Abstract: Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons of therapy failure are lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression. Thus, the investigation of mechanisms regulating RCC progression is fundamental to improve RCC therapy. In order to identify molecular markers and gene processes involved in the steps of RCC progression, the inventors generated several cell lines of higher aggressiveness by serially passaging mouse renal cancer RENCA cells in mice and, concomitantly, performed functional genomics analysis of the cells. Multiple cell lines depicting the major steps of tumor progression (including primary tumor growth, survival in the blood circulation and metastatic spread) were generated and analyzed by large-scale transcriptome, genome and methylome analyses.

Abstract: Method and compositions that comprise an agent that reduces nNOS Open arm activity and uses thereof in the treatment of a disease or condition in which a beneficial clinical effect is achieved by reduction in neuronal nitric oxide synthase (nNOS) activity are provided.

Abstract: The present disclosure relates to compositions and methods of treatment comprising nirogacestat or a pharmaceutically acceptable salt thereof.

Abstract: The disclosure provides methods of treating a patient who has, or who is at risk for developing, systemic immune activation, including cytokine release syndrome (CRS) and sepsis. The method comprises administering a therapeutically effective amount of a compound of Formula I the patient.

Abstract: There is provided tinostamustine or a pharmaceutically acceptable salt thereof for use in the treatment of T-cell prolymphocytic leukemia (T-PLL) in a patient in need thereof.

Abstract: An FGF21 production promoting agent containing, as an active ingredient, a compound represented by the following formula (1): wherein each of R1 and R2, which may be identical to or different from each other, represents, for example, a hydrogen atom; each of R3a, R3b, R4a, and R4b, which may be identical to or different from one another, represents, for example, a hydrogen atom or a halogen atom, or R3a and R3b or R4a and R4b may bond together to form an alkylenedioxy group; X represents an oxygen atom, a sulfur atom, or N—R5 (R5 represents, for example, a hydrogen atom or a C1-4 alkyl group); Y represents, for example, an oxygen atom, an S(O)l group (l is a number of from 0 to 2), or a carbonyl group; Z represents CH or N; n is a number of from 1 to 6; and m is a number from 2 to 6, a salt of the compound, or a solvate of the compound or the salt.

Abstract: An anti-fibrosis pharmaceutical composition and application thereof. The anti-fibrosis pharmaceutical composition specifically comprises: (a) an NRP1 inhibitor and/or an HIF2? inhibitor; and (b) an EPCR pathway activator that promotes the activity of an EPCR pathway. The anti-fibrosis pharmaceutical composition helps reduce organ fibrosis to a certain extent and promotes corresponding organ repair and regeneration.

Abstract: Provided herein is a method for treating a lymphoma in a subject in need thereof, comprising administering to the subject an effective amount of at least one PD-1 pathway agonist.

Abstract: A traditional Chinese drug monomer composition for treating Helicobacter pylori and its preparation method and use thereof, the steps are: a. dissolving drugs: dissolving berberine, evolitrine, and tanshinone I respectively in absolute ethanol; b. combining the drugs: mixing an ethanol solution obtained from the step a according to the mass ratio of berberine, evolitrine, and tanshinone I at 6:1:(0.75-6) to obtain the composition. The present disclosure successfully prepares a traditional Chinese drug monomer composition for the treatment of Helicobacter pylori, which has an extremely obvious inhibitory effect on Helicobacter pylori both in vivo and in vitro, and has a specific effect, low toxicity, and is not easy to produce drug resistance.

Abstract: The present invention generally relates to a method for treating a demyelinating condition, in particular, by administering a combination comprising therapeutically effective amounts of a Rho-associated protein kinase (ROCK) inhibitor, a cyclin-dependent kinase (CDK) inhibitor, and a cyclic adenosine monophosphate (cAMP) activator to a subject in need thereof.

Abstract: A composition and a method for treating tumors. The method includes administering an effective amount of one or more immune checkpoint inhibitors, and an effective amount of a PDE4-selective inhibitor. The composition and the method have a significant anti-tumor effect.

Abstract: This invention relates to the use of (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone (NSI-189) or a pharmaceutically acceptable salt thereof in the treatment of a psychiatric condition in which depressive symptoms are prominent, including major depressive disorder (MIDD), bipolar disorder, post-traumatic stress disorder, substance use disorder, and depression-related aspects of schizophrenia (e.g. negative symptoms) in select patients who exhibit impaired learning and/or memory. The invention also relates to the use of NSI-189 or a pharmaceutically acceptable salt thereof in the treatment of a psychiatric condition in which depressive symptoms are prominent, including major depressive disorder (MDD), in select patients who exhibit impaired learning and/or memory or certain EEG characteristics.

Abstract: The present invention relates to a novel compound as a protein kinase inhibitor, particularly, a RON inhibitor.

