30 results about "PDGFRA" patented technology

The present invention provides a computer-implemented method for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy, the method comprising: providing a mutation profile of the subject, said profile comprising the presence or absence of cancer-specific mutations at one or more locations in at least five genes selected from the group consisting of: NF1, STK11, TSC2, BRCA2, BRAF, STAG2, U2AF1, BRIP1, PDGFRA, CTNNA1, PDK1, FGF10, and FLT1; analysing the mutation profile to classify the profile as matching the mutation profile of a response signature or a resistance signature, wherein the subject is predicted to be likely to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the response signature and is predicted to be likely not to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the resistance signature. Also provided are related methods and systems for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy.

The invention provides a method for purifying ovarian progenitor cells and application of the ovarian progenitor cells to in-vitro generation of steroid secretion cells, and belongs to the technical field of biology. The method for purifying the ovarian progenitor cells comprises the following steps: digesting, filtering and washing an ovary, purifying through a magnetic bead or flow cytometry sorting procedure, and screening to obtain the ovarian progenitor cells, a marker used in the purification process is LY6A, LGR5 or PDGFRA (Platelet Derived Growth Factor Receptor A). Experimental results show that the PDGFRA < + > progenitor cells and the LY6A < + > progenitor cells can form androgen synthetic cells for expressing CYP11A1 and CYP17A1; and the LGR5 < + > progenitor cells can only form progestational hormone synthetic cells which express CYP11A1 but do not express CYP17A1.

The present application belongs to the field of biomedical technology, and particularly relates to an axial length and growth trend evaluation method of eye axis based on PDGFRA gene and a PDGFRA enzyme activity control agent. The method comprises the following steps: 1) collecting an eye biological sample of a subject; 2) based on the expression level of PDGFRA gene of platelet-derived growth factor receptor alpha in the collected biological sample; 3) based on the expression level, calculating the axial length of the eye axis according to the quantitative relationship between the expression amount of PDGFRA and the axial length of the eye axis, and predicting the growth trend of the axial length of the eye axis through additional calculation. The technical scheme of the present application can effectively detect and evaluate the axial length of the eye axis, effectively judge the growth trend of the axial length of the eye axis, and directly and efficiently control the axial length of the eye axis and its growth trend through the existing drug components.

The application discloses biomarkers, kits and application thereof for breast cancer detection. Specifically disclosed are application of biomarkers and / or substances for detecting the biomarkers in breast cancer gene detection, wherein the biomarkers include 13 gene mutation sites, namely AKT1, EGFR, ERBB2, ERBB3, ESR1, FBXW7, KRAS, MTOR, PDGFRA, PIK3CA, PTEN, SF3B1 and TP53. The application also discloses a breast cancer gene mutation detection method, which covers 173 mutation sites of 13 genes, reduces the number of detection reactions by designing a primer panel, realizes simultaneous coverage of more gene mutation sites by using fewer primers, and completes library construction through one round of PCR amplification, is short in operation time, and is high in sensitivity and can reach 0.2%.

The invention relates to a CSF1R family inhibitor with a structure as shown in a formula (Ia) or a formula (Ib) and application of the CSF1R family inhibitor in pharmacy. The compound disclosed by the invention can be widely applied to preparation of drugs for treating tumors, autoimmune diseases, metabolic diseases or metastatic diseases related to CSF1R, PDGFRa and KIT kinase; the compound can be used for preparing medicines, especially medicines for treating ovarian cancer, pancreatic cancer, prostate cancer, breast cancer, cervical cancer, glioblastoma, multiple myeloma, metabolic diseases, neurodegenerative diseases, metastasis of primary tumor sites or bone metastatic cancer, and is expected to be developed into a new generation of CSF1R, PDGFRa and KIT kinase inhibitor medicines. # imgabs0 #

The present disclosure provides methods and intermediates for making Compound A or a pharmaceutical salt thereof, and / or a solvate of, which are useful as methods and intermediates for producing compounds for treating diseases and conditions related to mutant KIT and PDGFRA.

