Abstract: The present invention is directed to antisense oligomeric compounds that may be used in the treatment Pompe disease as well as method for modulating the splicing of the GAA gene and method to treat Pompe disease. Also pharmaceutical compositions comprising the antisense oligomeric compounds are part of the invention.

Abstract: The application describes Hydrogen Sulphide (H2S), or a (H2S) generating compound or compound capable of stimulating H2S production in a pregnant subject, for use in the treatment of pre-eclampsia (PE) or fetal growth restriction.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Abstract: The present invention is directed to antisense oligomeric compounds that may be used in the treatment Pompe disease as well as method for modulating the splicing of the GAA gene and method to treat Pompe disease. Also pharmaceutical compositions comprising the antisense oligomeric compounds are part of the invention.

Abstract: The application describes Hydrogen Sulphide (H2S), or a (H2S) generating compound or compound capable of stimulating H2S production in a pregnant subject, for use in the treatment of pre-eclampsia (PE) or fetal growth restriction.

Abstract: A method of alleviating or treating symptoms of cancer and/or effects of chemotherapy or of kinase inhibitors includes a step of identifying a subject having cancer. A reduced caloric diet is administered to the subject for a first time period, the reduced caloric diet providing at most 1000 kcal per day. A kinase inhibitor is administered to the subject.

Abstract: The present invention provides dicyclohexylamine salt of fosaprepitant (fosaprepitant DCHA), a process for preparing fosaprepitant DCHA, and a use of fosaprepitant DCHA in the preparation of pharmaceutically acceptable fosaprepitant dimeglumine with high purity. Fosaprepitant dimeglumine is prepared by treating fosaprepitant DCHA with an acid to form fosaprepitant, followed by adding N-methyl-D-glucamine to fosaprepitant.

Abstract: Certain embodiments are directed to methods of treating respiratory infection by administering an H2S donor.

Abstract: Certain embodiments are directed to methods of treating respiratory infection by administering an H2S donor.

Abstract: The present invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating cancer (e.g., hematological malignancies in humans). A variety of biomarker chromosomal number alterations (CNAs) and biomarkers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the biomarker CNAs and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers comprised within the CNAs is associated with cancer status.

Abstract: The present application discloses compounds of formula (I) wherein X is ?O, ?S, ?NH, ?NOH and ?NO-Me; A is —C(?O)—, —S(?O)2—, —C(?S)— and P(?O)(R5)—; B is, —O—, —(CH2)3-6—, and O—(CH2)2-5—; D is, —O—, —CR7R8— and —NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

Abstract: The present application discloses compounds of formula (I) wherein X is ?O, ?S, ?NH, ?NOH and ?NO-Me; A is —C(?O)—, —S(?O)2—, —C(?S)— and P(?O)(R5)—; B is, —O—, —(CH2)3-6—, and O—(CH2)2-5—; D is, —O—, —CR7R8— and —NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt. sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

Abstract: The invention is directed to a method of administering hydrogen sulfide (H2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.

Abstract: Novel bisphosphonate cyclic acetal compounds are disclosed, as well as methods of preparing the compounds, pharmaceutical compositions including the compounds, and administration of the compounds in methods of treating bone metabolism disorders, such as abnormal calcium and phosphate metabolism.

Abstract: This disclosure relates to novel compounds containing an H2S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including cancers. Therapeutic potency of these compounds is significantly higher than NSAIDs containing a H2S-releasing moiety alone (HS-NSAIDs) and NSAID containing a NO-releasing moiety alone (NO-NSAIDs). The compounds, in addition, exhibit reduced side effect, e.g., reduced stomach ulcers, upon administration.

Abstract: Oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3? and/or 5?-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Abstract: The present invention provides a method of hydroxylating or oxidizing a compound of interest in a subject (e.g., a cytotoxic oxazaphosphorine prodrug), by administering the compound of interest to the subject; and concurrently administering the subject a metalloporphyrin in an amount effective to hydroxylate or oxidize the compound of interest in the subject.

Abstract: The present invention relates to methods of treating a cancer and in particular, a B-cell derived cancer, using a lymphocytotoxic but hematopoeitic cell sparing high-dose pulsed amount of an oxazaphosphorine drug in combination with immune therapeutics such as, for example, an autologous idiotypic vaccine and monoclonal antibodies that selectively bind B-cell specific antigens.

