Abstract: Concentrated liquid pharmaceutical compositions comprising a) a pharmaceutically effective amount of bendamustine or a pharmaceutically acceptable salt thereof, b) a non-aqueous solvent, and c) at least about 2% water, suitable, after dilution, for administration to a mammal by injection are provided. The concentrated liquid pharmaceutical compositions can comprise a non-aqueous solvent comprising at least one organic polymeric compound solvent and at least one organic small molecule solvent. Methods of treating a cancer in a mammal in need of such treatment comprising administering to the mammal an effective amount of a concentrated liquid bendamustine pharmaceutical composition of the invention are also provided.

Abstract: The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of HPK1, and the treatment of HPK1-mediated disorders.

Abstract: Stable, injectable pharmaceutical compositions are provided, which are useful as ready-to-dilute (RTD) or ready-to-use (RTU) liquid injectable compositions comprising bendamustine or a pharmaceutically acceptable salt thereof, and which are suitable for intravenous administration. Preferably, solution formulations comprise (a) bendamustine, or pharmaceutically acceptable salts, solvates, or hydrates thereof, (b) at least one pharmaceutically acceptable non-aqueous solvent; (c) optionally, at least one pharmaceutically acceptable excipient, and (d) optionally, a pH adjuster, where the pharmaceutical composition is antioxidant-free, and formulated as a ready-to-dilute or ready-to-use liquid composition suitable for parenteral administration. The invention further relates to methods for manufacturing stable, antioxidant-free injectable solutions of bendamustine.

Abstract: The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (ROR?) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of ROR?-mediated diseases or disorders.

Abstract: The present invention relates to a liquid pharmaceutical formulation, which is stable at room temperature, being essentially free of water, comprising a) at least one easily degradable active pharmaceutical ingredient, b) at least one pharmaceutically acceptable organic solvent and c) at least one pharmaceutically acceptable alkaline earth metal salt and its use in medicine.

Abstract: The present invention provides a pharmaceutical composition comprising clopidogrel or pharmaceutically acceptable salts thereof; and tegoprazan or pharmaceutically acceptable salts thereof as an active ingredient. The pharmaceutical composition of the present invention has an advantage of maintaining a medicinal effect of clopidogrel while preventing or treating a side effect of clopidogrel, i.e., gastrointestinal disorders.

Abstract: Provided herein are pharmaceutical compositions that are useful for the treatment of hypertension comprising an angiotensin II receptor blocker, a diuretic, and a calcium channel blocker.

Abstract: Stable, injectable pharmaceutical compositions are provided, which are useful as ready-to-dilute (RTD) or ready-to-use (RTU) liquid injectable compositions comprising bendamustine or a pharmaceutically acceptable salt thereof, and which are suitable for intravenous administration. Preferably, solution formulations comprise (a) bendamustine, or pharmaceutically acceptable salts, solvates, or hydrates thereof, (b) at least one pharmaceutically acceptable non-aqueous solvent; (c) optionally, at least one pharmaceutically acceptable excipient, and (d) optionally, a pH adjuster, where the pharmaceutical composition is antioxidant-free, and formulated as a ready-to-dilute or ready-to-use liquid composition suitable for parenteral administration. The invention further relates to methods for manufacturing stable, antioxidant-free injectable solutions of bendamustine.

Abstract: This application relates to substituted benzimidazoles, compositions comprising them and their uses in the treatment of diseases and conditions in which inhibition of a bromodomain is indicated. For example, the application relates to substituted benzimidazoles and to their use as bromodomain inhibitors. The present application is also related to the treatment or prevention of proliferative disorders, auto-immune disorders, inflammatory disorders, dermal disorders, and neoplasms, including tumors and/or cancers.

Abstract: Personalized medicine involves the use of a patient's molecular markers to guide treatment regimens for the patient. The scientific literature provides multiple examples of correlations between drug treatment efficacy and the presence or absence of molecular markers in a patient sample. Methods are provided herein that permit efficient dissemination of scientific findings regarding treatment efficacy and molecular markers found in patient tumors to health care providers.

Abstract: This invention relates to methods and compositions for treatment of inv (16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv (16) leukemia comprising the step of administering to a subject in in need thereof a therapeutically effective combination of a) a compound of the formula (1) (1) and b) a BRD4 inhibitor selected from the group consisting of JQ1, CeMMECZ, 1-BET 151 (or GSK1210151A), 1-BET 762 (or GSK525762), PFI-1, bromosporine, OTX-015 (or MK-8628), TEN-010, CPI-203, CPI-0610, RVX-208, BI2536, TG101348, LY294002, ABBV-075 (or mivebresib), FT-1101, ZEN003694, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv (16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the BRD4 inhibitor and a pharmaceutically acceptable excipient.