Crystalline Forms of Compound (I):pharmaceutically acceptable salts thereof and solvates of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions associated with oncogenic KIT and PDGFRA alterations using the same, and methods for making Compound (I) and crystalline forms thereof are also disclosed.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecule compounds having a 6,6-heterocyclic structure (e.g., compounds having a naphthyridine, pyrido-pyridazine, pyrido-pyrazine, quinoline, pyrazino-pyridazine, pyrimido-pyrimidine, quinazoline, quinoxaline or cinnoline ring system) which function as inhibitors of DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8 / 19, PI3K, PDGFrA / B, mTOR, WNT, homeodomain-interacting kinases (HIPKs), and / or CMGC kinases leading to inhibition of WNT signaling, and their use as therapeutics for the treatment of Alzheimer's disease, down syndrome, Parkinson's disease, Huntington's disease, diabetes, autoimmune diseases, inflammatory disorders (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colorectal cancer and metastatic colorectal cancer (e.g., metastatic colorectal cancer in the liver)), and other diseases.

The presently disclosed subject matter relates to antibodies and antigen-binding fragments that bind specifically to phosphorylated PDGFRA, and methods of treating cancer expressing MAN2A1-FER which ectopically phosphorylates PDGFRA. MAN2A1-FER can be expressed in liver cancer, prostate cancer, brain cancer, glioblastoma multiforme, breast cancer, lung cancer, non-small cell lung cancer, colon cancer, and renal cell carcinoma.

The present disclosure provides compounds of Formula I, pharmaceutical salts thereof, and / or solvates of any of the foregoing which are useful for treating diseases and conditions related to mutant KIT and PDGFRa and present an advantageously non-brain penetrant profile for treating diseases and conditions related to mutant KIT and PDGFRa. The present disclosure also provides methods for treating gastrointestinal stromal tumors and systemic mastocytosis.

The invention provides application of OPC-like cell detection in prediction of glioblastoma with epilepsy. Specifically, the invention provides an application of a detection reagent of OPC-like cell markers PDGFRA and EGFRvIII in prediction of epilepsy of people with glioblastoma. The invention has an application prospect in the field of diagnosis and treatment of diseases of glioblastoma with epilepsy.

The present disclosure provides methods and intermediates for producing Compound A, or a pharmaceutical salt thereof and / or a solvate thereof, which are useful as methods and intermediates for manufacturing compounds for treating diseases and conditions associated with mutant KIT and PDGFRA. JPEG2024508329000030.jpg7265

The present application relates to the use of PDGFRA inhibitors in the preparation of a medicament for treating astrocytic tumors. The present application first discovers and proves by experiments that PDGFRA inhibitors can significantly inhibit the excessive proliferation of astrocytic tumor cells, but do not affect the proliferation of normal cells of the same type, thereby can alleviate, improve or treat astrocytic tumors, or delay the progression of astrocytic tumors, and thus are expected to become a candidate therapeutic drug for astrocytic tumors, and have a great clinical application prospect.

A composition of INFRA cells is described. The composition includes human muscle stem cells (SCs) expressing the transcription factor PAX7 and lacking the expression of the transmembrane receptor PDGFRA, wherein at least 70% of the population of human muscle SCs are PAX7+ and PDGFRA-. Methods of preparing the INFRA cell compositions, and methods of using the INFRA cells to treat muscle injury are also described.

The present invention is in the field of medicinal chemistry. In particular, the present invention relates to a new class of small molecule compounds having a 6,6-heterocyclic structure (e.g., naphthyridine, pyrido-pyridazine, pyrido-pyrazine, quinoline, pyrazino-pyridazine, pyrimido-pyrimidine, quinazoline, quinoxaline, or cinnoline ring system) that inhibit the activity of DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8 / 19, PI3K, PDGFrA / B, mTOR, WNT, homeodomain-interacting kinase (HIPK), and / or CMGC-kinase. The present invention relates to compounds that function as inhibitors of WNT enzymes, leading to the inhibition of WNT signaling, and the use of those compounds as therapeutic agents for the treatment of Alzheimer's disease, Down's syndrome, Parkinson's disease, Huntington's disease, diabetes, autoimmune diseases, inflammatory disorders (e.g., airway inflammation, osteoarthritis (e.g., knee-related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colon cancer and metastatic colon cancer (e.g., metastatic colon cancer to the liver)), and other diseases.

