Abstract: The present invention relates to a novel class of alkylating agents comprising a thieno-indole moiety linked to a DNA-binding moiety, which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds or the pharmaceutical composition containing them. The invention also relates to the use of this novel class of alkylating agents in the preparation of conjugates.

Abstract: Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease. Various pro-inflammatory mediators are elevated in a model of COPD that can be used predict the presence of COPD and/or subtypes of COPD in human patients. Profiles of these mediators can also predict the responsiveness of some patients to certain therapies, including thromboxane receptor antagonist treatment. Methods are provided for diagnosing a subject as a pulmonary disease candidate that include determining leukocyte expression in the subject of at least one pro-inflammatory mediator and identifying the subject as a pulmonary disease candidate when leukocyte expression in the subject of the pro-inflammatory mediator is increased compared to leukocyte expression of the pro-inflammatory mediator in a healthy individual. The pulmonary disease candidate can also be treated by administering a therapeutically effective amount of a thromboxane receptor antagonist.

Abstract: The present invention relates to the treatment of breast cancer which is estrogen receptor positive (ER+) and/or human epidermal growth factor receptor 2 positive (HER2) and/or progesterone receptor positive (PR) and/or facilitates chromatin transcription positive (FACT+) with a curaxin, including curaxin 137. The present invention also pertains to a method of identifying a subject who has a breast cancer tumor and is likely to respond to treatment with a curaxin.

Abstract: Radioprotector compounds including 3,3?-diindolylmethane (DIM) analogs, are provided. Further provided are methods for their use in reducing or preventing radiation damage, killing a tumor cell and protecting a non-tumor cell, and treating cancer.

Abstract: One aspect of the invention provides a method for treating a clinical condition associated with inappropriate or abnormal activation of HER3/ErbB3. In some embodiments, the method of the invention inhibits interaction between MTK1 and actin.

Abstract: Allergies and immune system disorders (e.g. autoimmune diseases) are treated by administration of an agent that blocks activation of the kainic acid receptor (KAR) in B cells. The agents include antagonists and weakly activating agonists.

Abstract: The present invention relates to novel strigolactam derivatives of formula (I) to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants and/or promoting the germination of seeds.

Abstract: The present invention relates to methods, compounds, and compositions for inhibiting angiogenesis. More particularly, the present invention relates to methods, compounds, and compositions for inhibiting VEGF production.

Abstract: This invention relates to novel analogs of the DNA-binding alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Abstract: Compositions and methods for the treatment and control of various conditions in an animal which comprises administering to said animal an effective amount of a immediate release composition of about 0.5% to 50% wt/wt of active ingredient together with excipients to a total of about 100%, wherein said composition dissolves in a relatively short period of time, e.g., 75 seconds or less, 5 seconds or less, or 3 seconds or less, upon administration to said animal.

Abstract: The disclosure provides methods of treating glioblastoma, methods of screening for compounds that treat glioblastoma, and pharmaceutical compositions useful in the treatment of glioblastoma.

Abstract: The present invention generally relates to the transdermal delivery of various compounds. In some aspects, transdermal delivery may be facilitated by the use of a hostile biophysical environment. One set of embodiments provides a composition for topical delivery comprising ergopeptines, triptans, and other compounds, including salts and derivatives of these, and optionally, a hostile biophysical environment and/or a nitric oxide donor. In some cases, the composition may be stabilized using a combination of a stabilization polymer (such as xanthan gum, KELTROL® BT and/or KELTROL® RD), propylene glycol, and a polysorbate surfactant such as Polysorbate 20, which combination unexpectedly provides temperature stability to the composition, e.g., at elevated temperatures such as at least 40° C. (at least about 104° F.), as compared to compositions lacking one or more of these.

Abstract: The present invention relates to a method for labeling or targeting cells whose plasma membrane has lost integrity, such as dead cells, such as for discriminating between live cells and cells whose plasma membrane has lost integrity; to an embodiment of the method for determining one or more values of one or more parameters of cells of a biological sample; to use of the method in an assay for screening drugs for therapy such as cancer therapy; to use of the method to monitor and/or determine the effectiveness of a therapy; to an assay kit; to a complex; to the complex for use as a medicament; to the complex for use in treatment of cancer(s) and/or plaque(s) and/or regeneration and/or supporting the immune system; and, to a dead cell.

Abstract: The invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

Abstract: Active compound combinations are disclosed which comprise (A) a dithiino-tetracarboximide of formula (I) and a further insecticidally active compound (B). Methods for controlling animal pests such as insects and/or unwanted acarids and for curatively or preventively controlling the phytopathogenic fungi of plants or crops are also disclosed as well as the use of a composition according to the invention for the treatment of seed, to a method for protecting a seed and to the treated seed.