Abstract: Long term storage stable bendamustine-containing compositions are disclosed. The compositions can include bendamustine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable fluid which can include in some embodiments PEG, PG or mixtures thereof and an antioxidant or chloride ion source. The bendamustine-containing compositions have less than about 5% total impurities, on a normalized peak area response (“PAR”) basis as determined by high performance liquid chromatography (“HPLC”) at a wavelength of 223 nm, after at least about 15 months of storage at a temperature of from about 5° C. to about 25° C.

Abstract: Stable, injectable pharmaceutical compositions are provided, which are useful as ready-to-dilute (RTD) or ready-to-use (RTU) liquid injectable compositions comprising bendamustine or a pharmaceutically acceptable salt thereof, and which are suitable for intravenous administration. Preferably, solution formulations comprise (a) bendamustine, or pharmaceutically acceptable salts, solvates, or hydrates thereof, (b) at least one pharmaceutically acceptable non-aqueous solvent; (c) optionally, at least one pharmaceutically acceptable excipient, and (d) optionally, a pH adjuster, where the pharmaceutical composition is antioxidant-free, and formulated as a ready-to-dilute or ready-to-use liquid composition suitable for parenteral administration. The invention further relates to methods for manufacturing stable, antioxidant-free injectable solutions of bendamustine.

Abstract: There is provided tinostamustine or a pharmaceutically acceptable salt thereof for use in the treatment of triple negative breast cancer (TNBC) to a patient in need thereof.

Abstract: The present invention includes a method of inhibiting or reducing deregulated FLT3 tyrosine kinase activity or FLT3 tyrosine kinase expression in a subject with a proliferative disease by administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I: or pharmaceutically acceptable salt thereof.

Abstract: Stable, injectable pharmaceutical compositions are provided, which are useful as ready-to-dilute (RTD) or ready-to-use (RTU) liquid injectable compositions comprising bendamustine or a pharmaceutically acceptable salt thereof, which are suitable for intravenous administration. Preferably, solution formulations comprise (a) bendamustine or its pharmaceutically acceptable salts, solvates, or hydrates thereof, (b) at least one pharmaceutically acceptable non-aqueous solvent; (c) optionally, at least one pharmaceutically acceptable excipient, and (d) optionally, a pH adjuster, where the pharmaceutical composition is antioxidant-free, and formulated as a ready-to-dilute or ready-to-use liquid composition suitable for parenteral administration. The invention further relates to methods for manufacturing stable, antioxidant-free injectable solutions of bendamustine.

Abstract: The present invention includes methods for treating TRKA, TRKB, and/or TRKC driven proliferative disorder in a subject comprising administering to the subject a therapeutically effective amount of crenolanib, wherein the subject has a proliferative disorder with overexpression, activation, amplification, or mutation of TRKA, TRKB, and/or TRKC kinase.

Abstract: Solutions comprising a glycopeptide antibiotic, for example Vancomycin, and an amino acid or amino acid derivative such as N-acetyl-Glycine or N-acetyl-D-Alanine are provided. These solutions are stable or stabilized for long-term periods at conditions of normal use and storage, and can be formulated as pharmaceutical solutions for use in subjects. Methods of manufacturing and using these solutions are also provided, as are methods of stabilizing a glycopeptide antibiotic, for example Vancomycin, using amino acids or amino acid derivatives such as N-acetyl-Glycine or N-acetyl-D-Alanine.

Abstract: The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (ROR?) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of ROR?-mediated diseases or disorders.

Abstract: There is provided tinostamustine or a pharmaceutically acceptable salt thereof for use in the treatment of triple negative breast cancer (TNBC) to a patient in need thereof.

Abstract: The present invention relates to benzimidazole compounds and an application thereof as IDH1 mutant inhibitors, in particular, to a compound as represented by formula (I), tautomers thereof, or pharmaceutically acceptable salts thereof.

Abstract: The instant disclosure provides methods and compositions related to discovery that topical administration of MEK inhibitors for the treatment of skin disorders (e.g., skin cancer, inflammatory skin disorders) is accomplished with markedly reduced dosage levels in comparison with oral administration dosage levels. Therapeutic and/or prophylactic uses and compositions of known MEK inhibitors are described.

Abstract: According to various embodiments of this disclosure, pharmaceutical compositions comprising solubilized estradiol are provided. In various embodiments, such compositions are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy.

