Abstract: The present invention is directed to 6-(1H-imidazo-1-yl)-2-aryl and 2-heteroaryl quinazoline and quinolines derivatives, compounds of formula (I), their pharmaceutical acceptable salts and solvates and corresponding pharmaceutical compositions, that acts as Monoamine Oxidase (MAO) inhibitors and Imidazoline Receptor ligands: wherein: X is independently selected from —CH group or a nitrogen atom (—N), W is independently selected from an aryl group, an heteroaryl group, or a benzocondensed heteroaryl group such as 1,3-benzodioxole, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, 2,3-dihydrobenzothiophene, indole, 2,3-dihydroindole, benzimidazole, benzoxazole, benzothiazole, 2H-3,4-dihydrobenzopyran, [1,4]-benzodioxine, 2,3-dihydro-[1,4]-benzodioxine (1,4-benzodioxan). R1 is independently selected from hydrogen (—H), C1-C4 alkyl, hydroxymethyl (—CH2OH), aminomethyl (—CH2NH2), alkylaminomethyl [CH2NH(R2)], or di-alkylaminomethyl [CH2N(R2)2], trifluoromethyl (—CF3).

Abstract: Hydrophobic weak base compounds such as hydrophobic weak base chemotherapeutic agents (which are not an anthracycline) for use in the treatment of medical conditions such as proliferative disease or disorder in a subject, in combination with illumination of a region in a body of the subject which is characterized by the presence of proliferating cells, are disclosed. The hydrophobic weak base compound and a wavelength of illumination are selected such that the hydrophobic weak base compound acts as a therapeutically effective photosensitizer when exposed to the illumination.

Abstract: Disclosed are novel camptothecin derivatives having anti-tumor activity (the basic structure thereof is as shown in the figure) and compositions of such compounds and use thereof. The compounds according to the present invention exhibit very good water solubility and stability, show good selectivity among drugs of the same category, and have a very high therapeutic index. Such compounds are promising as therapeutic agents for treating tumors.

Abstract: In the present invention there is provided a pharmaceutical composition in a solid dosage form suitable or oral administration, the composition comprising bendamustine or a pharmaceutically acceptable ester, salt or solvate thereof as an active ingredient, and at least one pharmaceutically acceptable excipient, which is a pharmaceutically acceptable saccharide selected from the group consisting of one or more of a monosaccharide, a disaccharide, an oligosaccharide, a cyclic oligosaccharide, a polysaccharide and a saccharide alcohol, wherein the ratio by weight of the active ingredient to the saccharide excipient(s) is in the range of 1:1-5.

Abstract: The present invention relates to pharmaceutical formulations that increase the solubility and bioavailability of indibulin, such as a spray-dried solid dispersion of indibulin with at least one matrix polymer. The invention further provides dosage formulations comprising the dispersion and processes for making the dispersion. The present invention also discloses a method of treating immune system based disorders, hyper-proliferative disorders, angiogenesis, malignancies, and neoplasms with the indibulin formulations disclosed herein.

Abstract: Heterobifunctional polymeric prodrug platforms for delivering biologically active compounds, including proteins, monoclonal antibodies and the like are disclosed. One preferred compound is Methods of making and using the compounds and conjugates described herein are also provided.

Abstract: This invention concerns methods of identifying treatments for treating various disorders and related computer products and systems. Also disclosed are methods for treating cellular proliferative disorders and use of compounds identified for such treatment.

Abstract: The present invention provides a method for diagnosing KRAS mutations in colorectal cancers by measuring the level of OLFM4. In another aspect, the present invention relates a method of predicting the responds to a chemotherapeutic agent of a subject suffering from a colorectal cancer: according to the present invention, the by determining the OLFM4 levels. According to the present invention, the response can be predicted by determining the OLFM4 levels. This result in turn permits the design or the adaptation of a treatment of the said subject with the said chemotherapeutic agent.

