61 results about "Enzyme Inhibitor Agent" patented technology

The application discloses application of a BLM helicase inhibitor in treating myocardial hypertrophy. The application firstly finds that the BLM helicase inhibitor ML216 can significantly inhibit cardiac hypertrophy and myocardial cell fibrosis, thereby providing a new drug for treating myocardial cell hypertrophy diseases in the field, and providing practical experimental evidence and scientific basis for treating myocardial cell hypertrophy diseases, and having a good application prospect in treating myocardial hypertrophy and / or cardiac hypertrophy.

Described herein, inter alia, are GTPase inhibitors and uses thereof.

The application discloses a composition containing a peripheral vasodilator and a 5alpha-reductase inhibitor, effectively solves the transdermal inhibition of the peripheral vasodilator on the 5alpha-reductase inhibitor by adding a specific penetration enhancer, improves the transdermal rate of the active ingredients in the pharmaceutical composition by proportion adjustment, greatly improves the synergistic effect of local combined medication, avoids the side effects brought by oral 5alpha-reductase inhibitor, and improves the safety of the medicine.

This invention provides the use of β-glucuronidase in the preparation of an antidote for the prevention and / or treatment of zearalenone poisoning, and an antidote for the prevention and / or treatment of zearalenone poisoning, belonging to the field of feed additives. This invention, for the first time from the perspective of in vivo exposure control in animals, proposes a method to reduce the overall ZEN exposure level by inhibiting the activity of intestinal bacterial β-glucuronidase. The technical path is clear and highly operable. This is achieved through in vivo toxicokinetic parameters (AUC, C...). max Changes in (and / or MRT) objectively reflect a reduction in ZEN exposure levels in vivo, and the technical effects are quantifiable and verifiable. The β-glucuronidase inhibitors used in this invention are widely available, particularly suitable for the field of feed additives, and have promising application prospects.

The application provides a kinase inhibitor leading compound, a virtual screening method thereof and application of the kinase inhibitor leading compound in preparation of branched-chain alpha-keto acid dehydrogenase kinase inhibitors and / or drugs for treating diseases mediated by branched-chain alpha-keto acid dehydrogenase kinase. The virtual screening method provided by the application combines various virtual screening platforms to screen a large-scale compound library, improves the true positive rate of screening results, reduces the number of compounds needing experimental screening, and saves screening time and cost. In addition, the compounds I-III screened out with good binding affinity to BCKDK can be used in researches on targeting BCKDK to treat major diseases such as obesity, insulin resistance, maple syrup urine disease, neurological dysfunction, liver cancer, colorectal cancer and tumor cachexia.

Disclosed are combinations comprising a therapeutically effective amount of a menin-MLL inhibitor of Formula (I) or a pharmaceutically acceptable salt or a solvate thereof; and a therapeutically effective amount of at least one other therapeutic agent which is a hypomethylating agent, a cytidine deaminase inhibitor, a DNA intercalating agent, a pyrimidine analog, a purine analog, a kinase inhibitor, a CD20 inhibitor, an IDH inhibitor, an immunomodulatory agent or a DHODH inhibitor. Also disclosed are methods for treating a subject who has been diagnosed with cancer using such combinations. Compounds are represented by Formula (I) as follows:wherein the variables are defined herein.

The application belongs to the field of new use of drugs, and more particularly relates to application of 3-Deazaadenosine in preparation of a therapeutic drug for treating hypertrophic scars. 3-Deazaadenosine is an S-adenosylhomocysteine hydrolase inhibitor, and has antiviral, anti-inflammatory and other activities. Experiments show that the compound can significantly reduce the modification level of m6A in fibroblasts in hypertrophic scar tissue, inhibit the proliferation and migration of fibroblasts, promote the apoptosis of fibroblasts, and also can reduce the expression levels of Collagen I, Collagen III and alpha-SMA in fibroblasts. Therefore, the compound can be used for preparing a drug for relieving or treating hypertrophic scars, and has important clinical application value.

The present invention relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to processes for the preparation of said compounds.

This invention relates to 2-amino-4-methylquinazoline compounds, their preparation methods, uses, and pharmaceutical compositions. Specifically, it provides a compound represented by Formula I, which is a phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor that can be used to prevent and / or treat diseases related to PI3Kδ activity, such as tumors, autoimmune diseases, immunodeficiency diseases, inflammation, kidney diseases, cardiovascular diseases, metabolic / endocrine disorders, or neurological diseases.