Abstract: The invention provides compounds of formula (I): and salts thereof wherein R1-R5 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).

Abstract: The invention relates to c-Kit inhibitors useful in the treatment of cancers, and other serine-threonine kinase mediated diseases, having the Formula: (I) where A, L, R1, R2, R3, and n are described herein.

Abstract: The invention discloses compositions, methods and kits for use in treatment of diseases associated with CNS inflammation such as multiple sclerosis. The composition includes therapeutically effective amount of (1-H indazole-4yl-)methanol. Further, a method of inhibiting glial maturation factor beta (GMF-?) phosphorylation activity in cells is disclosed. The method of treating subjects includes administering a therapeutic effective amount of the composition. The administered composition suppresses the activity of the overexpressed GMF-? either by binding or blocking its phosphorylating sites and ameliorating the inflammatory condition. The disclosed compositions, methods and kits may be used in the treatment of diseases like multiple sclerosis, Alzheimer's disease, Parkinson's disease or cancer.

Abstract: Methods of using the alpha-2-adrenergic receptor agonist of Formula I: for improving vision such as in the treatment of ocular conditions such as presbyopia, poor night vision, visual glare, visual starbursts, visual halos, and some forms of myopia (e.g. night myopia) are described.

Abstract: The disclosure provides compounds of Formula (I), wherein X, Y, and Z are defined herein. The disclosure also provides particles comprising one or more compounds described herein, compositions comprising one or more compounds or particles described herein and a pharmaceutically acceptable carrier, and methods of treating a subject in need thereof comprising administering one or more compounds, particles, or compositions described herein to the subject. X—Y—Z??(I).

Abstract: The present invention relates to imidazoyl urea polymers and their use in aqueous acidic plating baths for metal or metal alloy deposition such as electrolytic deposition of copper or alloys thereof in the manufacture of printed circuit boards, IC substrates, semiconducting and glass devices for electronic applications. The plating bath according to the present invention comprises at least one source of metal ions and an imidazoyl urea polymer. The plating bath is particularly useful for filling recessed structures and build-up of pillar bump structures.

Abstract: Systems and methods for rapid gene set enrichment analysis and applications thereof are described. In certain embodiments, the systems and methods described herein may be used to identify one or more candidate therapies for treatment of a disease (e.g., cancer). These systems and methods enable improved prioritization of relevant gene sets while maintaining a relatively lower false positive rate. Additionally, the ability to accelerate enrichment analysis and analyze hundreds of thousands of gene sets is described.

Abstract: Provided are methods for treating cancer in a patient by administering at least one antibiotic selected from the group consisting of clofazimine, rifabutin and clarithromycin, in combination with an aryladamantane compound. In an embodiment, the aryladamantane compound is [3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide], or a pharmaceutically acceptable salt thereof.

Abstract: Provided are indole, benzoimidazole, pyrrolopyridine, and imidazopyridine derivatives and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by ROR?. Such derivatives include e.g., those having the Formula II: as well as pharmaceutically acceptable salts thereof. The disclosed derivatives may be used for treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

Abstract: Novel rexinoid compounds are provided herein. Also provided herein are methods of using the compounds to treat disorders, such as metabolic disorders, diabetes, insulin resistance, glucose intolerance, obesity, steatosis, inflammation, and/or cancer.

Abstract: The present invention includes a method of inhibiting or reducing deregulated FLT3 tyrosine kinase activity or FLT3 tyrosine kinase expression in a subject with a proliferative disease by administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I: or pharmaceutically acceptable salt thereof.

Abstract: 2-(5-{1-[2-(Difluoromethoxy)-6-fluorobenzyl]-2-methyl-1H-benzimidazol-6-yl}pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof, being potent modulators of human TNF? activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Abstract: In one aspect, methods of treating non-alcoholic steatohepatitis (NASH) or preventing or delaying the progression of non-alcoholic fatty liver disease (NAFLD) to NASH are provided. In some embodiments, the method comprises administering a therapeutically effective amount of ubenimex.

Abstract: Amine substituted pyridine and pyrazine compounds and forms thereof that inhibit the function and reduce the level of B-cell specific Moloney murine leukemia virus integration site 1 (Bmi-1) protein and methods for their use to inhibit Bmi-1 function and reduce the level of Bmi-1 to treat a cancer mediated by Bmi-1 are described herein.

