Abstract: The present invention relates to a therapeutic agent for gait disturbance in a patient with ischemic disease, containing, as an active ingredient, a heterocyclic derivative represented by formula (1) or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are the same or different and each represents optionally substituted aryl; R3 and R4 are the same or different and each represents a hydrogen atom or alkyl; R5 represents a hydrogen atom, alkyl, or a halogen atom; Y represents N or N->0; A represents NR6 and R6 represents a hydrogen atom, alkyl, or the like; D represents alkylene or alkenylene optionally substituted with hydroxy; E represents phenylene or a single bond; G represents O, S, or the like; and Q represents carboxy, alkoxycarbonyl, or the like.

Abstract: Described herein are compositions and methods for the prevention or treatment of osteoarthritis by administrating a therapeutically effective amount of at least one SHP2 antagonistic agent to the subject. The SHP2 antagonistic agent can be a SHP2 inhibitor, a PROTAC degrader of SHP2 proteins, and/or a SHP2 RNA interference or a small interfering RNA, or a combination thereof.

Abstract: [Problem] To provide: a novel tetrahydroisoquinoline (THIQ) alkaloid compound having a macrocyclic structure; an intermediate of the compound; and a method for producing the compound. [Solution] Provided is a compound represented by formula (I), or a pharmaceutically acceptable salt thereof. The present invention also provides: a method for synthesizing this compound; and an intermediate compound useful in this synthesis.

Abstract: The invention relates to novel solid dispersions comprising amorphous pimobendan and one or more stabilizing polymers as well as processes of manufacturing thereof and corresponding pharmaceutical compositions.

Abstract: Cation chloride cotransporters (CCC) play a critical role in neuronal chloride homeostasis. Altered CCC expression and function has emerged as a hallmark of wide range of psychiatric and neurological conditions, including various forms of epilepsy. Elevated intraneuronal chloride concentration is thought to result in depolarizing GABA signaling that may contribute to pathological activities and seizures. Compensating for the dysregulation of CCC function in the pathology therefore appears as a promising therapeutic strategy. Bumetanide, an antagonist of the Na/K/Cl co-transporter NKCC1 failed to prevent acute neonatal seizures in the NEMO trial. Here, instead, the inventors tested the effects of novel candidate KCC2 enhancers on epileptiform activity in vitro and in vivo. The inventors show that FDA-approved prochlorperazine (PCPZ) as well as CLP257 potentiate KCC2 function by promoting its membrane clustering, through a mechanism/pathway that does not involve phosphorylation of canonical residues.

Abstract: Provided herein are compounds (e.g., compounds of Formulae (I), (II), (III) and (IV), compounds listed in Table 1) and pharmaceutically acceptable salts thereof, pharmaceutical compositions of either of the foregoing, and kits comprising the same. The compounds provided herein are activin receptor-like kinase (e.g., ALK-5) inhibitors and are useful for treating and/or preventing diseases (e.g., proliferative diseases, e.g., cancer) in a subject, for inhibiting tumor growth in a subject, and/or for inhibiting the activity of an activin receptor-like kinase (e.g., ALK-5) in vitro or in vivo.

Abstract: Provided include methods, compositions and kits for treating cancer in a subject. The method can comprise administrating a PARP inhibitor (for example, olaparib) and a PLK1 inhibitor (for example, onvansertib) to the subject in a manner sufficient to inhibit progression of the cancer.

Abstract: This invention relates to methods comprising administering a FAK inhibitor (e.g., VS-6063) in combination with a dual RAF/MEK inhibitor (e.g., CHS 126766) that are useful in the treatment of abnormal cell growth, such as cancer, in a subject such as humans.

Abstract: The present disclosure relates to oral compositions of Compound I or a derivative thereof. Methods of use for treating an inflammatory condition are also disclosed.

Abstract: The present invention relates to the use of 2-(3-(3-(2,4-dimethoxypyrimidin-5-yl)phenyl)-3H-imidazo[4,5-b]pyridin-6-yl)propan-2-ol or a pharmaceutically acceptable salt thereof, which is a known GABA receptor modulator, for the treatment of disorders characterized by severe pain, such as trigeminal neuralgia and postoperative pain.

Abstract: Compositions and methods for the treatment of hair growth and the prevention of hair loss.

Abstract: The present invention is directed to the combination therapy of cancer with a BRAF inhibitor and a PD-1 axis binding anatgonist.