Abstract: The present invention provides a compound of formula (A): as described herein, and pharmaceutically acceptable salts, enantiomers, rotamers, tautomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by PIM kinase using the compounds of Formula I, and pharmaceutical compositions comprising such compounds.

Abstract: The present disclosure generally relates to methods of making nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol.

Abstract: The present invention relates to a compound comprising an imine bond as an acid-labile trigger group, the use of such an imine bond as an acid-labile trigger group, a process of cleaving the imine bond in said compound, and a pharmaceutical composition comprising said compound.

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

Abstract: The present invention provides methods and compositions for inducing expression of Ube3a in a cell by contacting the cell with a topoisomerase inhibitor. Particular embodiments include a method of treating a genomic imprinting disorder, such as Angelman syndrome, in a subject by administering to the subject an effective amount of a topoisomerase inhibitor.

Abstract: The present invention relates to the treatment or prevention of mucocutaneous herpes simplex virus diseases using prolonged release mucoadhesive buccal tablets comprising an acyclic guanosine antiviral agent. These tablets are particularly suitable for the treatment or prevention of orofacial herpes.

Abstract: The invention relates to methods for screening and identification of compounds and compositions that are useful in the treatment of neurological disorders, for example, of polyQ tract expansion diseases, such as Huntington's Disease. The invention further relates to methods, compounds, and compositions for the treatment of a variety of neurological disorders.

Abstract: Methods for selecting chemotherapeutic agents for treating a cancer are provided that include the steps of providing a cancer cell sample having a population of bulk cancer cells and a population of cancer stem-like cells, culturing a first portion of the cancer cell sample in a hydrodynamic focusing bioreactor under microgravity conditions and for a period of time to selectively enhance the population of cancer stem-like cells and selectively kill the population of bulk cancer cells, contacting the cancer stem-like cells with one or more chemotherapeutic agents, and then selecting the one or more chemotherapeutic agents for treating the cancer if there is an increase in an amount of cytotoxicity. Methods for treating a cancer are also provided in which the identified chemotherapeutic agents are administered to a subject. Further provided are methods for identifying a test compound useful for treating a cancer.

Abstract: Various 14-nitro, 14-amino, and 14-substituted amino camptothecin derivatives are useful in the treatment of cancer and other hyperproliferative diseases. 14-Nitro camptothecin derivatives are conveniently prepared by reacting a camptothecin derivative with fuming nitric acid, optionally employing acetic anhydride as a solvent.

Abstract: The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.

Abstract: The disclosure includes hydroxamic compounds of Formula I: (Formula I) wherein Z, L, R1, R2, and R3 are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.

Abstract: Self-assembled gel compositions including a gelator, e.g., an enzyme-cleavable gelator, e.g., having a molecular weight of 2500 or less, are described. The self-assembled gel compositions can encapsulate one or more agents. Methods of making the self-assembled gel compositions, and methods of drug delivery using the self-assembled gel compositions are also described.

Abstract: The present invention provides methods for the prevention, treatment and/or amelioration of fibrosis or fibrotic conditions. The present invention further provides small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling to prevent, treat and/or ameliorate fibrosis or fibrotic conditions. Kits comprising small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling and methods of identifying small molecule inhibitors of Wnt- and TGF-p-mediated ?-catenin signaling are also provided.

Abstract: Provided herein are methods, compositions and kits for the treatment of locally advanced or metastatic breast cancer or breast cancer brain metastases. The method comprises administration of 4-iodo-3-nitrobenzamide, a metabolite or salt thereof in combination with irinotecan. The method of treating locally advanced or metastatic breast cancer comprises at least one 21 day treatment cycle.

