Abstract: Disclosed is a transdermally absorbable preparation, in which an adhesive agent produced by crosslinking at least one copolymer is contained in an adhesive layer and the aging period in the production of the adhesive layer can be shortened. The transdermally absorbable preparation comprises a support and an adhesive layer arranged on the support and containing an adhesive agent and a medicinal component. The transdermally absorbable preparation is characterized in that the adhesive agent comprises a resin mixture comprising 100 parts by mass of a specific acrylic copolymer (A) and 0.1 to 30 parts by mass of a specific acrylic copolymer (B) or 0.05 to 2 part(s) by mass of a polyamine compound, and the adhesive layer additionally contains an organic acid.

Abstract: The present invention involves compositions and methods for treating cancer using a mutant adenovirus comprising a polynucleotide encoding a therapeutic polypeptide that is targeted to cells with a mutant retinoblastoma pathway. The mutant adenovirus is able to kill the tumor cells without harming cells with a wild type retinoblastoma pathway.

Abstract: The invention is directed to novel pyrrolopyrimidine compounds of formula (1) wherein R1, R2y, R4, R8-R11, A and L are defined herein and to salts, including pharmaceutically acceptable salts thereof. The compounds of the present invention are CDK4/6 inhibitors and could be useful in the treatment of diseases and disorders mediated by CDK4/6, such as cancer, including mantle cell lymphoma, liposarcoma, non small cell lung cancer, melanoma, squamous cell esophageal cancer and breast cancer. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CDK4/6 activity and to the treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Abstract: A 10?-fluoro-vinca alkaloid compound or its pharmaceutically acceptable salt is disclosed, as are methods of its preparation and use. A disclosed 10?-fluoro-vinca alkaloid compound has better cytotoxic potency against leukemia and cancer cell lines, and is about 8-times more cytotoxic to a multiple drug resistant cancer cell line than is a parental 10?-unsubstituted vinca alkaloid.

Abstract: Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R1, R2, R4, R5, R6 and R7 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

Abstract: The present invention relates to ligand-therapeutic agent conjugate compounds, silicon linkers for the conjugate compounds, compositions, methods for making them, and methods for the treatment of cancer using the conjugate compounds. The silicon-based linkers described herein can be used to deliver desired therapeutic agents to particular cells or tissue types targeted by the ligand.

Abstract: The present invention relates to a prodrug, comprising a pharmaceutically and/or diagnostically active compound, and one or more bisphosphonate groups, to a process for producing such a prodrug, and to a pharmaceutical composition comprising said prodrug, to be used for the treatment of bone-related disorders such as bone cancer.

Abstract: The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent.

Abstract: Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations in a patient. The compounds described herein include conjugates of a plurality of cytotoxic drugs and vitamin receptor binding ligands. The plurality of drugs may be the same or different. Similarly, the vitamin receptor binding ligands may be the same or different. The conjugates also include a linker that is formed from one or more spacer linkers, heteroatom linkers, and releasable linkers.

Abstract: The invention is directed to novel pyrrolopyrimidine compounds of formula (I) wherein R1, R2Y, R4, R8-R11, A and L are defined herein and to salts, including pharmaceutically acceptable salts thereof. The compounds of the present invention are CDK4/6 inhibitors and could be useful in the treatment of diseases and disorders mediated by CDK4/6, such as cancer, including mantle cell lymphoma, liposarcoma, non small cell lung cancer, melanoma, squamous cell esophageal cancer and breast cancer. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CDK4/6 activity and to the treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Abstract: The present invention relates to anhydrous crystalline vinflunine salts obtained with 1 or 2 equivalents of a pharmaceutically acceptable mineral or organic acid [Acid] 1 or 2 in which [Acid] represents hydrobromic, sulfuric, lactic and fumaric acids for the group of water-soluble crystalline salts, and para-toluene sulfonic, benzoic, mandelic and para-hydroxy benzoic acids for the group of relatively insoluble crystalline salts.

Abstract: A 10?-fluoro-vinca alkaloid compound or its pharmaceutically acceptable salt is disclosed, as are methods of its preparation and use. A disclosed 10?-fluoro-vinca alkaloid compound has better cytotoxic potency against leukemia and cancer cell lines, and is about 8-times more cytotoxic to a multiple drug resistant cancer cell line than is a parental 10?-unsubstituted vinca alkaloid.

Abstract: The present invention relates to novel Death Domain Containing Receptor-4 (DR4) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR4 proteins. DR4 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR4 activity and methods for using DR4 polynucleotides and polypeptides. The invention also relates to the treatment of diseases associated with reduced or increased levels of apoptosis using antibodies specific for DR4, which may be agonists and/or antagonists of DR4 activity.

Abstract: Novel conjugates and immunogens derived from vincristine and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of vincristine in biological fluids.