Abstract: Various methods and compositions for treating single ventricle heart disease (SVHD) patients, including patients who have undergone Fontan surgery and who have Fontan circulation (Fontan patient), to improve exercise performance, single ventricular performance, cardiac output and myocardial performance index (MPI) in the SVHD patients, including the Fontan patients, using udenafil compositions. In one exemplary embodiment, the methods of the present invention include administering an effective amount of udenafil or a pharmaceutically acceptable salt thereof to a SVHD patient, including a Fontan, to improve the ventricular performance of the SVHD patient's, including the Fontan patient's, single functioning ventricle. In another exemplary embodiment, the methods of the present invention include administering an effective amount of udenafil or a pharmaceutically acceptable salt thereof to a SVHD patient, including a Fontan patient, to improve the SVHD patient's, including the Fontan patient's, MPI.

Abstract: An application of a compound having a structure represented by chemical formula 1, a pharmaceutically acceptable salt thereof, a solvate thereof, a solvate of the pharmaceutically acceptable salt thereof, or a crystal form thereof, in particular an application thereof in the preparation of an inhibitory drug targeting an ErbB2 mutant. The provided compound has inhibitory activity against the ErbB2 mutant, and can effectively inhibit proliferation of ErbB2 mutation tumor cells.

Abstract: Disclosed are compositions for targeting 0TUD7A, the compositions having a component sufficient to block and/or reduce OTUD7A-mediated deubiquitination of EWS-FLI1 in a cell. The component can be 7Ai and variants thereof. The compositions can be used to treat Ewing sarcoma (EWS). Methods of using the disclosed compositions are also disclosed, including methods of treating EWS in a subject.

Abstract: Herein are provided a combination of ribociclib, or a pharmaceutically acceptable salt thereof, such as ribociclib succinate, and amcenestrant, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing such a combination, and the therapeutic uses thereof, in particular for the treatment of cancer, including breast cancer.

Abstract: The present disclosure provides compositions of methotrexate for ocular administration, including intravitreal administration, and use of the formulations for treating proliferative vitreoretinopathy (PVR), uveitis, macular edema, and uveitic macular edema.

Abstract: An external anti-inflammatory drug compound, and a preparation method therefor and the use thereof. The structural formula of the compound is A-Y—B, wherein A is a group after dehydrogenation of an amine compound having JAK inhibitory activity, Y is a direct connection or —(CH2)—O— or, and B is a group formed by means of dehydroxylation of a carboxy-containing carboxylic acid compound B1, or a group formed by means of dehydrogenation of a hydroxy-containing compound B2. The compound has the special effects of having a strong transdermal property, controlled drug release, high efficacy, etc.

Abstract: Therapeutic combinations of a CD 19 inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a CD 19 inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer, such as a hematological malignancy. A combination of a BTK inhibitor and a CD 19 inhibitor, such as a CD19-targeted antibody or a CD19-targeted chimeric antigen receptor expressing T cell or NK cell, and compositions and uses thereof are disclosed. Combinations of a BTK inhibitor and a CD 19 inhibitor with a programmed death-1 (PD-1) or PD-1 ligand (PD-L1) inhibitor and compositions and uses thereof are also disclosed.

Abstract: Disclosed herein is a method for treating a subject having uterine serous carcinoma with a WEE1 inhibitor, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides methods, kits, and compositions for treating sex steroid dependent cancer using BMX inhibitors. In certain embodiments, a sample from a subject having, or suspected of having, a sex steroid dependent disease cancer, is further assayed to determine: i) if the subject is heterozygous or homozygous for the HSD3B1(1245C) allele that encodes for the 3?SD1(367T) protein. In some embodiments, the BMX inhibitor comprises a monoclonal antibody or BMX binding portion thereof (e.g., zanubrutinib, acalabrutinib, abivertinib or ibrutinib).

Abstract: Disclosed is a method for preventing, delaying or reversing age-associated inflammation, by administering to a patient in need thereof a therapeutically effective amount of at least one reverse transcriptase inhibitor (RTI).

Abstract: A method of treating colorectal cancer (CRC) is provided. The method comprises administering to a subject in need thereof a therapeutically effective amount of a Mitogen/extracellular signal-regulated kinase (MEK) inhibitor and a SRC Proto-Oncogene, Non-Receptor Tyrosine Kinase (SRC) inhibitor, wherein cancer cells of the subject express an amount of SRC p419 above a predetermined level and do not express a KRAS G12 mutation, thereby treating the CRC.