Abstract: An object of the present invention is to provide a drug delivery system capable of sustainedly releasing a drug noninvasively at any given point in time. The present invention relates to a liposome complex comprising a liposome membrane-constituting substance bonded to a light-absorbing compound having an absorption wavelength in the near-infrared region, selected from the group consisting of indocyanine green dyes, phthalocyanine dyes, squarylium dyes, croconium dyes, and diimmonium dyes.

Abstract: Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

Abstract: Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Abstract: The present invention relates to articles and methods of treating vascular conditions with a thixotropic, turbid, bioactive agent-containing gel material capable of being essentially removed from an implantation site upon re-establishment of fluid flow at the implantation site.

Abstract: The present invention relates to compositions, in particular within a fungicide composition, which comprises (A) a dithiino-tetracarboximide of formula (I) and a further fungicidally active compound (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and to the treated seed.

Abstract: A method for treating an abnormal polyglutamine-mediated disease is disclosed, wherein indole and an indole-based compound contained in a pharmaceutical composition used in the method of the present invention can reduce the polyglutamine aggregation through decreasing reactive oxygen species production and increasing the activity of chaperone and autophagy.

Abstract: The present invention relates to processes and intermediates useful in the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia) and salts thereof, an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development and atherosclerosis).

Abstract: The present invention relates to compositions, in particular within a fungicide composition, which comprises (A) a dithiino-tetracarboximide of formula (I) and a further fungicidally active compound (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and to the treated seed.

Abstract: The present invention relates to compositions, in particular within a fungicide composition, which comprises (A) a dithiino-tetracarboximide of formula (I) and a further fungicidally active compound (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and to the treated seed.

Abstract: The present invention relates to compositions, in particular within a fungicide composition, which comprises (A) a dithiino-tetracarboximide of formula (I) and a further fungicidally active compound (B). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and to the treated seed.

Abstract: The invention relates to a family of compounds that comprise fluorescent cyanine dyes. The compounds are near infrared absorbing heptamethine cyanine dyes with a 4,4-disubstituted cyclohexyl ring as part of the polymethine chromophore. The compounds are generally hydrophilic and can be chemically linked to biomolecules, such as proteins, nucleic acids, and therapeutic small molecules. The compounds can be used for imaging in a variety of medical, biological and diagnostic applications.

Abstract: A compound of formula (I) useful for the treatment or prevention of hepatitis C viral infection, (Formula (I)) wherein: X1 and X2 are each independently CRB or N; RB is H, (C1-6)alkyl, (C1-6)haloalkyl, halo.

Abstract: This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.

Abstract: A stable solid oral pharmaceutical composition comprising carvedilol or a pharmaceutically acceptable salt thereof, which is packed using a suitable packaging material along with a desiccant. A process for manufacturing a stable solid oral dosage form containing carvedilol or a pharmaceutically acceptable salt thereof, which is packed in the packaging configuration comprising moisture permeation inhibitory packaging. A method of preparing a stable solid oral pharmaceutical dosage form, said method comprising, encasing a pharmaceutical dosage form comprising carvedilol or pharmaceutically acceptable salt thereof in a container comprising a desiccant. A pharmaceutical kit comprising a container impervious to moisture, wherein said container comprises a desiccant; and a solid oral pharmaceutical dosage form comprising carvedilol or a pharmaceutically acceptable salt thereof, wherein said pharmaceutical dosage form is encased in said container.

Abstract: The invention relates to injectable pharmaceutical compositions, methods of use and formulation, wherein the compositions comprise: one or more water soluble complexes, each complex comprising a cyclodextrin or a cyclodextrin derivative and a hydrophobic drug; at least one preservative; and at least one co-solvent. The compositions are effectively preserved in accordance with the European Pharmacopoeia 2011 Test for Efficacy of Antimicrobial Preservation, satisfying at least the B criteria as it applies to parenterals, and the United States Pharmacopeia 2011 Guidelines for Antimicrobial Effectiveness Testing, satisfying the criteria for Category 1 (injectable) products.

Abstract: The present invention relates to novel pharmaceutical combinations with synergistic action of diacerein or a pharmaceutically acceptable salt of diacerein and non-steroidal inflammatory drugs, having analgesic, anti-inflammatory, antipyretic, and osteoarthritis-treating activities.

Abstract: Tricyclic compounds, compositions and uses thereof in the treatment of at least one disease, disorder or condition such as for example obesity, overweight, abnormal fat-distribution and any conditions or disease associated therewith.

Abstract: The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors (1) at least one EP4 receptor antagonist (2), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain at least one EP4 receptor antagonist (2), in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partly saturated or saturated heterocyclic group or an optionally substituted, mono- or bicyclic heteroaryl and wherein R1 and R2 have the meanings given in claim 1, the preparation thereof and the use thereof for the treatment of respiratory complaints.

