an FGF signaling promoting substance. The present invention also provides a method for producing hepatic stem cells, the method including a step for culturing hepatic stem cells in a medium containing a Wnt signaling promoting substance, an FGF signaling promoting substance, and an ALK inhibitor.

The present invention provides a method of treating ALK-negative / LTK-positive cancer in a subject, comprising administering to the subject a pharmaceutically-effective dose of a linear inhibitor of ALK. The invention is of particular utility in treating multiple myeloma, including proteasome inhibitor-resistant multiple myeloma.

The present invention provides a method for producing neural crest cells from pluripotent stem cells, the method comprising: a step (1) of subjecting pluripotent stem cells to suspension culture in a culture medium containing an ALK inhibitor and a bone morphogenetic protein; and (2) performing suspension culture in a culture medium containing an ALK inhibitor and a GSK-3beta inhibitor.

Disclosed herein are methods for identifying a subject as having NSCLC that is predicted or is likely to respond to treatment with an ALK inhibitor, for example crizotinib. The methods include identifying a sample including NSCLC tumor cells as ALK-positive or ALK-negative using immunohistochemistry (IHC) and scoring methods disclosed herein. A subject is identified as having NSCLC likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-positive and is identified as having NSCLC not likely to respond to treatment with an ALK inhibitor if the sample is identified as ALK-negative. According to certain embodiments of the methods, subjects predicted to respond to an ALK inhibitor may then be treated with an ALK inhibitor such as crizotinib.

A culture medium and a culture method for constructing prostate cancer organoids are provided. The culture medium includes a basic culture medium, and the following components with final concentrations: R-spondin1 15-200 ng / mL, Noggin 20-150 ng / mL, FGF2 5-15 ng / mL, FGF10 1-10 ng / mL, CHIR99021 0.5-1 μM, ALK inhibitor 0.25-1 μM, ROCK inhibitor 5-30 μM, nicotinamide 5-10 mM and sodium pyruvate 0.5-3 mM. The present culture medium and culture method can effectively improve the survival rate and formation efficiency of organoids through the compounding of each component.

Provided are a macrocyclic ALK inhibitor, a preparation method therefor, a pharmaceutical composition containing the inhibitor, and the use thereof in the prevention or treatment of ALK-related diseases.

The invention relates to the technical field of biomedicine, in particular to a third-generation ALK TKI drug loratinib drug-resistant cell strain as well as a construction method and application thereof, the drug-resistant cell strain is a loratinib-resistant human non-small cell lung cancer cell strain H3122 LS and is preserved in Guangdong Microbial Culture Collection Center on July 25, 2025, and the preservation number is GDMCC No: 66760. According to the invention, an EML4-ALK fusion driven H3122 cell is treated by using a third generation of ALK TKI loratinib, a cell with high drug resistance to loratinib is formed through induction, and it is found that the drug-resistant cell loses EML4-ALK fusion variation. At present, the drug-resistant mechanism of the ALK inhibitor is not clarified clinically, and the construction of the drug-resistant cell and the discovery of the drug-resistant mechanism are beneficial to guiding clinical discovery of a new potential drug-resistant mechanism; a new drug-resistant related driver gene or signal pathway is found, and an experimental basis is provided for subsequent treatment strategy selection of a drug-resistant patient.

The invention provides a crystal form of a compound shown in a formula I or a salt thereof. The crystal form is an equivalent mesylate crystal form A of a compound as shown in a formula I, a crystal form D of the compound as shown in the formula I, an equivalent maleate crystal form A of the compound as shown in the formula I, an equivalent tartrate crystal form C of the compound as shown in the formula I, an equivalent citrate crystal form B of the compound as shown in the formula I or an equivalent succinate crystal form D of the compound as shown in the formula I; the crystal form has one or more of the following advantages: high crystallinity, good stability, low hygroscopicity, high solubility and high bioavailability. # imgabs0 #

The present invention discloses a nucleotide sequence targeting the KMT2C gene and its application in preparing cells resistant to ALK inhibitors, belonging to the technical field of genetic engineering. The nucleotide sequence targeting the KMT2C gene is shown as SEQ ID NO.1 to SEQ ID NO.6. By reducing the expression of KMT2C, the present invention can obtain a cell model resistant to ALK inhibitors.

The present invention relates to 5-(4-fluorophenyl)-2,3-dihydro-1H-imidazo[1,2-a]imidazole derivatives of formula (I) as ALK5 inhibitors (transforming growth factor 3 (TGF3) type 1 receptor) for the treatment of fibrosis, such as e.g. pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), hepatic fibrosis, renal fibrosis, ocular fibrosis, cardiac fibrosis, arterial fibrosis and systemic sclerosis. An example with good activity is e.g. example 5: 2-(dimethylamino)-N-(2-fluoro-5-(6-(6-methylpyridin-2-yl)-2,3-dihydro-1H imidazo[1,2-a]imidazol-5-yl)phenyl)acetamide (Formula IA). Pharmacological data is provided: (Table 3)TABLE 3Example NoALK5 pKi2, 9, 10≥9.01, 3, 4, 7, 8, 11, 12, 148.1-8.95, 6, 137.5-8.0

Disclosed herein are CD70-targeted treatments for RAS, RET, and ALK mutant cancers. The treatments are effective for preventing RAS, RET, and ALK inhibitor resistance, as well as for treating cancers that have developed resistance to RAS, RET, and ALK inhibitors. The present disclosure provides a method for treating a RAS, RET, or ALK mutant cancer in a subject comprising administering a CD70-targeted therapy to the subject, thereby treating the RAS, RET, or ALK-mutant cancer in the subject.

