66 results about "Reversible inhibition" patented technology

The present invention relates to a method of treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour, for instance an activating mutation of the EGFR or a mutation responsible for resistance or the emergence of acquired resistance to treatment with reversible EGFR and / or HER2 inhibitors or irreversible inhibitors such as CI-1033, EKB-569, HKI-272 or HKI-357, comprising administering an effective amount of the irreversible EGFR inhibitor BIBW2992 (1) 4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline, to a person in need of such treatment, optionally in combination with the administration of a further chemotherapeutic agent, in combination with radiotherapy, radio-immunotherapy and / or tumour resection by surgery, and to the use of a BIBW 2992 (1) for preparing a pharmaceutical composition for the treatment of patients suffering from cancer and harbouring mutations of EGFR in the tumour.

The present invention relates to compounds of the formulae I and Ia,wherein R0; R1; R3; R4; R22, Q; V, G and M have the meanings indicated in the claims. The compounds of the formulae I and Ia are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and / or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and / or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and / or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formulae I and Ia, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

Compounds of formula (I) wherein the groups are as defined in the description are disclosed. The compounds of formula (I) are endowed with reversible inhibiting activity of carnitine palmitoyl-transferase and are useful in the preparation of medicaments useful in the pathologies related to a hyperactivity of carnitine palmitoyl-transferase, such as hyperglycemia, diabetes and pathologies related thereto, heart failure, ischemia.

The invention modifies the U1 ribonucleoprotein (U1 snRNP) at the 5' end of its RNA so that it binds specifically to an mRNA of the gene to be inactivated, in such a way that its expression is inhibited. Gene inactivation is greater with the binding of several ribonucleoproteins to several binding sites on the 3' terminal exon of the mRNA of the gene to be in-activated, concretely at specific sites around the site of initiation of polyadenylation of said mRNA. This method is used for (i) inhibiting the expression of genes of unknown function so that they can be studied and (ii) inhibiting the expression of genes that are harmful to the cell.

The invention provides methods and compositions for rapid and reversible inhibition of platelet aggregation in human subjects in need thereof by administering compounds of the formula:alone or in combination with a second agent which can be aspirin or a thrombolytic agent.

The present invention relates to a novel method of inhibiting gap junction-mediated signaling in pyramid cells. Pyramidal gap junctions are quickly and reversibly inhibited by beta-amyloid or biologically active fragments thereof. The present invention also relates to the use of beta-amyloid as an anticonvulsant for the treatment of epilepsy and other pathological hypersynchrony conditions in humans and non-human animals.

Described herein are compositions comprising, and methods for using, biocompatible cold slurries and methods of administering the same to provide reversible inhibition of peripheral nerves in a subject in need thereof.

The present invention provides compositions and methods for reversibly inhibiting S-adenosyl-L-homocysteine (SAH) hydrolase. The compounds of the present invention can be used as an anti-hemorrhagic viral infection agent, an immunosuppressant, a homocysteine lowering agent, or an anti-neoplasm agent. The compositions and methods of the present invention can be used for the prevention and treatment of hemorrhagic virus infection, autoimmune diseases, autograft rejection, neoplasm, hyperhomocysteineuria, cardiovascular disease, stroke, Alzheimer's disease, multiple sclerosis or diabetes. The compound of the present invention and / or used in the present invention has the formula (I):wherein Z is selected from the group consisting of carbon and nitrogen,R1 and R2 are the same or different, and are selected from the group consisting of Hydrogen, hydroxy, alkyl, cycloalkyl, alkenyl, alkoxy, amino, aryl, heteroaryl, and halogen;R3 and R4 are the same or different and are selected from the group consisting of Hydrogen, alkyl, acetyl, alkenyl, aryl, and heteroaryl;X is selected from the group consisting of oxygen, nitrogen, and sulfur; andY is selected from the group consisting of hydrogen, a C1-10 alkyl group, alkenyl, vinyl, aryl, and heteroaryl, provided that the compound is not (4-adenine-9-yl)-2-hydroxybutanoic acid.

Methionine aminopeptidases catalyse the co-translational removal of amino terminal methionine residues from nascent polypeptide chains. A newly-discovered enzyme, designated methionine aminopeptidase type-3 (MetAP-3), has a substrate specificity which is similar to MetAP-1 and MetAP-2, although it is not inhibited by fumagillin, an irreversible inhibitor of MetAP-2. MetAP-3 also preferentially localizes to mitochondria, unlike MetAP-1 and MetAP-2, which accumulate in the cytoplasm. One embodiment of the present invention relates to human cDNAs encoding polypeptides comprising MetAP-3. Other embodiments of the invention relate to nucleic acid molecules derived from these cDNAs, including complements, homologues, and fragments thereof, and methods of using these nucleic acid molecules, to generate polypeptides and fragments thereof. Other embodiments of the invention relate to antibodies directed against polypeptides comprising MetAP-3, and methods to screen for compounds or compositions that preferentially or specifically effect the activity of polypeptides comprising MetAP-3.