Abstract: The present invention relates to methods of treating viral infections including COVID-19 and compositions with a combination of (i) an inhibitor of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and (ii) an inhibitor of transmembrane serine proteinase 2 (TMPRSS-2).

Abstract: Combination Treatments for Melanoma This specification discloses the use of an ATR inhibitor in combination with an immune checkpoint inhibitor for the treatment of melanoma in a patient who has previously received immunotherapy.

Abstract: The present invention relates to a method of inhibiting lipogenesis with a ubiquitin-specific peptidase 24 (USP24) inhibitor composition. The USP24 inhibitor composition, which includes a carbonyl substituted phenyl compound, can specifically inhibit lipogenesis and hepatic lipid accumulation in a high-fat individual, thereby being applied to a method of inhibiting lipogenesis and hepatic lipid accumulation in a high-fat subject.

Abstract: Disclosed herein are dosing regimens of ceftibuten in combination with a ?-lactamase inhibitor. The dosing regimens include ceftibuten at a dose higher than 400 mg per day (for example, 400 mg BID, 600 mg QD or BID, or 800 mg QD or BID).

Abstract: The present invention discloses a pharmaceutical composition, wherein the pharmaceutical composition is an injectable or infusable pharmaceutical composition, the pharmaceutical composition comprising: a) a pharmaceutically acceptable solvent, b) a first compound comprising diclofenac or a pharmaceutically acceptable salt or solvate thereof, c) a second compound comprising metamizole or tramadol or a pharmaceutically acceptable salt or solvate thereof, and d) a third compound selected as at least one benzodiazepine or a pharmaceutically acceptable salt or solvate thereof, the pharmaceutical composition further comprising a cortisone derivative or a pharmaceutically acceptable salt or solvate thereof.

Abstract: Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.

Abstract: An object is to provide a pharmaceutical composition that improves cardiac function when administered during coronary artery bypass surgery for ischemic cardiomyopathy. A pharmaceutical composition for improving cardiac function comprising: (A) a release formulation comprising at least poly(lactic-co-glycolic acid) (PLGA) and a prostaglandin 12 receptor agonist, the PLGA having an average molecular weight of 10000 to 30000; and (B) a release formulation comprising at least poly(lactic-co-glycolic acid) (PLGA) and a prostaglandin 12 receptor agonist, the PLGA having an average molecular weight of 40000 to 60000.

Abstract: The present invention relates to methods of preventing, inhibiting, delaying. and/or mitigating seizures by administration of a steroid, e.g., a neurosteroid, e.g., allopregnanolone.

Abstract: The invention relates to a pharmaceutical composition, characterised in that it comprises, as an active substance, a combination of beta-elemene, lupeol and a pharmaceutically active agent selected from cinnamaldehyde, 2-hydroxycinnamaldehyde, 2?- benzoyloxycinnamaldehyde, beta-sitosterol, curcumin and the mixtures thereof.

Abstract: The disclosure relates to methods of treating depression, pain, a musculoskeletal disorder or a motor disorder such as essential tremor with Compound 1 or pharmaceutically acceptable salts thereof.

Abstract: The invention relates to a pharmaceutical dosage form which comprises a solid dispersion product comprising N—(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl) propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide or a salt, hydrate or solvate thereof, at least one pharmaceutically acceptable polymer, and at least one pharmaceutically acceptable solubilizer. The invention is further directed to processes for preparing the pharmaceutical dosage form and to use of the dosage form for treating proliferative disorders.

Abstract: The present disclosure provides pharmaceutical compositions comprising a therapeutically effective amount of psilocybin and one or more pharmaceutically acceptable excipients. Methods of making such compositions and use thereof in treating depressive disorders are also disclosed.

Abstract: The present invention relates to immune stimulating nanoparticle compositions, and their use in treatment of diseases and disorders, such as cancer. In particular, the present invention relates to nanoparticle compositions comprising a TLR7 agonist, such as 1V270.

Abstract: Methods, agents, and pharmaceutical compositions are provided for treating neurodegenerative disease, for enhancing stroke recovery, and or for inhibiting ferroptosis in a subject. These agents, including 2-deoxyglucose, can be used alone or with the right timing in sequential combination with agents that inhibit the integrated stress response. The present invention addresses these needs and provides methods of treating neurodegenerative conditions, including without the need for dietary restrictions which can be challenging in already unwell patients.

Abstract: Disclosed are methods for treating infectious diseases and cancers comprising administering to a subject a L-fucose.