Abstract: The present invention generally relates to a process for the preparation of fosaprepitant dimeglumine intermediate and its use in the preparation of fosaprepitant dimeglumine; to a neutral form of fosaprepitant in a solid state and processes for the preparation thereof; and to a stable amorphous fosaprepitant dimeglumine, having a stability at temperatures of about 2° C. to about 8° C. and at a relative humidity below at least 60%; and a process for the preparation thereof.

Abstract: Described are stable liquid formulations of nitrogen mustards. The nitrogen mustard includes mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, uramustine, thiotepa and combinations thereof. The formulation includes a non-aqueous liquid having at least a first solvent either individually or in combination with one or more additional solvents. The formulation further includes an antioxidant, an organic acid, and a source of chloride ions.

Abstract: The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including a taxane or a taxane derivative. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including a taxane or a taxane derivative and administering the therapy in subjects when it is found that a taxane or a taxane derivative is likely to be effective.

Abstract: The invention is directed to a method of administering hydrogen sulfide (H2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to compositions and methods for treating an animal diagnosed with Glioblastoma multiforme (GBM).

Abstract: The present invention relates to compounds of Formula (I): and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds inhibit Bcl-2 and/or Bcl-XL activities and may be used for the treatment of cancer.

Abstract: The invention is directed to a method of administering hydrogen sulfide (H2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to novel phosphorous derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.

Abstract: Pharmaceutical compositions comprise a first compound of Formula I or a physiologically acceptable salt thereof, and a cyto-protective amount of a manganese chelate of N,N?-dipyridoxyl ethylenedianiine-N,N?-diacetic acid (MnPLED): wherein R1, R2, R3, R4 and X are defined in the specification.

Abstract: The present invention provides a method of hydroxylating or oxidizing a compound of interest in a subject (e.g., a cytotoxic oxazaphosphorine prodrug), by administering the compound of interest to the subject; and concurrently administering the subject a metalloporphyrin in an amount effective to hydroxylate or oxidize the compound of interest in the subject.

Abstract: The present invention is to provide means to treat breast cancer and/or mastitis by topically administering a non-steroidal antiinflammatory analgetic agent and/or an anticancer agent and allowing them efficiently to arrive into the mammary gland. The present invention provides an iontophoretic preparation for treating breast cancer and/or mastitis which contains a non-steroidal antiinflammatory analgetic agent and/or an anticancer agent as an active ingredient and has a donor to be applied on a nipple part for topical administration of the active ingredient from the nipple part to the mammary gland by application of electric potential.

Abstract: This invention relates to methods of inducing differential stress resistance in a subject with cancer by starving the subject for a short term, administering a cell growth inhibitor to the subject, or reducing the caloric or glucose intake by the subject. The induced differential stress resistance results in improved resistance to cytotoxicity in normal cells, which, in turn, reduces cytotoxic side-effects due to chemotherapy, as well as improved effectiveness of chemotherapeutic agents.

Abstract: One aspect of the present invention relates to a method of controlling axon or dendrite development in a neuronal cell population. This method involves providing a neuronal cell population and contacting the neuronal cell population with a modulator of R-type Ca2+ channel expression or activity in controlling the neuronal cell population to induce either axon or dendrite development. Another aspect of the present invention relates to a method of treating neuronal injury in a subject. This method involves selecting a subject with neuronal injury mediated by R-type Ca2+ channel expression or activity and administering to the selected subject an inhibitor of R-type Ca2+ channel expression or activity to induce neuronal axon development under conditions effective to treat the neuronal injury in the subject. Yet another aspect of the present invention relates to a method of screening for agents that modulate R-type Ca2+ channel expression or activity.

Abstract: The invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of formula I: wherein the variables are as defined herein.

Abstract: Disclosed are methods of increasing the chemosensitivity of normal and/or chemoresistant tumor or cancer cells using thyroid hormone analogs and/or nanoparticulate or polymeric forms thereof. Also disclosed are methods of increasing radiosensitivity of normal and/or radioresistant tumor or cancer cells using thyroid hormone analogs and/or nanoparticulate or polymeric forms thereof.

Abstract: Novel bisphosphonate cyclic acetal compounds are disclosed, as well as methods of preparing the compounds, pharmaceutical compositions including the compounds, and administration of the compounds in methods of treating bone metabolism disorders, such as abnormal calcium and phosphate metabolism.

Abstract: The present disclosure in general relates to methods, systems, and apparatus for identifying modification of a medicinal compound exposed to a sample for use in determining which treatment to provide to a subject in need thereof.

