72results about How to "Inhibit activity" patented technology

A new receptor for fibroblast growth factor has been cloned and expressed. The recombinant receptor is useful for inhibiting FGF activity, and for screening compounds for binding activity similar to that of FGF. A soluble, truncated recombinant receptor is also prepared, and is capable of binding FGF.

The present invention discloses compounds of Formula I or II, or pharmaceutically acceptable salts, esters, or prodrugs thereof:which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering to the subject a pharmaceutical composition comprising a compound of the present invention.

Disclosed are a 2,4,7-substituted thieno[3,2-d]pyrimidine compound having a protein kinase inhibition activity, a pharmaceutically acceptable salt, and a pharmaceutical composition for prevention and treatment of diseases caused by abnormal cell growth comprising the compound as an effective ingredient.Since the novel 2,4,7-substituted thieno[3,2-d]pyrimidine compound exhibits superior inhibition activity against various protein kinases involved in growth factor signal transduction, it is useful as an agent for preventing or treating diseases caused by abnormal cell growth.

A family of microRNAs, called the miR-15 family, which includes miR-195, are shown to be up-regulated during pathological cardiac remodeling and repress the expression of mRNAs required for cell proliferation and survival, with consequent loss of cardiomyocytes. Strategies to block expression of the miR-15 family in the heart as a treatment for diverse cardiac disease are provided.

The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B-RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formula (I): wherein: J is independently —O— or —NRN1—; RN1, if present, is independently —H or a substituent; RN2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH2)j-M-(CH2)k— wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently —O—, —S—, —NH—, —NMe—, or —CH2—; each of RP1, RP2, RP3, and RP4 is independently —H or a substituent; and additionally RP1 and RP2 taken together may be —CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently —CH2—, —NRN—, —C(═X)—, or —S(═O)2—; exactly one linker moiety is —NRN—, or: exactly two linker moieties are —NRN—; exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O)2—; or: exactly one linker moiety is —S(═O)2—, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NRN—; X is independently ═O or ═S; each RN is independently —H or a substituent; A is independently: C6-14carboaryl, C5-14heteroaryl, C3-12carbocyclic, C3-12heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

The present invention provides novel compounds and pharmaceutical compositions thereof, which at least partially activate PPARγ and may further inhibit the activity of the AT1 receptor. The novel compounds include certain substituted benzimidazole compounds of Formulae I and II, infra. The invention also provides methods of treating inflammatory and metabolic disorders and methods for screening compounds for the capability to treat or prevent an inflammatory or metabolic disorder.

The present invention provides protein kinase inhibitors comprising imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine compounds of the following structure (I) and (II):or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof, wherein R, R1, R2 and X are as defined herein. Compositions and methods for using the same in the treatment of cancer and other Pim kinase-associated conditions are also disclosed.

The present invention includes a PCSK9 activity inhibition assay system, kits, compositions and methods. The present invention includes a cell having a first vector capable of expressing a catalytic fragment of PCSK9, a second vector capable of expressing a prodomain of PCSK9 and a V5 protein with a detectable label. The V5 protein forms a fusion protein with the prodomain of PCSK9 and wherein cleavage of the prodomain by the catalytic fragment of PCSK9 releases a detectable signal.

Method of treating an individual exposed to and / or infected with a virus selected from the group consisting of: West Nile Virus, Japanese encephalitis virus, Kunjin virus Tick-borne encephalitis virus and Hepatitis C virus, are disclosed. The methods comprise administering to such individuals, a therapeutically effective amount of one or more compounds that inhibit CK2 activity, one or more compounds that inhibit CK2 expression or a combination thereof. Pharmaceutical compositions comprising therapeutically effective amount of one or more compounds that inhibit CK2 activity, one or more compounds that inhibit CK2 expression, or a combination thereof are also disclosed. Methods of inhibiting viral replication by a virus selected from the group consisting of: West Nile Virus, Japanese encephalitis virus, Kunjin virus Tick-borne encephalitis virus and Hepatitis C virus, using one or more compounds that inhibit CK2 activity, one or more compounds that inhibit CK2 expression and combinations thereof, are disclosed. Methods of identifying compound useful to treat infection by a virus selected from group consisting of: West Nile Virus, Japanese encephalitis virus, Kunjin virus Tick-borne encephalitis virus and Hepatitis C virus, and methods of identifying CK2 inhibitors are disclosed.

