13 results about "Activating mutation" patented technology

The application discloses application of Pemigatinib or a salt thereof in preparation of a medicine, and the compound is used for treating seborrheic keratosis, preferably seborrheic keratosis related to abnormal activation of a fibroblast growth factor receptor (FGFR) signal pathway, but is not limited to the above mechanism, and specifically, the medicine can inhibit or improve skin hyperplasia and hyperkeratosis lesions driven by FGFR3 gene activating mutation.

Hypomelanosis of Ito is a clinical term for patients with mosaic syndromes characterized by skin hypopigmentation and developmental disorders. The genetic causes of these rare diseases remain largely unclear. Here, we report that GNA13 is a new gene that causes Hypomelanosis of Ito. We identified an identical mutation in this gene in four unrelated patients exhibiting pigmentary mosaicism. In depth functional investigations revealed that this is an activatory mutation that alters the cytoskeleton and morphology of melanocytes via a hyperactivation of the RHOA / ROCK signalling pathway. Our results also indicate that this pathology does not necessarily originate from a decreased production of melanin, but can originate from a defect in melanosome transfer to keratinocytes due to cell shape alterations. Thus, our findings suggest for the first time a mechanism by which the clinical symptoms of patients with Hypomelanosis of Ito appear, and pave the path for new therapeutic approaches. Altogether, the present invention relates to a method for treating a patient suffering from hypomelanosis of Ito by administering a ROCK inhibitor and / or RHOA inhibitor.

A compound for use in treating a disease associated with activating mutations in RAS, or for use in treating a disease treatable by a reduction in RAS activity, is selected from a compound of Formula (I), salts and esters thereof. The compounds are particularly useful in treating cancer.

The present invention relates to the use of neocuproine, elesclomol, disulfiram and / or dithiocarbamate for use in treatment of cancer, optionally in combination with MAPK-pathway inhibitors in cancers carrying mutations that are recognized as MAPK-pathway activating mutations.

This invention discloses EGFR inhibitors, their preparation, and applications. Specifically, this invention relates to a 4-substituted-2-(N-(5-substituted allylamido)phenyl)amino)pyrimidine derivative of formula (I). This series of compounds exhibits activity against L858R EGFR mutants, T790M EGFR mutants, and exon 19 deletion activation mutants, and can be used to treat diseases mediated by EGFR mutant activity, either alone or in part. For example, they have wide applications in the prevention and treatment of cancer, especially non-small cell lung cancer, and hold promise for development into a new generation of EGFR inhibitors.

A growing number of patients presenting severe combined immunodeficiencies associated with Rac2 mutations have been identified in newborns. These mutations are associated with high frequency of infection, leukopenia and more rarely autoinflammatory features. Here, the inventors show that the Rac2 activating mutations activates the NLRP3 inflammasome leading to the secretion of IL-1β from macrophages depending on their activation strength. Therefore, inhibiting GasderminD (GSDMD) pathway should be considered as a potential treatment for these patients. The present invention relates to a method of treating Rac2 monogenic disorders in a subject in need thereof comprising the administration of an inhibitor of GasderminD (GSDMD).

The application discloses a kind of gastric adenocarcinoma transgenic mouse model construction method and its application, the construction method includes the following steps: using transgenic and hybridization technology, MYC gene expression quantity or MYC protein activity in mouse gastric mucosa layer epithelial cell is overexpressed or increased, KRAS gene mutant type in gastric mucosa layer epithelial cell is activated simultaneously, make Kras protein function abnormal, continuously in activated state, finally obtained mouse is gastric adenocarcinoma transgenic mouse model.The application constructs Myc gene overexpression and KRAS activation mutation double gene mutation mouse spontaneous gastric cancer animal model, method is simpler.This mouse model of gastric cancer tumorigenesis time is shortened, tumorigenic rate is as high as 100%, and tumorigenic effect is stable.And after induction, only in stomach tumorigenesis, tumorigenesis has high specificity.Pathological section and immunohistochemical staining determine that this animal model is adenocarcinoma in gastric cancer, has good clinical representativeness, can be applied to the application in later development or screening gastric cancer drug.

To provide methods and compositions for enhancing immune responses against cancer and pathogens.SOLUTION: The presently disclosed subject matter provides methods and compositions for enhancing immune responses against cancer and pathogens. The presently disclosed subject matter relates to cells comprising a c-Kit mutant, e.g., a c-Kit mutant comprising an activating mutation. The cell may further comprise an antigen recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)). The presently disclosed subject matter relates to the use of cells for treatment, e.g., treatment of cancer.SELECTED DRAWING: None

The invention discloses a nucleic acid inhibitor of a targeted thyroid stimulating hormone receptor and application. The nucleic acid inhibitor has high targeting property, and can accurately recognize TSHR and avoid off-target effect; the inhibition effect is strong, and the TSHR function can be obviously blocked under the micro-mole or even nano-mole concentration; as a nucleic acid molecule, the nucleic acid molecule does not cause obvious immune response and is suitable for long-term treatment; good biological stability: after chemical modification, excellent serum stability and tissue penetrating ability are achieved; the compound is suitable for various administration routes, is convenient for clinical transformation, and shows a wide clinical application prospect in treatment of various TSHR-mediated autoimmune and neoplastic diseases such as Graves diseases, thyroid-related eye diseases, TSHR activated mutation-driven thyroid cancer and the like. Especially for moderate and severe TED patients lacking effective specific targeted therapy means at present, the nucleic acid inhibitor is expected to become the first precise therapy for directly intervening the TSHR pathogenic core link.

The present invention provides polypeptides, polynucleotides, constructs and / or vectors comprising activating mutations in 53BP1. In particular, 53BP1 mutation at amino acid position 334 that makes the resulting protein resistant to phosphorylation and inactivation by GSK3β is provided. Also provided are lymphocytes comprising the mutant 53BP1 or a 53BP1 resistant to GSK3β phosphorylation and inactivation and methods of making and using the same.

The invention relates to a compound shown in a formula (I) and an isotope form, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a hydrate, a prodrug and a polymorph of the compound, the compound shown in the formula (I) can be used as an EGFR (epidermal growth factor receptor) inhibitor, can effectively inhibit EGFR with L858R mutation, exon 19 deletion mutation, C797S mutation, G724S mutation, L861Q and PACC mutation, and can be used for preparing an EGFR inhibitor. The compound has a good application prospect in the aspect of preparing medicines for treating cancers with EGFR activation mutation.

Methods for treating a B-cell malignancy in a human subject are described. The methods involve determining the presence or absence of a B-cell activating mutation in a gene(s) obtained from the subject. Methods include treatment with the compound of formula (I).

The present disclosure provides compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 39, 38, 39 JPEG2026500166000038.jpg48165 or a pharmaceutically acceptable salt thereof. The unit dosage forms described herein are suitable for oral administration. There remains a need for anti-estrogen agents that can completely inhibit estrogen receptors, including those encoded by both wild-type and mutant forms (e.g., those containing activating mutations) of the genes encoding estrogen receptor alpha (ERα) and estrogen receptor 1 (ESR1). Selective estrogen receptor modulators (SERMs) or degraders (SERDs) are particularly useful or promising tools for such treatment.