Abstract: The present invention provides compounds of Formula I: and related compounds as further described herein, and pharmaceutical compositions comprising these compounds. The invention further provides methods to use these compounds and compositions for treating disorders associated with undesired levels of Pim kinase activity, including cancers and autoimmune disorders.

Abstract: The present application discloses novel squaric acid derivatives of the formula A: from —C(?O)—, —S(?O)2—, —C(?S)— and —P(?O)(R5)—; B: -, —O—, —NR6— and —C(?O)—NR6—; D: -, —O—, —CR7R8— and —NR9; m=0-12; n=0-12; m+n=1-20; p=0-2; R1: heteroaryl, aryl; R2: H, C1-12-alkyl, C3-12-cycloalkyl, —[CH2CH2O]1-10—(C1-6-alkyl), C1-12-alkenyl, aryl, heterocyclyl, heteroaryl; R3: C1-12-alkyl, C3-12-cycloalkyl, —[CH2CH2O]1-10—(C1-6-alkyl), C1-12-alkenyl, aryl, heterocyclyl, heteroaryl; or R2 and R3: N-containing heterocyclic/heteroaromatic ring; R4 and R4*: H, C1-12-alkyl, C1-12-alkenyl; and pharmaceutically acceptable salts and prodrugs thereof, and their use in the treatment of diseases/conditions caused by an elevated level of NAMPRT (inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and CPOD, osteoarthritis, osteoporosis and fibrotic diseases; dermatosis; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankyl

Abstract: The present disclosure relates to (thio)morpholine derivatives of the formula (I) wherein R1 is selected from cyano, (2-4C)alkynyl, (1-4C)alkyl, (3-6C)cycloalkyl, (4-6C)cycloalkenyl, (6-8C)bicycloalkyl, (8-10C)bicyclic group, each optionally substituted with (1-4C)alkyl, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (2-4C)alkynyl, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino, —SO2-(1-4C)alkyl, —CO-(1-4C)alkyl, —CO—O-(1-4C)alkyl, —NH—CO-(1-4C)alkyl and (3-6C)cycloalkyl, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl, monocyclic heterocycle optionally substituted with halogen, (1-4C)alkyl or with phenyl optionally substituted with (1-4C)alkyl, and bicyclic heterocycle optionally substituted with (1-4C)alkyl; A is selected from —

Abstract: The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

Abstract: The present invention relates to novel phosphorous derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.

Abstract: Provided herein are methods of treating lysosomal storage disease, for instance Pompe disease, through inhibition of autophagy. Optionally, treatment is administered as an adjunct to enzyme replacement therapy (ERT).

Abstract: The present invention includes novel compounds and pharmaceutically acceptable formulations of said compounds which exhibit antibiotic activity against microorganisms bearing a guanine riboswitch that controls the expression of the guaA gene, including organisms which are resistant to certain antibiotic families, and which are useful as antibacterial agents for treatment or prophylaxis of bacterial infections in animals or in humans, in particular but not limited to infections of the mammary gland, or their use as antiseptics, agents for sterilization or disinfection.

Abstract: The present invention provides a method of hydroxylating or oxidizing a compound of interest in a subject (e.g., a cytotoxic oxazaphosphorine prodrug), by administering the compound of interest to the subject; and concurrently administering the subject a metalloporphyrin in an amount effective to hydroxylate or oxidize the compound of interest in the subject.

Abstract: The present invention provides methods for improving the pharmacokinetics of protease inhibitors and protease inhibitor precursors and pharmaceutical composition comprising protease inhibitors or protease inhibitor precursors of formula I and a cytochrome P450 monooxigenase inhibitor; when the compound of formula I comprises an amino group, pharmaceutically acceptable ammonium salts thereof, wherein R1 may be, for example, (HO)2P(O)—, (NaO)2P(O)—, alkyl-CO— or cycloalkyl-CO—, wherein X may be, for example, F, Cl, and Br, and wherein R2 and R3 are as defined herein.

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

Abstract: The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

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

Abstract: The present application discloses compounds of formula (I) wherein X is ?O, ?S, ?NH, ?NOH and ?NO-Me; A is —C(?O)—, —S(?O)2—, —C(?S)— and P(?O)(R5)—; B is, —O—, —(CH2)3-6—, and O—(CH2)2-5—; D is, —O—, —CR7R8— and —NR9; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; R1 is opt.sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimers disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia.

Abstract: The invention is related to phosphorus substituted compounds with antiviral activity, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.