The present invention provides novel compounds described herein, such as of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and / or inhibit transcription in the subject.

In certain aspects, the present disclosure provides compositions and methods for increasing red blood cell and / or hemoglobin levels in a subject in need thereof. Subjects in need include, for example, subject having an anemia and subjects have an ineffective erythropoiesis disorder.

We have discovered a protein in humans, herein referred to as collagen like gene (CLG) product (SEQ ID NOS: 12 and 13), that is expressed in human prostate cancer and breast cancer cell lines but not in normal adult, placenta, lung, liver, skeletal muscle, kidney or pancreas tissues. We have also discovered that the level of CLG mRNA expression correlates positively with the metastatic potential of the cancer cell lines tested.

The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.

Low molecular weight protein tyrosine phosphatase (LMW-PTP) is identified as a novel diagnostic and therapeutic target in cancer diagnosis, prognosis and treatment. The invention provides diagnostic and treatment methods useful in connection with cancers expressing LMW-PTP and, optionally, EphA2 receptor. Also provided is a screening method that utilizes changes in the amount and / or activity of LMW-PTP to identify candidate cancer therapeutic agents that effectively target the oncoprotein EphA2.

The invention relates to compositions and methods for modulating cell signaling mediated by signal transducers and activators of transcription (STAT). The compositions target cellular STAT3 and STAT1 protein, particularly STAT3, for degradation via the ubiquitination pathway. Thus, the STAT inhibiting agents are useful for inhibiting STAT mediated signal transduction events, such as responses to IL6 and v-Src, any may be applied to treating diseases associated with activated STAT proteins, particularly STAT3 activity, such as cell proliferative disorders, inflammatory reactions, and autoimmune conditions.

The present invention is drawn to cyclic RGD peptides linked via a disulfide bond, where the terminal cysteines are preferably in the D configuration. These peptides target αvβ3 integrin on tumor cells and neovasculatures and function as targeting agents for tumor diagnostic imaging and therapy. Compared with the commonly used RGD ligands, compounds of the present invention have improved targeting efficacy and lower nonspecific binding to normal organs. Moreover, the compounds of the present invention can be functionalized to conjugate imaging payload without decreasing binding strength.

The invention discloses a green fertilizer for organic agricultural products, which is characterized by comprising the following components in parts by weight: 0.1-0.2 part of aschersonia powder, 15-25 parts of rape cake, 35-40 parts of chicken manure, 4-9 parts of earthworm manure, 8-13 parts of rape cake, 5-9 parts of wheat bran, 3-7 parts of yam, 1-3 parts of sucrose, 1-7 parts of agar, 70-95 parts of corn straw, 55-75 parts of bean straw, 25-35 parts of potato straw, 1-8 parts of ground phosphorite and 2-7 parts of oyster shell powder. The green fertilizer combines the effects of inorganic and organic fertilizers, more effectively provides an organic microorganism generation source for thoroughly improving soil and soil pH value, and can also produce an active substance to stimulate crop growth and fix nitrogen in the air.

Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure formula (I) enantiomers, diastereomers, solvates, salts, tautomers or prodrugs thereof wherein, A, W, X, Y and R1 are defined herein.