Abstract: The present disclosure provides an edible gelatin base film and preparation method thereof, relating to material fields. The preparation method can improve the mechanical property of the film. The films prepared by the method have antibacterial properties, low-temperature stability and high-temperature dissolution, environmental-friendly components. The method includes the following steps: a) preparing gel nanoparticles; b) preparing bacterial cellulose nanoparticles; c) preparing the gelatin base film: mixing pullulan, glycerin, nisin, antibacterial peptide, the gel nanoparticles obtained from step a) and the bacterial cellulose nanoparticles obtained from step b), ultrasonically degassing, then being subjected to coating and drying to obtain the gelatin base film. The preparation method is used to prepare an edible gelatin base film.

Abstract: Disclosed herein is, among other things, a soft gel vaginal pharmaceutical composition and dosage form containing solubilized estradiol for the treatment of vulvovaginal atrophy (VVA) and female sexual dysfunction (FSD).

Abstract: Topical composition for the treatment of mucosal lesions It relates to a topical composition comprising specific amounts of: a) a hyaluronic acid or a pharmaceutically or veterinary acceptable salt thereof, b) one or more adhesive agents, and c) a non-absorbable antibiotic; to delivery devices comprising it; and to its uses in medicine, in particular, in the treatment and/or prevention of mucosal lesions; in the prevention of postpolypectomy syndrome; as adjuvant therapy to mechanical treatments in gastrointestinal perforations, and as sealant treatment in surgical anastomoses and leaks or fistulas in gastrointestinal tract.

Abstract: According to various embodiments of this disclosure, pharmaceutical compositions comprising solubilized estradiol are provided. In various embodiments, such compositions are encapsulated in soft capsules which may be vaginally inserted for the treatment of vulvovaginal atrophy.

Abstract: Provided are a phosphodiesterase-4 (PDE4) inhibitor and application thereof in preparation of a medication for treating a disease related to PDE4. Specifically disclosed is a compound as shown in formula (I) and a pharmaceutically acceptable salt thereof.

Abstract: A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I: comprising a copper-catalyzed, carbon-nitrogen cross-coupling step. The process described as part of the present invention can be used to manufacture poly (ADP-ribose) polymerase (PARP) inhibitors, which may be useful for the treatment of cancer. In particular, the present invention describes a process for the manufacture of the PARP inhibitor, 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide.

Abstract: The present invention is directed to a combination comprising a proteasome inhibitor and a compound of formula I or a pharmaceutically acceptable salt thereof: to a pharmaceutical composition and to a kit both comprising said combination, to the combination, composition or kit for use in the treatment of cancer, and to a method of treatment of cancer in a patient in need thereof comprising administering to said patient an effective amount of said combination, composition or kit.

Abstract: The present invention relates to the technical field of medicinal chemistry, and in particular discloses a 2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof. The compound and pharmaceutically acceptable salt, isomer, racemate, prodrug, co-crystallized complex, hydrate, and solvate thereof can effectively inhibit the BET bromodomain receptor, and can be used for preparing a medicine for treating cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections.

Abstract: The present invention relates to 2-Aryl- and 2-Arylalkyl-benzimidazoles of general formula (I): in which A, R1, R4, R5, R6, R7, R8, R9, R10 and R11 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

Abstract: Use of acetylated tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazoles compound of general formula (I).

Abstract: The present invention relates to compounds of the formula (I) wherein Ar1 and Ar2 are as described in the description and to their use as pharmaceuticals for the treatment of sundown syndrome. The invention also relates to the preparation of such compounds and of pharmaceutically acceptable salts thereof.

Abstract: Antimicrobial inks, sealants, coatings or varnishes that are manufactured in three distinct phases: Phase 1, which is an oil phase comprising Ethoxylate Alcohol Laureth 7, Didecyldimethylammonium chloride, Glutaric acid dialdehyde, Pinus sylvestris, Alkyldimemylberizylammonium chloride, Parachlorometaxylenol, Ethylenediaminetetraacetic acid, 2-Hydroxypropanoic acid, Hydroxy-9-cis-octadecenoic acid, Cetyl alcohol wax, Octadecenoic acid, Palmityl alcohol, and Epoxy-cis-9-octadecenoic acid; Phase 2, which is a micro-emulsion phase comprising Ethoxylate Alcohol Laureth-7, Cetyl alcohol wax, Pinus sylvestris, and Propan-2-ol and Phase 3, which combines the products of Phases 1 and 2 with a base to produce the ink, sealant, coating or varnish.

Abstract: The present invention relates to novel 2,5,6-benzimidazole derivatives and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to methods of treating a patient infected by Mycobacterium tuberculosis by administering to the patient a 2,5,6-benzimidazole derivative or a pharmaceutically acceptable salt thereof.