Abstract: The present invention relates generally to methods for treating cancer. In one respect, the present invention relates to a method of treating a hematological cancer (e.g., multiple myeloma, leukemia, lymphoma) comprising administering to a patient in need thereof a therapeutically effective amount of a histone deacetylase inhibitor, for example, a histone deacetylase (HDAC) inhibitor as described herein, for example, PXD-101. In another respect, the present invention relates to a method of treating cancer (e.g., solid tumor cancer, e.g., rectal cancer, colon cancer, ovarian cancer; hematological cancer, e.g.

Abstract: The present invention pertains to the general field of chemical synthesis, and more particularly to methods for the synthesis of certain hydroxamic acid compounds, and in particular, (E)-N-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide, also known as PXD101 and Belinostat®, comprising, for example, the steps of: (SAF) sulfonamide formation; (PURC) optional purification; (AAA) alkenyl-acid addition, comprising: either (i): the steps of, in order: (ACAEA) alkenyl-carboxylic acid ester addition; (PURE) optional purification; and (CAD) carboxylic acid deprotection; or (ii): the step of: (ACAA) alkenyl-carboxylic acid addition; (PURF) optional purification; (HAF) hydroxamic acid formation; and (PURG) optional purification.

Abstract: Disclosed is a recombinant fusion protein containing an amino-acid sequence which comprises: (a) the Fc section or part of an Fc section of an immunoglobulin as component (A) or a functional variant of component (A); (b) the extracellular part of a TNF ligand or a partial sequence of the extracellular part of a TNF ligand as component (B) or a functional variant of component (B); and optionally (c) a transition area between component (A) and component (B), containing a linker.

Abstract: The present application discloses a compound of the formula (I) wherein Q is optionally substituted pyridyl; p is 0-6. Y is formulae (i), (ii) and (iii) where X is ?O, ?S and ?N—CN, r is 1-12, R is —Z-A, Z is a single bond, —S(?O)2—, >P?O, >C?O, —C(?O)NH—, and —C(?S)NH—; and A is hydrogen, C1-12-alkyl, C3-12-cycloalkyl, —[CH2CH2O]1-10—(C1-6-alkyl), C1-12-alkenyl, aryl, heterocyclyl, and heteroaryl; B is a single bond, —NRN—, —S(?O)2— and —O—; wherein RN is selected from hydrogen, C1-12-alkyl, C3-12-cycloalkyl, —[CH2CH2O]1-10—(C1-6-alkyl), C1-12-alkenyl, aryl, heterocyclyl, and heteroaryl; s is 0-6; and Cy is aryl, cycloalkyl, heterocyclyl, and heteroaryl. The compounds are useful for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT).

Abstract: The invention relates to oligomers of a dimer, trimer, quatromer or pentamer of recombinant fusion proteins. Said oligomers are characterized in that the recombinant fusion proteins have at least one component A and at least one component B, whereby component A contains a protein or a protein segment with a biological function, in particular with a ligand function for antibodies, for soluble or membranous signal molecules, for receptors or an antibody, or an antibody segment, and component B contains a protein or a protein segment which dimerizes or oligomerizes the dimer, trimer, quatromer or pentamer of the recombinant fusion protein, without the action of third-party molecules. The invention also relates to the use of dimers or oligomers of this type for producing a medicament, to the fusion proteins which cluster in dimers or oligomers and to their DNA sequence and expression vectors or host cells comprising this DNA sequence.

Abstract: This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C1-7alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the ?-position; and with the proviso that A is not benzimidazol-2-yl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

Abstract: The present invention relates to a new method, and the process to manufacture a medicament, for treating gout or pseudogout, comprising administering an effective amount of inhibitors blocking IL-1 or its maturation by the NALP3 inflammasome.