Abstract: A thermosensitive hydrogel for coating radioisotopes and chemotherapeutic agents to treat cancer and a method for preparing the same are revealed. The anticancer drugs such as radiopharmaceuticals or chemotherapeutic agents are coated with the hydrogel formed by PCL-PEG-PCL. By the feature of the hydrogel body that changes from liquid phase at low storage temperature to gel form at body temperature, not only the anticancer drugs can be injected into the human body and reaching the treatment site smoothly but the treatment time of brachytherapy is also extended. Thus the side effects of cancer therapy are significantly reduced.

Abstract: The invention provides a combination therapy wherein one or more other therapeutic agents are administered with an organic arsenical, preferably SGLU-I or a pharmaceutically acceptable salt thereof. The invention also relates to methods for the treatment of cancer, comprising administering SGLU-I in combination with another therapeutic agent. Another aspect of the invention relates to a kit comprising SGLU-I and another therapeutic agent.

Abstract: The subject invention concerns materials and methods for treating or preventing a neurodegenerative condition or disease associated with ?-amyloid peptide deposition in neural tissue in a person or animal by administering a therapeutically effective amount of a polyphenol, or an analog, isomer, metabolite, or prodrug thereof, that increases expression or activity of a protein that exhibits ?-secretase activity. The subject invention also provides methods to increase ?-secretase expression and/or activity in cells by administering polyphenol flavonoids like (?)-epigallocatechin-3-gallate (EGCG) and epicatechin (EC), two polyphenols derived from green tea and other plants and that can be produced synthetically. Furthermore, there are provided methods to decrease or inhibit the production of A?1-40 or A?1-42 by administering the EGCG and EC compounds, their analogs, metabolites, and prodrugs.

Abstract: The present invention relates to conjugate comprising a carrier substituted with one or more occurrences of a moiety having the structure: wherein each occurrence of M is independently a modifier having a molecular weight ?10 kDa; denotes direct of indirect attachment of M to linker LM; and each occurrence of LM is independently an optionally substituted succinamide-containing linker, whereby the modifier M is directly or indirectly attached to the succinamide linker through an amide bond, and the carrier is linked directly or indirectly to each occurrence of the succinamide linker through an ester bond. In another aspect, the invention provides compositions comprising the conjugates, methods for their preparation, and methods of use thereof in the treatment of various disorder, including, but not limited to cancer.

Abstract: Compounds of Formula I are useful for inhibition of CHK1 and/or CHK2. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract: Provided herein are compounds, compositions, including pharmaceutical compositions, having anti-cancer activity. Also provided are methods for diagnosing, detecting, and treating cancer in a subject, as well as a method for evaluating cancer stage in a subject, wherein the methods include determining the amount of a Ca2+/calmodulin dependent kinase kinase (CaMKK) in a sample. Further provided are methods of screening and identifying a compound that inhibits CaMKK.

Abstract: The present invention relates to a pharmaceutical composition comprising a pharmaceutical agent and a pharmaceutically acceptable carrier, which carrier comprises a protein, for example, human serum albumin and/or deferoxamine. He human serum albumin is present in an amount effective to reduce one or more side effects associated with administration of the pharmaceutical composition. The inventor also provides methods for reducing on or more side effects of administration of the pharmaceutical composition, and methods for enhancing transport and binding of a pharmaceutical agent to a cell.

Abstract: The present disclosure generally relates to nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol. Other aspects of the invention include methods of making such nanoparticles.

Abstract: Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused, five-membered ring. Methods for making the polycyclic alkaloids are disclosed, as well as methods for their use as prophylactics or treatments for certain diseases. Also disclosed are pharmaceutical compositions comprising the polycyclic alkaloids and their use.

Abstract: Novel compounds and pharmaceutical compositions are provided. In one aspect of the invention the compounds may be utilized in medical practice, for example, in treatment of cancer and immune disorders.

Abstract: Among other aspects, provided herein is a hydrohalide salt of a multi-arm water-soluble polyethylene glycol-drug conjugate, along with related methods of making and using the same. The hydrohalide salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding free base form of the conjugate.