Abstract: This technology relates generally to compounds and methods for stimulating neurogenesis (e.g., post-natal neurogenesis, including post-natal hippocampal and hypothalamic neurogenesis) and/or protecting neuronal cell from cell death. Various compounds are disclosed herein. In vivo activity tests suggest that these compounds may have therapeutic benefits in neuropsychiatric and/or neurodegenerative diseases such as schizophrenia, major depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury, post-traumatic stress disorder, Parkinson's disease, Alzheimer's disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, physiological weight loss associated with various conditions, as well as cognitive decline associated with normal aging, chemotherapy, and the like.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present invention relates to methods for the protection of harvested fruits, cutflowers or vegetables against decay caused by certain storage diseases or disorders expressed in storage conditions, which fruits, cutflowers or vegetables have been treated pre-harvest with dithiino-tetracarboximides for formula (I). In particular the invention relates to the application of dithiino-tetracarboximides of formula (I) before harvest to protect harvested fruit, cutflowers or vegetables against phytopathogenic fungi.

Abstract: The present invention provides methods to reduce or inhibit weight gain by administering inhibitors of the SirT1 protein to a subject. Methods to identify such inhibitors are also disclosed.

Abstract: This disclosure relates to compounds of formula I: wherein R1, R2, R3, R4, X and Y have the meanings denoted in the disclosure. The compounds of formula I have antithrombotic activity and in particular inhibit the protease-activated receptor 1 (PAR1). The disclosure further relates to a method for producing the compound of formula I and to the use thereof as a pharmaceutical product.

Abstract: In one aspect, the invention relates to substituted 2-(1H-indol-3-yl)ethanol analogs and substituted 3,3a,8,8a-tetrahydro-2H-furo[2,3-b]indole analogs, derivatives thereof, and related compounds, which are useful as inhibitors of IL-6 mediated activation of the Jak2/STAT3 pathway; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a IL6 dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention relates to a novel hydroxamate derivatives, more specifically, to novel hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC), isomers thereof, pharmaceutically acceptable salts thereof, hydrates or solvates thereof, use for preparing pharmaceutical compositions, pharmaceutical compositions comprising the same, treatment method using said composition, and a preparing method of novel hydroxamate derivatives. The novel selective hydroxamate derivatives having inhibitory activity against Histone Deacetylase (HDAC) compositions can be used for treatment of inflammatory disease, rheumatoid arthritis, or degenerative disease.

Abstract: A method for treating migraines is disclosed. The method utilizes a rapid drug delivery system which prevents deactivation or degradation of the active agent, including small molecules and peptides being administered to a patient in need of treatment. In particular, the drug delivery system is designed for inhalation for delivery of drugs to the pulmonary circulation in a rapid and therapeutically effective manner.

Abstract: The present invention relates to the use of novel and of known dithiine-tetracarboximides for controlling phytopathogenic fungi, and to methods of controlling phytopathogenic fungi in plant protection, and to plant protection compositions comprising these dithiine-tetracarboximides.

Abstract: The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, malaria, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; killing or inhibiting the growth of a Plasmodium species; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative.

Abstract: The present invention is directed to certain hydroxamate derivatives that are useful in the treatment of hepatitis C. These compounds are also inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

Abstract: Compounds of the general structural formula (I) and (II) and use of the compounds and salts and hydrates thereof, as therapeutic agents are disclosed. Treatable diseases and conditions include cancers, inflammatory diseases and conditions, and immunodeficiency diseases. (I), (II).

Abstract: The present invention relates to processes and intermediates useful in the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia) and salts thereof, an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development and atherosclerosis).

Abstract: The present application relates to aryl- and heteroaryl-fused decahydropyrroloazepine, octahydrooxepinopyrrole, octahydropyrrolothiazepine dioxide, decahydrocyclohepta[c]pyrrole, and octahydrocyclohepta[c]pyrrole derivatives of formula (I) wherein R1, R2, R3, R4, R5, A, Y1, Y2, and Y3 are as defined in the specification. The present application also relates to compositions comprising such compounds, processes for making such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

Abstract: In one aspect, the invention provides compounds of Formula I, and salts, hydrates and isomers thereof. In another aspect, the invention provides a method of promoting bone formation in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of Formula I, Formula II, or Formula III. The present invention also provides orthopedic and periodontal devices, as well as methods for the treatment of renal disease and cancer, using a compound of Formula I, Formula II, or Formula III.

Abstract: There are provided inter alia methods and compounds useful for decreasing neovascularization (e.g., choroidal neovascularization) in a subject in need thereof.

Abstract: Cyanine dyes having optional sulfonic acid substituents on the aromatic nucleus have been developed for use as contrast agents for assisting in surgery and diagnosis, especially for simplifying the surgical removal of basal membranes of the eye, such as the internal limiting membrane (ILM), and for dyeing the lens capsule.