A method of differentiating nonhuman primate induced pluripotent stem cells (iPSCs) to oligodendrocytes is provided. The method may include providing a modified vector comprising a piggyBac vector backbone that expresses one or more differentiation factor genes, including SOX10, OLIG2, and NKX6-2. The piggyBac vector backbone may comprise one or more terminal inverted repeats and one or more transposase recognition sites configured to interact with a piggyBac transposase to mediate genomic integration at TTAA or noncanonical target sequences. The vector may further include a selectable marker and a promoter for regulated expression. The modified vector may be introduced into nonhuman primate iPSCs, for example from Macaca fascicularis, by electroporation and used in a feeder-free differentiation workflow. The resulting differentiated cells may be identified by expression of oligodendrocyte-associated markers including O4, O1, PDGFRA, MOG, GALC, CNPase, and myelin basic protein (MBP).

The invention provides a diagnostic marker combination for glioblastoma prognosis. The diagnostic marker combination comprises a three-structural-domain protein 21 (TRIM21) and a platelet-derived growth factor receptor alpha (PDGFRA) and application of the diagnostic marker combination. According to the invention, the fact that the PDGFRA and the TRIM21 are jointly used as a group of biomarkers is proposed for the first time, and a new thought is provided for performing typing diagnosis, treatment scheme selection or prognosis evaluation on the glioblastoma. And a more accurate choice is provided for selection and application of the PDGFRA inhibitor in personalized treatment of patients with glioblastoma.

A composition of INFRA cells is described. The composition includes human muscle stem cells (SCs) expressing the transcription factor PAX7 and lacking the expression of the transmembrane receptor PDGFRA, wherein at least 70% of the population of human muscle SCs are PAX7+ and PDGFRA-. Methods of preparing the INFRA cell compositions, and methods of using the INFRA cells to treat muscle injury are also described.

Provided are methods of targeting patient-specific oncogenes in extrachromosomal DNA (ecDNA) to treat glioma in a human. The present methods include identifying a drug that targets against an oncogene present in ecDNA of a human suffering from glioma, such as glioblastoma. The identified oncogenes present in ecDNA include MET, MET / CAPZA2, MDM2, CDK4, SOX2, PIK3CA, MECOM, PDGFRA, EGFR, MYCN, MYC, TERT, SMARCA4, RP56, FBXW7, CDK6, CCND2, ERBB2, BRCA1, and BAP1. The present methods include identifying a drug targeted against the ecDNA oncogene, which drug inhibits the function of the identified oncogene, so as to inhibit tumor growth or progression of the glioma in the human. Also provided are PDX mouse models to further identify and / or confirm patient-specific drugs that target the identified oncogene(s) present in ecDNA. Also provided are methods of diagnosing gliomas or recurrent gliomas and methods of screening or monitoring for recurrence of gliomas. Further provided are methods of validating a predicted presence of ecDNA in a brain tumor using fluorescence in situ hybridization (FISH). Also provided are methods of screening drug candidates for a patient by implanting different identified drugs that target an identified oncogene into PDX mouse models.

The disclosure relates to methods of using locally administered formulations of a selective inhibitor of VEGFR2 and / or FGFR1, locally administered formulations of a PPAR-gamma agonist, or locally administered formulations of a PPAR-gamma agonist and a PDGFRA / B, VEGFR2 and / or FGFR1 inhibitor for reducing or reversing atrophy of dermal adipose and / or thinning of the skin in a subject.

This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecule compounds having a 6,6-heterocyclic structure (e.g., compounds having a naphthyridine, pyrido-pyridazine, pyrido-pyrazine, quinoline, pyrazino-pyridazine, pyrimido-pyrimidine, quinazoline, quinoxaline or cinnoline ring system) which function as inhibitors of DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8 / 19, PI3K, PDGFrA / B, mTOR, WNT, homeodomain-interacting kinases (HIPKs), and / or CMGC kinases leading to inhibition of WNT signaling, and their use as therapeutics for the treatment of Alzheimer's disease, down syndrome, Parkinson's disease, Huntington's disease, diabetes, autoimmune diseases, inflammatory disorders (e.g., airway inflammation, osteoarthritis (e.g., knee related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colorectal cancer and metastatic colorectal cancer (e.g., metastatic colorectal cancer in the liver)), and other diseases.

The present technology includes an isolated population of endothelial progenitor cells (EPCs) comprising PROCR + / -PDGFRA + / -EPC and a population of mesenchymal stem cells (MSCs), as well as methods of preparation and use thereof in the treatment of hypoxic ischemic encephalopathy (HIE) or brain injury in a subject.