Abstract: Provided are methods for treating a hematological malignancy comprising administering an effective amount of flubendazole alone or in combination with a vinca alkaloid. Also provided are compositions and kits comprising an effective amount of flubendazole and/or a vinca alkaloid for use in the methods of the disclosure.

Abstract: The invention provides vinblastine derivatives represented by the following formula 1 or their physiologically acceptable salts, their preparation, use and pharmaceutical compositions comprising the said derivatives. The said vinblastine derivatives show inhibiting activities against tumor cell lines and can be used as medicaments for treating malignant tumors.

Abstract: The present invention relates to compounds useful as inhibitors of protein kinases, particularly of JAK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: Novel conjugates and immunogens derived from vincristine and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of vincristine in biological fluids.

Abstract: The present invention relates to vinca alkaloid and analog N-oxides having activity for treating hyperproliferative disorders. Further, the invention relates to pharmaceutical compositions and methods of using vinca alkaloid and analog N-oxides, alone or in combination with one or more other active agents or treatments, to treat hyperproliferative disorders.

Abstract: The present invention relates to derivatives of vinca alkaloids. Pharmaceutical compositions containing these compounds as well as processes of preparation and treatment of various conditions are also disclosed.

Abstract: Antitumor combinations comprising a taxane and at least one antibiotic for treating neoplastic diseases are described.

Abstract: Antitumor combinations comprising a taxane and at least one therapeutically useful substance for treating neoplastic diseases are described.

Abstract: The present invention relates to compounds defined by formula (I) wherein the groups A, B, X, m, n and o are defined as in claim 1, possessing valuable pharmacological activity. Particularly the compounds are inhibitors of 11 ?-hydroxysteroid dehydrogenase (HSD) 1 and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme, such as metabolic diseases, in particular diabetes type 2, obesity and dyslipidemia.

Abstract: The present invention relates to synergistic combinations of the compound 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and vinca alkaloids, which have anti-tumour activity. Preferably, the present invention relates to synergistic combinations of the compound 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and vincristine. More particularly, the invention is concerned with the use of such combinations in the treatment of cancer and pharmaceutical compositions containing such combinations. The invention further provides for methods of preparing the combinations of the invention.

Abstract: The present invention relates to synergistic combinations of the compound 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) and a compound selected from anthracyclines and topisomerase II inhibitors, which have anti-tumor activity. Preferably, the present invention relates to synergistic combinations of the compound 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and a compound selected from etoposide, and doxorubicin. More particularly, the invention is concerned with the use of such combinations in the treatment of cancer and pharmaceutical compositions containing such combinations. The invention further provides for methods of preparing the combinations of the invention.

Abstract: Polyal-Drug conjugates comprising a variable rate-releasing linker are described along with methods of making such conjugates. Uses for such Polyal-Drug conjugates is also described.

Abstract: The present invention relates to 1-aza-bicycloalkyl derivatives of Formula (I) wherein the substituents are as defined in the specification and to processes for their production to pharmaceutical compositions comprising them and to their use in the manufacture of a medicament for the treatment and/or delay of progression of psychotic and nemodegenerative disorders.

Abstract: Chemotherapeutic conjugates of a peptide substrate to a phosphoramide chemotherapeutic agent in which a peptide substrate is covalently linked to the chemotherapeutic agent by a linker with an aminoarylmethyl or aminoheteroaryl moiety, wherein the linking of the peptide to the chemotherapeutic agent inhibits the cytotoxic activity of the chemotherapeutic agent, the peptide is a substrate for proteolytic cleavage by a tumor-specific enzyme; and the linker is capable of undergoing 1,6-elimination in vivo upon cleavage of the peptide substrate. Methods for synthesizing and methods of using the conjugates are also disclosed.

Abstract: The present invention relates to anhydrous crystalline vinflunine salts obtained with 1 or 2 equivalents of a pharmaceutically acceptable mineral or organic acid [Acid] 1 or 2 in which [Acid] represents hydrobromic, sulfuric, lactic and fumaric acids for the group of water-soluble crystalline salts, and para-toluene sulfonic, benzoic, mandelic and para-hydroxy benzoic acids for the group of relatively insoluble crystalline salts.

Abstract: The present invention relates to novel vinorelbine derivatives. Pharmaceutical compositions containing these compounds as well as processes of preparation and processes of use for treatment of various conditions are also disclosed.

Abstract: The present application describes deuterium-enriched vinflunine, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: Pyrrolopyrimidine derivatives of the formula I in which R3, R4, R5, R6 and X are as defined in claim 1, act as phosphodiesterase VII inhibitors and can be employed for the treatment of osteoporosis, tumours, cachexia, atherosclerosis, rheumatoid arthritis, multiple sclerosis, diabetes mellitus, inflammatory processes, allergies, asthma, autoimmune diseases, myocardial diseases and AIDS.