Abstract: The present disclosure relates to compounds of Formula (Ia) and (Ib): or a pharmaceutically acceptable salt thereof, which are useful in the treatment of an HIV infection in heavily treatment-experienced patients with multidrug resistant HIV infection.

Abstract: Provided herein are methods of preventing symptomatic ischemic stroke in humans who have suffered from an acute non-cardioembolic ischemic stroke or a high-risk transient ischemic attack.

Abstract: The invention provides new heterocyclic compounds having the general formula (I), or a solvate or a pharmaceutically acceptable salt thereof: wherein R1, R2, R3, R4, R5, R6 and n are as defined herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Abstract: The present invention relates to novel antiviral compounds with specific stereoconfiguration, especially to specific novel enantiomers, to a process for their preparation and to their use as medicaments, in particular as antiviral medicaments.

Abstract: Disclosed herein are compounds and methods of treating diseases and/or conditions associated with FGFR inhibition.

Abstract: The invention concerns a compound of formula (I) R1=H or halogen atom selected in the group consisting of: F, Cl, Br, I, or a pharmaceutically acceptable isomer, salt and/or solvate thereof, for use in preventing and/or treating Kleine-Levin syndrome.

Abstract: The invention relates to compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: Provided herein are methods for treating liver disorders, including non-alcoholic steatohepatitis, and symptoms and manifestations thereof, in a patient which utilize, among others, a combination treatment of an FXR agonist and a THR? agonist.

Abstract: The present disclosure provides an apixaban film product for treatment and prevention of thrombosis and related disorders. Also provided is a method of making the film product. The film product comprises an anticoagulant and a hydrophilic cellulosic polymer.

Abstract: Disclosed is the use of Maraviroc in the preparation of drugs for the treatment of muscle degenerative diseases. Demonstrated herein, for the first time, is the outstanding effect of Maraviroc in treating muscle degenerative diseases, such as muscle inflammation, muscle dystrophy and sarcopenia. The underlying mechanism of such use is also disclosed, which provides a knowledge foundation for such novel and effective treatment strategy.

Abstract: Provided herein are gel, ointment, lotion, or cream formulations including an active pharmaceutical ingredient that includes a tropanyl moiety. The gel, lotion or cream formulations may include at least one low molecular weight (LMW) compound or a pharmaceutically acceptable salt thereof. Also provided herein are gel, ointment, lotion, or cream formulations including an active pharmaceutical agent such as atropine, pilocarpine, physostigmine, or travoprost.

Abstract: The use of montelukast or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of an immunodeficiency disorder and also for the treatment of a disorder characterized by inflammation in a patient that has, or is vulnerable to, a condition characterized by immunosuppression. Particular disorders that may be mentioned include those brought on by radiation therapy as part of e.g. cancer treatment, such as radiation proctitis. Montelukast and salts thereof are preferably administered topically and locally, for example anorectally.

Abstract: This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in an individual in need of such treatment comprising administering to the individual an effective amount of a compound of Formula I.

Abstract: A combination drug for treatment of gastric carcinoma and/or esophagogastric junction cancer, comprising an anti-PD-L1 antibody and anlotinib or a pharmaceutically acceptable salt thereof. The combination drug further comprises at least one third therapeutic agent. In addition, the present application further provides a use of a combination drug or a pharmaceutic composition, which comprises an anti-PD-L1 antibody and anlotinib or a pharmaceutically acceptable salt thereof, in preparation of a drug for treatment of gastric carcinoma and/or esophagogastric junction cancer.

Abstract: In certain embodiments, the present disclosure is directed to methods and uses for treating seizure disorders in a human, wherein the methods and uses comprise orally administering a therapeutically effective amount of the voltage-gated potassium channel allosteric modulator, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (Compound A), to the human in need thereof, for example, under fed conditions. The present disclosure is further directed to various improved methods of therapy and administration of Compound A.

Abstract: In certain embodiments, the present disclosure is directed to methods and uses for treating seizure disorders in a human, wherein the methods and uses comprise orally administering a therapeutically effective amount of the voltage-gated potassium channel allosteric modulator, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (Compound A), to the human in need thereof, for example, under fed conditions. The present disclosure is further directed to various improved methods of therapy and administration of Compound A.

Abstract: The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.

Abstract: Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.

Abstract: Disclosed herein, inter alia, are therapeutic and theragnostic compounds and methods of use thereof.

Abstract: The present invention provides a method of treating depression disease in a treatment resistant patient comprising administering to a mucosal membrane of a patient an effective amount of a pharmaceutically acceptable composition comprising an effective amount of ketamine or dextromethorphan, wherein the mucosal administration of the ketamine or dextromethorphan containing composition allows for the mucosal absorption of the composition eliminating the digestive tract of the patient for effecting a rapid acting antidepressant treatment of the treatment resistant patient. This method includes administering the composition to a patient's mucosal membrane of a respiratory tract, a genitourinary tract, an oral tract, or rectal tract of the patient. A pharmaceutically acceptable composition comprising ketamine or dextromethorphan and a vehicle is disclosed. A biomarker for identifying a depressive disease is set forth.