Abstract: Nutritional composition comprising galacto-oligosaccharide (GOS) and 2?-fucosyllactose (2?-FL) in a GOS:2?-FL weight ratio of 1:9-9:1 for use in increasing the relative abundance of bifidobacteria, preferably Bifidobacterium adolescentis and/or Bifidobacterium longum in the gastro-intestinal tract of a non-infant human subject.

Abstract: Disclosed is a composition for promoting hair growth and ameliorating, preventing or treating hair loss containing 2?-fucosyllactose (2?-FL) as an active ingredient, and a method for promoting hair growth or ameliorating, preventing or treating hair loss, the method comprising administering to a subject in need thereof 2?-fucosyllactose. Treatment with a combination of testosterone and 2?-fucosyllactose increases hair gloss, increases hair length, reduces a hair loss area, enhances hair cuticles, increases the number and size of hair follicles, and improves expression of proteins and genes related to hair proliferation and growth, compared to treatment with testosterone alone, thus being applicable as a substance for various food and pharmaceutical compositions based on effects of promoting hair growth, improving hair loss, and ameliorating, preventing or treating hair loss.

Abstract: A method for inhibiting body fat accumulation comprises a process of taking 3.38 mg or more of oenothein B indicated by the following formula (I) as an effective amount per day. G in the formula (I) represents a structure of the following formula (II).

Abstract: Antiviral liposomal compositions comprising ascorbyl 2-glucoside (AA2G) and other active ingredients including propolis extract and other natural plant extracts, use thereof as an effective medicament, prophylactic, or nutritional supplement against viral infections in general and for treating and or preventing coronavirus disease 2019 (COVID-19) in particular, and methods of preparing such antiviral compositions.

Abstract: The present invention provides compositions, systems, kits, and methods for treating a subject with an RNA virus infection (e.g., SARS-COV-2) by administering or providing a composition comprising a cytidine deaminase inhibitor (e.g., tetrahy-drouridine or cedazuridine).

Abstract: The present invention relates to a combination comprising zidovudine or a pharmaceutically acceptable derivative thereof and a tetracycline antibiotic or a pharmaceutically acceptable derivative or prodrug thereof, for use in treating a microbial infection, particularly a bacterial infection such as a urinary tract infection.

Abstract: Described herein are methods of disrupting (e.g., reducing the viscosity of, or dissolving) a preformed biofilm in a subject, the method comprising: administering to the subject an effective amount of a composition comprising a soluble chitosan or derivatized chitosan wherein the soluble chitosan or derivatized chitosan when administered contacts the preformed biofilm, thereby disrupting (e.g., reducing the viscosity of, or dissolving) the preformed biofilm.

Abstract: Described herein are methods of treating wounds, the method comprising administering to a subject an effective amount of a composition comprising a soluble or derivatized chitosan wherein the soluble or derivatized chitosan when administered contacts the wound, thereby treating the wound.

Abstract: The present disclosure relates to pharmaceutical compositions capable of regulating elastic fiber. The disclosure further relates to methods of treating elastic fiber-related disorders, such as COPD, by inhalation of low-molecular weight hyaluronic acid.

Abstract: The present disclosure relates generally to a topical composition comprising a therapeutically effective combination of (i) cromoglycic acid, or a pharmaceutically acceptable salt thereof, and (ii) hyaluronic acid, or a pharmaceutically-acceptable salt thereof (HA), which is suitable for nasal administration for the treatment of inflammation and wounds.

Abstract: A synthetic composition comprising one or more compounds according to formula (1), or a pharmaceutically acceptable salt, solvate or ester thereof, for use in the modulation of one or more of: i. the cholesterol level; ii. lipolysis; iii. glucose uptake; iv. CD36 receptor activity; wherein the compound of Formula 1 is Yn?D-Gal-?1?3-(Ym?)(Xp?)D-GcNAc-?1?3-D-Gal-?1?4-(Xq?)-D-Glc (Formula (1)), wherein X is ?-L-Fucose (?-L-Fuc), Y is N-acetyl-D-neuraminic acid (Neu5Ac-?-2-), n, m, p, q indicate the number of the monosaccharide residues present in the compound of formula (1) and n is 0 or 1; m is 0 or 1; p is 0 or 1; q is 0 or 1; and n+m+p+q?1.

Abstract: Provided herein are formulations and compositions for ocular diseases or disorders such as dry eye disease. Further provided herein are methods for manufacturing ocular formulations and compositions.