Abstract: The present invention relates to vinca alkaloid and analog N-oxides having activity for treating hyperproliferative disorders. Further, the invention relates to pharmaceutical compositions and methods of using vinca alkaloid and analog N-oxides, alone or in combination with one or more other active agents or treatments, to treat hyperproliferative disorders.

Abstract: An intermediate for vinblastine synthesis represented by general formula A. general formula A. (in the formula, R1, R2, R3 and R4 are the group selected independently from the group consisting of H, lower alkyl group, lower alkoxy group, halogen, lower perfluoroalkyl group, lower alkylthio group, hydroxy group, amino group, mono- or di-alkyl or acylamino group, lower alkyl or arylsulfonyloxy group. R5 is H, or a lower alkyl group or a substituted or non-substituted aryl group, R6 is an alkyl group of carbon number 4 or less, R7 is a substituted or non-substituted aryl group, R8 is a substituted or non-substituted aryl group or lower alkyl group and R9 is an acyl group or trialkylsilyl group.

Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.

Abstract: The present invention relates to derivatives of vinca alkaloids. Pharmaceutical compositions containing these compounds as well as processes of preparation and treatment of various conditions are also disclosed.

Abstract: The present invention relates to novel vinorelbine derivatives. Pharmaceutical compositions containing these compounds as well as processes of preparation and processes of use for treatment of various conditions are also disclosed.

Abstract: Disclosed are compounds of general formula (I) that function as prodrugs, thereby increasing bioavailabilities of the linked therapeutic agents, wherein the LINKER is (i) substituted or unsubstituted alkyl, (ii) substituted or unsubstituted alkenyl, (iii) substituted or unsubstituted alkanoyl, (iv) substituted or unsubstituted alkenoyl wherein the double bond is cis, and (v) (ortho or para) carbonyl-substituted aryl; and wherein the subtituent is each an independent group or linked together thereby forming a ring; and wherein X is one or more substituted or unsubstituted group containing one or more O, N, or S atom and wherein the substituent is each an independent group or linked together thereby forming a ring; and wherein the therapeutic agent is an alcohol-containing water-insoluble steroids or another alcohol containing compounds and methods to prepare such compounds.

Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.

Abstract: The present invention provides a fluorescent substance which is represented by a formula: A-B-C

Abstract: This invention provides compounds of formula I and pharmaceutically-acceptable salts thereof, where the substituents are defined in the specification, which are growth hormone secretogogues useful for treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength , mobility, maintenance of skin thickness, metabolic homeostatis or renal homeostasis. Compounds of formula I in combination with: a bisphosphonate such as alendronate; estrogen, estrogens, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions thereof are useful in treating osteoporosis.

Abstract: The invention concerns a novel method for preparing vinca-alkaloids by reacting a catharantine-type product and a vindoline-type product, characterized in that it consists in selecting the reaction conditions such that the product is oxidized.

Abstract: The present invention provides methods and compositions for enhancing the activity of various therapeutic agents that induce apoptosis by modulating the apoptosis-inhibiting effects of the expression products of mutant epidermal growth factor receptor (EGFR) genes. Methods and compositions of particular use in the treatment of cancers, such as glioma, that express such a mutant EGFR gene are provided.

Abstract: The present invention relates to compounds of formulas (IA), (IB), and (IC): the preparation thereof, pharmaceutical formulations thereof, and their use in medicine as allosteric adenosine receptor modulators for uses including protection against hypoxia and ischemia induced injury and treatment of adenosine-sensitive cardiac arrhythmias.

Abstract: The invention concerns novel halogenated derivatives of the vinblastine and vinorelbine family, corresponding to general formula (I) and their therapeutically acceptable salts. The invention also concerns the application of these compounds in therapy and their method of preparation. The invention further concerns a novel method for preparing vinflunine or 20',20'-difluoro-3',4'-dihydrovinorelbine, of formula (a).

Abstract: Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by a diamine linker between the oligopeptide and vinblastine. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Abstract: The present invention is particularly directed to the use of a derivative of vinblastine, 3',4'-anhydrovinblastine (AHVB), which differs from vinblastine in that it possesses a double bond at the 3',4' position of the caranthine nucleus rather than the hydroxyl group that is present in the parent structure, as an antineoplastic agent in the therapeutic treatment of cancer. Specifically, the treatment of lymphoma with 3',4'-anhydrovinblastine is disclosed.

Abstract: Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Abstract: The invention provides a method of producing a culture of polycystic kidney cells which form cysts in vitro. A cell culture of polycystic kidney cells is also provided. A method for screening an agent in vitro to determine the effectiveness of the agent in treating polycystic kidney disease is disclosed. Further, a method of treating a mammal having polycystic kidney disease by administering a pharmaceutical composition is provided.

Abstract: The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.