Abstract: This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: 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 HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

Abstract: Object matter of the invention is an optimized DNA sequence encoding the scFv(FRP5) antibody fragment. This novel sequence prevents the generation of the undesired by-product in the context of an scFv(FRP5)-ETA fusion protein, and possibly also other bacterially expressed scFv(FRP5)-containing fusion proteins. The DNA sequence of the scFv(FRP5) domain of scFv(FRP5)-ETA was modified by exchanging a distinct codon, thereby preventing an otherwise possible internal start of protein translation.

Abstract: The present invention relates to a method of treatment of a tumour cell which comprises administering to a subject in need of treatment an effective amount of a topoisomerase-II poison, e.g. etoposide, in combination with a bis-dioxypiperazine, e.g. dexrazoxane wherein said subject is further treated with radiation.

Abstract: Compounds can be used to act as inhibitors of enzymes having histone deacetylase activity for the medical therapy of conditions which predispose a person for the development of a disease, such as but not limited to cancer, inflammatory or metabolic diseases. Such conditions are linked to genetically inherited mutations of crucial genes which predispose a person with this condition to develop the disease phenotype. Thus, such compounds can be used for a suppressive therapeutic approach—the SUPPRESSION THERAPY—in order to inhibit or delay the onset or progression of the genetically predisposed disorder. Furthermore, a clinically used medicament can be manufactured for the SUPPRESSION THERAPY of such inherited predisposing conditions.

Abstract: Object matter of the invention is an optimized DNA sequence encoding the scFv(FRP5) antibody fragment. This novel sequence prevents the generation of the undesired by-product in the context of an scFv(FRP5)-ETA fusion protein, and possibly also other bacterially expressed scFv(FRP5)-containing fusion proteins. The DNA sequence of the scFv(FRP5) domain of scFv(FRP5)-ETA was modified by exchanging a distinct codon, thereby preventing an otherwise possible internal start of protein translation.

Abstract: This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(?O)— and —C(?O)NR1—; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, 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 HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psorias.

Abstract: The present invention relates generally to the treatment of diseases and disorders that are mediated by histone deacetylase (HDAC), for example, cancer, with Belinostat™ (also known as (E)-N-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide; PXD101; and PX 105684), and more particularly, to improvement treatments of such diseases (for example, cancers, for example, leukemias), which employ prolonged continuous infusion (e.g., prolonged continuous intravenous infusion) of Belinostat™.

Abstract: The invention relates to a method for determining whether a treatment of a disorder with an HDAC inhibitor is to be started/continued or not comprising determining the level of histone acetylation in the sample by use of an antibody capable of binding to acetylated histone, and classifying the disorder as to be treated with an HDAC inhibitor when the level of histone acetylation is significantly lower than that of a reference sample. The invention further relates to the diagnostic and prognostic use of specific antibodies and cell lines producing them.

Abstract: The present invention pertains to the general field of chemical synthesis, and more particularly to methods for the synthesis of certain hydroxamic acid compounds, and in particular, (E)-N-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide, also known as PXD101 and Belinostat®, comprising, for example, the steps of: (SAF) sulfonamide formation; (PURC) optional purification; (AAA) alkenyl-acid addition, comprising: either (i): the steps of, in order: (ACAEA) alkenyl-carboxylic acid ester addition; (PURE) optional purification; and (CAD) carboxylic acid deprotection; or (ii): the step of: (ACAA) alkenyl-carboxylic acid addition; (PURF) optional purification; (HAF) hydroxamic acid formation; and (PURG) optional purification.

Abstract: The present application discloses substituted 3-(4-hydroxyphenyl)-indolin-2-one compounds (oxindole compounds) of the formula and the use of such compounds for the preparation of a medicament for the treatment of cancer in a mammal, in particular in humans.

Abstract: This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C1 7alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the ?-position; and with the proviso that A is not benzimidazol-2-yl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

Abstract: This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C17alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the ?-position; and with the proviso that A is not benzimidazol-2-yl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof.

Abstract: The present invention relates to the use of an inhibitor of the formation of nicotinamide adenyl dinucleotide for the preparation of a medicament used in the treatment of inflammatory diseases such as rheumatoid arthritis and endotoxemia.