This application relates to a PI3Kγ kinase inhibitor, which is a compound of formula (I) or a pharmaceutically acceptable salt, solvate, polymorph, ester, acid, isomer, metabolite, or prodrug thereof, wherein R1, R2, and R3 are as defined in the specification. This application also relates to the use of the PI3Kγ kinase inhibitor in the preparation of a medicament for treating diseases related to the activity of PI3Kγ kinase and related signaling pathways.

Disclosed are a pyrimidine carboxamide compound and an application thereof. Further provided are a pyrimidine carboxamide compound represented by formula (I), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, a mixture form thereof, or a pharmaceutically acceptable salt thereof. The compound can be used as a Vanin enzyme inhibitor, and can be used to prepare a drug for treating various diseases, including Crohn's disease, ulcerative colitis, and so on.

This invention discloses the application of a Trichinella spiralis cysteine ​​protease inhibitor in acute myocardial infarction and subsequent ventricular remodeling, belonging to the field of medicinal chemistry. This invention provides a drug that can prevent, alleviate, and / or treat acute myocardial infarction and subsequent ventricular remodeling. The active ingredient of this drug is the Trichinella spiralis cysteine ​​protease inhibitor cystatin, abbreviated as rTs-Cys. rTs-Cys can effectively delay acute myocardial infarction and inflammatory response in mice, reduce the infarct area, improve cardiac function deterioration, and reverse organ pathological damage, providing a new approach for the clinical treatment of acute myocardial infarction and subsequent ventricular remodeling.

The application belongs to the technical field of medicines, and relates to arylthiophene compounds, a preparation method and application thereof. The structural general formula of the arylthiophene compounds and pharmaceutically acceptable salts is shown as general formula I. The arylthiophene compound provided by the application has low preparation cost, and is simple and easy to implement. The arylthiophene compound provided by the application can be used as a vascular endothelial growth factor receptor 2 (VEGFR-2) kinase inhibitor, can be used for preparing a medicine for treating or preventing a tumor disease related to the vascular endothelial growth factor receptor 2 kinase, and has good application value and development and application prospect.

Provided herein are methods for reducing reactive microglia in a subject. Further provided herein are methods for treating a neurological disease, disorder, or condition in a subject. In some cases, the methods involve administering a 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor to the subject. In some cases, the 15-PGDH inhibitor can penetrate the blood-brain barrier.

This invention relates to an HPK1 kinase inhibitor, its preparation method, and its application. The HPK1 kinase inhibitor has the structure shown in formula (Ⅰ): (Ⅰ). Compared with the prior art, the HPK1 kinase inhibitor of this invention can effectively inhibit HPK1 activity, IC50... 50 The values ​​all reached nanomolar concentration levels, which is expected to improve the body's own immune function and weaken the immune escape effect of tumor cells.

Mastocytosis is a rare and heterogeneous disorder marked by the abnormal accumulation of mast cells (MCs) in various tissues. Tyrosine kinase inhibitors have shown limited efficacy, suggesting that additional molecular mechanisms are involved. The inventors showed the unexpected expression of AXL in neoplastic mast cells from patients with various forms of mastocytosis. This is particularly noteworthy as AXL expression had never been investigated in mast cells, whether neoplastic or normal. The study demonstrated the role of AXL, particularly in cooperation with KIT D816V to drive mast cell proliferation and resistance to therapies. In an embodiment, the AXL inhibitor bemcentinib (R428) is used in combination with the TKI midostaurin (PKC 412). The AXL-L197M identified in the ASM patient is pro-proliferative, and induces resistance to death in CD34-derived mast cells and in Ba-f3. Furthermore, the results also suggest that a combination of AXL inhibitors and BCL-2 inhibitors may be appropriate for the treatment of mastocytosis. In conclusion, AXL inhibitors can be thus suitable for the treatment of mastocytosis.

Disclosed herein are aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) inhibitors, pharmaceutical compositions, and methods of using these compounds to treat or prevent one or more ACMSD-related diseases, such as a muscle structural disorder, a neuronal activation disorder, a muscle fatigue disorder, a muscle mass abnormality disorder, a beta-oxidation disease, a metabolic disease, a cancer, a vascular disease, an ocular vascular disease, an ocular muscle disease, a liver disease, an inflammatory disease, or a kidney disease.

The present disclosure provides compositions comprising a polyamine synthesis inhibitor, a tyrosinase inhibitor and a corticosteroid, for reducing excess pigmentation. Also provided herein are methods of reducing excess pigmentation in a subject, comprising administering a composition comprising a polyamine synthesis inhibitor, a tyrosinase inhibitor and a corticosteroid to the subject, and uses of the claimed composition. In some examples, the polyamine inhibitor is an ornithine decarboxylase (ODC) inhibitor such as eflornithine (DFMO).