Compositions are provided for obtaining and / or culturing human normal tissue-derived organoids or human tumor tissue-derived organoids, comprising an ALK inhibitor (e.g., LDN214117), a WNT agonist (e.g., CHIR), an EGF agonist (e.g., EGF), and an FGF agonist (e.g., FGF2), optionally an IKK [epsilon] inhibitor.

A method of treating a patient suffering from a cancer driven by a dysregulated human epidermal growth factor receptor (HER1 / human EGFR) comprising administering to a patient in need of such treatment a flexible proactive regimen to combine an anaplastic lymphoma kinase inhibitor (ALK inhibitor) with an anti-EGF antibody (mAb) for inhibiting the pathway activated by EGF-EGFR binding. The anti-EGF antibody can be produced by proactive immunization or provided passively by administration of an anti-EGF antibody. The method comprises administering the ALK inhibitor according to a continuous regimen based on an average daily dose ranging from 10 to 250 mg, and co-administering the mAb, either proactively or passively, according to a dosing regimen that achieves a therapeutically effective amount repeated three times a week, twice or once, once every two weeks, once every three weeks, or at least once a month.

The invention discloses a composition for constructing an IOPN organ model, a model construction method and application. The composition for constructing the IOPN organoid model comprises an organoid model culture medium, and the organoid model culture medium comprises a penicillin-streptomycin double antibody solution, GlutaMAX, a serum-free supplement, Rspo-1, a Wnt activator, a growth factor, an HEPES buffer solution, N-acetyl-L-cysteine, a gastrin hormone, nicotinamide, forskolin, an ALK inhibitor, a ROCK inhibitor and the balance of a basic culture medium. The IOPN type organ model cultured by the composition for constructing the IOPN type organ model can maintain the original characteristics of tumors, provides a reliable biological model for pathological research and drug research and development of pancreatic tumors, and is convenient to operate and low in cost.

The current disclosure provides for methods for differentiating stem and progenitor cells into neural cells through an approach that excludes the use of inhibitors of the BMP4 pathway resulting in SMAD inhibition. Aspects of the disclosure relate to a method for differentiating stem or progenitor cells into neural cells, the method comprising (i) contacting the stem or progenitor cells with a differentiation composition; and (ii) culturing the cells in microwells to form spheroids. Further aspects relate to a method for differentiating stem or progenitor cells into neural cells, the method comprising (i) contacting the stem or progenitor cells with a differentiation composition, wherein the differentiation composition comprises one or more of the ALK inhibitors: DMH1, DMH2, K02288, A83-01, or combinations thereof; and (ii) culturing the cells in microwells to form spheroids. Also described is a neural cell, spheroid, a population of cells, or a population of spheroids produced by the methods of the claims.

The invention discloses a composition for constructing a complex PNET organ-like model, a model construction method and application. The composition comprises a penicillin-streptomycin double antibody solution, GlutaMax, a serum-free supplement, a Wnt signal channel activator, a human recombinant Noggin protein, a human recombinant FGF10 protein, HEPES, N-acetyl-L-cysteine, gastrin, nicotinamide, an adenylate cyclase activator, an ALK inhibitor, a ROCK inhibitor and a p38MAPK inhibitor. The composition provided by the invention comprises a plurality of growth factors required for vascularization growth of PNET organs, and can meet the requirements of PNET organ cells on nutrient substances and regulation and control substances in a complex structure growth process; in the culture process, a complex PNET organ-like biological model which is closer to the real tumor microenvironment of a human body and is more simulated and more comprehensive is developed, and the PNET organ-like biological model has wider and more important application value in the aspects of clinical diagnosis of PNET diseases, drug research, development and screening, precision medical treatment and the like.

The present invention provides a method for producing hepatocytes, said method comprising a step for carrying out suspension culturing of hepatoblasts in a medium that includes an oncostatin M receptor agonist, an ALK inhibitor, a cAMP agonist, and an adrenaline receptor agonist.

The present disclosure relates to methods and compositions for treating cancer with a macrocyclic indazole compound in combination with at least one other cancer therapeutic, such as a Bcl-2 inhibitor, a FLT3 inhibitor, a KRAS inhibitor, an ALK inhibitor, a PARP inhibitor, an EGFR inhibitor, a chemotherapy, and the like.

The present invention relates to a drug, a combination agent, a pharmaceutical composition or a preparation for treating or preventing ALK fusion gene positive cancer, comprising a combination of an ALK inhibitor and a TNKS inhibitor or comprising a pan-HER inhibitor in combination therewith, and a method for treating or preventing cancer, and a drug or the like that temporarily inhibits the growth of an ALK fusion gene-positive cancer that is resistant to an ALK inhibitor.

The present disclosure relates to methods and compositions for treating cancer in combination with a macrocyclic indazole compound and at least one other cancer therapeutic agent, such as a Bcl-2 inhibitor, an FLT3 inhibitor, a KRAS inhibitor, an ALK inhibitor, a PARP inhibitor, an EGFR inhibitor, chemotherapy, and the like.

The present invention relates to a drug, a combination agent, a pharmaceutical composition or a preparation for treating or preventing ALK fusion gene-positive cancer, which comprises an ALK inhibitor and a TNKS inhibitor in combination or comprises a pan-HER inhibitor in combination therewith, and a method for treating or preventing the cancer, as well as an agent for inhibiting the growth of ALK fusion gene-positive cancer which is resistant to the ALK inhibitor on a temporary basis, and the like.