A peptide construct for targeting PDGFRA includes diagnostic or therapeutic moiety which includes a chelator and a radionuclide. Also disclosed are diagnostic and therapeutic methods using the peptide constructs for diagnosing, imaging or treating cancer, particularly carcinoma of the thyroid, GIST, colon, breast, sarcoma, glioblastoma, or lymphoma.

Materials and methods for stratifying and treating cancers and to methods of identifying / selecting patients for treatment of cancer with tyrosine kinase inhibitors are disclosed. Gene expression profiles, TP53 mutations and FGFR1 and PDGFRA expression used to identify / select / stratify the cancers and patients are also disclosed.

The present disclosure provides compounds of Formula I, pharmaceutical salts thereof, and / or solvates of any of the foregoing, which are useful for treating diseases and conditions related to mutant KIT and PDGFRα and present an advantageously non-brain penetrant profile for treating diseases and conditions related to mutant KIT and PDGFRα. The present disclosure also provides methods for treating gastrointestinal stromal tumors and systemic mastocytosis.

The present invention is in the field of medicinal chemistry. In particular, the present invention relates to a new class of small molecule compounds having a 6,6-heterocyclic structure (e.g., naphthyridine, pyrido-pyridazine, pyrido-pyrazine, quinoline, pyrazino-pyridazine, pyrimido-pyrimidine, quinazoline, quinoxaline, or cinnoline ring system) that inhibit the activity of DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK3, CLK4, CDK7, CDK8 / 19, PI3K, PDGFrA / B, mTOR, WNT, homeodomain-interacting kinase (HIPK), and / or CMGC-kinase. The present invention relates to compounds that function as inhibitors of WNT enzymes, leading to the inhibition of WNT signaling, and the use of those compounds as therapeutic agents for the treatment of Alzheimer's disease, Down's syndrome, Parkinson's disease, Huntington's disease, diabetes, autoimmune diseases, inflammatory disorders (e.g., airway inflammation, osteoarthritis (e.g., knee-related osteoarthritis)), cancer (e.g., glioblastoma, prostate cancer, metastatic breast cancer, metastatic lung cancer, multiple myeloma, secondary metastatic tumors of the brain, colon cancer and metastatic colon cancer (e.g., metastatic colon cancer to the liver)), and other diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to application of avatinib in preparation of a medicine for preventing or treating central nervous system demyelination diseases. A treatment choice with a brand new action mechanism is provided for patients with central nervous system demyelination diseases which have poor curative effects on multi-line correction treatment drugs in the past, and pathological links which are not involved in existing treatment are covered by targeting PDGFRA and KIT related pathways, so that symptoms are improved, and disease progression is delayed. Therefore, the invention has wide clinical application prospect and commercial development value.

The invention belongs to the technical field of biological medicines, and relates to application of a CXCL14 inhibitor in preparation of a medicine for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the sex difference of the abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and a receptor CXCR4 thereof, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress process of the abdominal aortic aneurysm, and reduces the collagen degradation and elastic fiber destruction degrees, thereby inhibiting the pathological progress of the abdominal aortic aneurysm. The invention provides a new target spot and a medicine composition for precise treatment of male abdominal aortic aneurysm, and has a definite clinical application value.

The present application relates to a CSF1R family inhibitor having the structure of formula (Ia) or formula (Ib) and its pharmaceutical application. The compound of the present application can be widely applied to the preparation of a drug for treating tumors, autoimmune diseases, metabolic diseases or metastatic diseases related to CSF1R, PDGFRa and KIT kinases, in particular, a drug for treating ovarian cancer, pancreatic cancer, prostate cancer, breast cancer, cervical cancer, glioblastoma, multiple myeloma, metabolic diseases, neurodegenerative diseases, metastasis of primary tumor sites or bone metastatic cancer, and is expected to develop into a new generation of CSF1R, PDGFRa and KIT kinase inhibitor drug.

The present disclosure provides compounds of Formula (I-0), pharmaceutically acceptable salts thereof, and / or solvates of any of the foregoing, for use in the treatment of diseases and disorders associated with mutant KIT and PDGFRa, and exhibit advantageous non-brain penetration properties for the treatment of diseases and disorders associated with mutant KIT and PDGFRa. The present disclosure also provides methods for the treatment of gastrointestinal stromal tumors and systemic mastocytosis.