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: Disclosed are new substituted oxazole and thiazole compounds of Formula (I) and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses thereof:

Abstract: This document provides methods and materials involved in assessing responsiveness to PARP inhibitors and platinating agents. For example, methods and materials for using levels of non-homologous end-joining pathway members (e.g., artemis mRNA or polypeptide levels, Ku80 mRNA or polypeptide levels, or DNA-PKcs mRNA or polypeptide levels) to determine if cancer cells that are homologous recombination-deficient are likely to be susceptible or resistant to PARP inhibitors and platinating agents are provided.

Abstract: Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are noscapine analogs. The compounds and compositions can be used to treat and/or prevent a wide variety of cancers, including drug resistant cancers. While the antitussive plant alkaloid, noscapine, binds tubulin, displays anticancer activity, and has a safe pharmacological profile in humans, structure-function analyses pointed to a proton at position 9 of the isoquinoline ring that can be modified without compromising tubulin binding activity. Noscapine analogs with various functional moieties at position 9 on the isoquinoline ring kill human cancer cells resistant to other anti-microtubule agents, such as vincas and taxanes.

Abstract: New substituted benzazole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.

Abstract: The present disclosure relates in part to pharmaceutical compositions comprising polymeric nanoparticles having certain glass transition temperatures. Other aspects of the invention include methods of making such nanoparticles.

Abstract: In the present invention there is provided a pharmaceutical composition for oral administration which comprises bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient and which shows a dissolution of the bendamustine of at least 60% in 20 minutes, 70% in 40 minutes and 80% in 60 minutes, as measured with a paddle apparatus at 50 rpm according to the European Pharmacopoeia in 500 ml of a dissolution medium at a pH of 1.

Abstract: In the present invention there is provided an oral pharmaceutical composition, comprising bendamustine or a pharmaceutically acceptable, ester, salt or solvate thereof as an active ingredient, and a pharmaceutically acceptable excipient, which is a pharmaceutically acceptable non-ionic hydrophilic surfactant.

Abstract: The present disclosure generally relates to therapeutic nanoparticles. Exemplary nanoparticles disclosed herein may include about 1 to about 20 weight percent of a vinca alkaloid; and about 50 to about 99 weight percent biocompatible polymer.

Abstract: Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.

Abstract: Methods of treating, preventing and/or managing cancer as well as and diseases and disorders associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

Abstract: A method of treating cancer in a subject in need thereof comprises administering said subject reserpine, yohimbine, an analog thereof, or a pharmaceutically acceptable salt or prodrug thereof, in an amount effective to treat the cancer. Compounds and compositions useful for carrying out the method are also described.

Abstract: The invention relates to a novel therapeutic use of 14,15-dihydro-20,21-dinoreburnamenin-14-ol for the treatment of serious depression in humans, particularly for the treatment of a patients resistant to conventional anti-depressant treatments and for treatment of sleep/waking cycle disorders.

Abstract: Novel Uses of an aromatic ester isolated from Armillaria mellea, particularly, armillaridin, are disclosed herein. The armillaridin is useful for manufacturing a medicament or a pharmaceutical composition for suppressing the growth of cancerous cells or for enhancing susceptibility of esophageal cancerous cells to a radiation treatment, in a subject.

Abstract: This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

Abstract: A liquid composition of an insoluble medicament and a preparation method thereof are disclosed. The composition includes insoluble medicament, oil for injection, phospholipid, and solvent; the percentage by weight of each component is as follows: insoluble medicament 0.01-10%, oil for injection 0%-20%, phospholipid 10-80%, solvent 20-89%. The preparation method for the composition includes the following steps: dissolving an insoluble medicament into solvent or oil for injection or a mixture thereof firstly, and then adding other components, and mixing uniformly; or dissolving an insoluble medicament into a mixture of other components, and mixing uniformly; or dissolving an insoluble medicament into part of solvent firstly, and then adding into a mixed solvent of other components and the remaining solvent, and mixing uniformly.

Abstract: Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.