The present invention covers the use of chymase inhibitors in general and more in particular substituted bicyclically substituted uracils of general formula (I) as described and defined herein, and 3-methylbenzo-[b]thiophene)-2-sulfonamido derivatives of general formula (II) for manufacturing pharmaceutical compositions for the treatment or prophylaxis of stroke, pulmonary embolism, deep or superficial vein thrombosis, thrombotic microangiopathy, thrombotic microangiopathy in hypercoagulable states after infection, inflammation, transplantation, disseminated intravascular coagulation, vaccine-induced immune thrombotic thrombocytopenia, vascular access site thrombosis or occlusion.

Disclosed are a long-acting oral pharmaceutical comprising a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) and use thereof. Specifically, disclosed is a long-acting oral pharmaceutical formulation comprising a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, adjuvants, or excipients. The long-acting oral pharmaceutical formulation is suitable for administration at intervals of once every one week or longer, making it suitable for long-term administration in the treatment of chronic anemia.

The present application relates to the use of a combination of a Myt1 inhibitor and a Wee1 inhibitor in the treatment of cancer or induction of cell death. The synergistic effect of this combination results in a sub-therapeutic dosage or reduced dosing regimen of the Myt1 inhibitor, the Wee1 inhibitor, or both, relative to monotherapy with the Myt1 inhibitor or the Wee1 inhibitor alone.

The present invention relates to a RIPK1 kinase inhibitor comprising phensuximide or a pharmaceutically acceptable salt thereof as an active ingredient.

The application provides a preparation method of a microtubule affinity-regulating kinase inhibitor intermediate, and belongs to the technical field of chemical synthesis. The microtubule affinity-regulating kinase inhibitor intermediate is (1S, 6R)-2,2-difluoro-6-(((R)-1-phenylethyl)amino)cyclohexan-1-ol, and the (1S, 6R)-2,2-difluoro-6-(((R)-1-phenylethyl)amino)cyclohexan-1-ol is prepared by using L-camphor sulfonic acid as a resolving agent. When (1S, 6R)-2,2-difluoro-6-(((R)-1-phenylethyl)amino)cyclohexan-1-ol is prepared by purifying 2,2-difluoro-6-(((R)-1-phenylethyl)amino)cyclohexan-1-ol racemate, the operation is simple, the resolving can be realized by salification, the product can be obtained by filtering and dissociating, the product has high molar yield, low product loss, good product quality and high chiral purity of 99%, and the method is more suitable for industrial production.

The expression of the ATXN2 gene can be modulated to reduce the amount of ataxin-2 protein produced by a cell. This can be accomplished by administering to the cell an effective amount of an ATXN2 modulating agent. Screening was performed with 428,749 compounds for lowering expression of an ATXN2-luciferase reporter in HEK-293 cells, with a multiplexed cell viability assay to ensure target reduction in the absence of cytotoxicity. Secondary qHTS assays included a CMV-luciferase reporter expressed in HEK-293 cells as well as a biochemical assay using recombinant luciferase to detect inhibitors of the reporter enzyme. A diverse set of compounds were found to reduce ATXN2 expression, including compounds targeting HSP90, cardiac glycosides, NaK-ATPases and topoisomerases.

The present invention belongs to the technical field of chemical pharmaceuticals. Provided in the present invention are an aldosterone synthase inhibitor, and a preparation method therefor and the use thereof.  

The present disclosure provides compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK) (e.g., Janus kinase 2 (JAK2)) and / or cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 11 (CDK11)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

A method of treating a patient with intestinal radiation injury is disclosed. The method includes administering an effective amount of a geranylgeranyl transferase inhibitor to a patient with intestinal radiation injury. In one aspect, the geranylgeranyl transferase inhibitor is GGTi-298. In another aspect, the geranylgeranyl transferase inhibitor is GGTi-2133.

Novel crystalline forms of baxdrostat, methods for producing the same, pharmaceutical compositions containing the crystalline form, and the production of aldosterone synthase inhibitors, as well as the use of the crystalline form in the production of pharmaceuticals for the treatment of hypertension, primary aldosteronism, and chronic kidney disease.

The invention relates to a combination therapy. In particular, a Cell Division Cycle 7 kinase inhibitor (CDC7i) used in a combination therapy with: i) a Cyclin Dependent Kinase 8 inhibitor (CDK8i), and / or ii) a Cyclin C inhibitor (CCNCi); for use in the treatment or prevention of cancer in a subject.