The present invention relates to rapid, quantitative, specific, high through-put methods for screening test substances for their ability to inhibit activity of an ouabain-resistant Na+-K+-ATPase involved in a variety of biological processes such as regulation of osmotic balance and cell volume, maintenance of the resting membrane potential, establishment of the ionic composition of cerebrospinal fluid and aqueous humor, electrical activity of muscle and nerve, and receptor-mediated endocytosis, cardiac muscle contractility, neurotransmitter metabolism and vascular muscle cell contraction. These methods can be employed to identify compounds for use in therapeutic applications for disease processes in which dysfunction of the Na+-K+-ATPase contributes to a pathological process. The present invention also includes kits which are used in the methods provided herein. The present invention further includes methods of treating or preventing diseases or disorders which are associated with dysfunction of the Na+-K+-ATPase.

Provided are an antibody which binds specifically PAR1 (protease activated receptor 1) or a fragment of the antibody which retains similar characteristics thereto; a composition containing the same for inhibiting the migration activity and invasion activity of cancer cells; and a medicinal composition for treating cancer and the like.

This invention provides a class of compounds which are useful for specifically inhibiting cyclin-dependent kinases. This class of compounds finds use in treating diseases resulting from inappropriate activity of cyclin-dependent kinases, including cancer, viral infections (e.g., HIV) neurodegenerative disorders (e.g. Alzheimer's disease), and cardiovascular disorders (e.g. atherosclerosis). Moreover, certain members of this class are particularly useful for inhibiting cyclin-dependent kinase 7 and are especially useful for the treatment of breast cancer.

A compound of the following formula:wherein R1, R2, R3, R4, R5, T, U, V, X, Y, Z, G, and Z are defined herein. It also discloses a method of treating an angiogenesis-related disorder, e.g., cancer or age-related macular degeneration, with such a compound.

The present invention relates to pharmaceutical compositions comprising at least 10 mg / mL of a Factor VII polypeptide (i); a buffering agent (ii) suitable for keeping pH in the range of from about 5.0 to about 9.0; at least one aromatic preservative (iii) in a concentration of at least 0.1 mg / mL; and at least one antioxidant (iv) in a concentration of at least 0.1 mg / mL; the composition optionally comprising further components, with the proviso that none of such further components are Factor VII polypeptide stabilizing agents selected from (a) metal-containing agents, wherein said metal is selected from the group consisting of first transition series metals of oxidation state +II, except zinc; and (b) stabilising agent comprising a —C(═N—Z1-R1)-NH—Z2-R2 motif.

Small molecule covalent inhibitors of DCN1 and compositions containing the same are disclosed. Methods of using the DCN1 covalent inhibitors in the treatment of diseases and conditions wherein inhibition of DCN1 provides a benefit, like oxidative stress-related diseases and conditions, neurodegenerative diseases and conditions, metabolic disorders, and muscular nerve degeneration, also are disclosed.

A method of inhibiting viral infection in a mammal in need of same, includes administering an effective amount of at least one of the compounds of FGI-103 which are represented by 273, 365 and 510 either prophylactically to prevent viral infection, or therapeutically following viral infection. These compounds appear to selectively inhibit Caspase 8 as a method of preventing infective viral particle release. They can be administered IV, IP, orally or via other conventional administration routes. The compounds are highly effective, requiring relatively low dosages on the order of 1 ng / kg-200 mg / kg of body weight.

The present invention relates to carbamate derivatives having RNase H, polymerase and / or HIV reverse transcriptase modulatory, and particularly, inhibitory activity. Included in the invention are the carbamate derivatives, compositions containing the derivatives, methods of synthesis of the derivatives, screening methods to identify the derivatives, and methods of treatment using the carbamate derivatives, including the treatment of HIV, AIDS and retrovirus-associated cancer.

Provided are a peptide comprising the amino acid sequence of DEAQETAVSSHEQD, the polynucleotide encoding it, the uses of said peptide for the treatment of the symptoms associated with pain and for the inhibition of the activity of influenza virus, and a pharmaceutical composition containing said peptide.

A method for inhibiting the activity of matrix metalloproteinase (MMP), inhibiting the expression of matrix metalloproteinase, inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK), and / or promoting the expression of collagen in a mammal is provided, and the method comprises administrating an effective amount of a Terminalia catappa leaf extract to the mammal.