Abstract: Provided herein are compounds of formula (A?): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X1, X2, X3, X4, Ra, Rb, Rc, L, Q, and Y are as defined herein. Also provided are methods of N inhibiting APOL1 and methods of preparing compounds of formula (A?). Also provided are methods of inhibiting APOL1 and methods of treating an APOL1-mediated disease, disorder, or condition in an individual.

Abstract: The present invention relates to a method of reducing elevated intraocular pressure in humans with open angle glaucoma or ocular hypertension, comprising administering brimonidine or its pharmaceutically acceptable salt. The invention also relates to a pharmaceutical composition suitable for ophthalmic use comprising brimonidine or its pharmaceutically acceptable salt.

Abstract: The disclosure describes extended release solid dosage forms comprising upadacitinib, or a pharmaceutically acceptable salt thereof, wherein the solid dosage form provides pH-independent drug release. In particular, the disclosure describes extended release solid dosage forms comprising upadacitinib, or a pharmaceutically acceptable salt thereof, at least one pH-dependent polymer and at least one release control material.

Abstract: The present invention relates to sitagliptin or a pharmaceutically acceptable salt thereof substantially free from genotoxic impurities particularly nitrosamine impurities and processes for its preparation. In particular, the invention relates to process for the preparation of high purity sitagliptin free from nitrosamine impurities and other genotoxic and carcinogenic impurities below threshold concentration.

Abstract: The present disclosure is directed to methods for treating disease in pediatric patients with the JAK1 selective inhibitor upadacitinib. The diseases and disorders include idiopathic arthritis (pcJIA), systemic juvenile idiopathic arthritis (SJIA), juvenile psoriatic arthritis (JPsA), atopic dermatitis (AD), juvenile ankylosing spondylitis (JAS), juvenile non-radiographic spondyloarthritis (nr-axSpA), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), ulcerative colitis (UC), and Crohn's disease (CD). The treatment methods generally comprise administering to a pediatric patient a therapeutically effective amount of upadacitinib as a stable liquid pharmaceutical composition or a solid dosage form, at a dose based on patient body weight.

Abstract: The present disclosure related to compounds of Formula (I): stereoisomers thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof. The present disclosure also relates to uses of the compounds, including to treat cancer in a subject.

Abstract: The invention relates to a pharmaceutical composition comprising (i) granules comprising Nilotinib, preferably in crystalline form, or a physiologically acceptable salt and/or solvate thereof, preferably crystalline anhydrous Nilotinib hydrochloride or crystalline Nilotinib hydrochloride monohydrate; and (ii) an extragranular phase comprising a surfactant, preferably poloxamer. The granules are preferably dry granulated.

Abstract: The present invention relates to cyclopropylamide compounds that are useful in the treatment of parasitic infestations of fish. The compounds have the formula (I).

Abstract: The present invention relates generally to the use of an ERK1/2 inhibitor in combination with a B-Raf inhibitor that is encorafenib or dabrafenib for treating cancer, specifically solid tumors.

Abstract: Provided are compounds of the Formula (IVB): or pharmaceutically acceptable salts thereof, which are useful for the inhibition of DHX9 and in the treatment of a variety of DHX9 mediated conditions or diseases, such as cancer.

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising the compounds or a pharmaceutically acceptable salts thereof that are useful in methods of preventing pancreatic beta cell degeneration or methods of treating a disorder associated with pancreatic beta cell degeneration, such as type I diabetes.

Abstract: The present invention relates to a lyophilized pharmaceutical composition of hydrolytically unstable pharmaceutical compounds, such as phenobarbital or salts thereof. The present invention also relates to an aqueous solution for injection of phenobarbital or salts thereof that is reconstituted from the lyophilized pharmaceutical composition. The pharmaceutical compositions of the present disclosure have an ethanol content in the range from about 12000 ppm to about 25000 ppm. The composition of the present disclosure, in certain embodiments, is stable following 36 months of storage, wherein the total impurities do not exceed 0.2%. The pharmaceutical compositions of the present disclosure may be used for the treatment of neonatal seizures. The present invention further relates to methods of preparing a lyophilized composition of phenobarbital sodium and to lyophilized pharmaceutical compositions of phenobarbital sodium prepared using the same.

Abstract: The present invention relates to the use of a reduced folate, such as 5-MTHF (5-methyltetrahydrofolate), optionally in combination with tetrahydrobiopterin (BH4) or precursors thereof, for preventing or treating disorders associated with a BH4 deficiency, or low BH4 bioavailability. Such disorders primarily include diseases which have vascular endothelial pathology, or effects on amino acid metabolism or neurotransmission, especially pregnancy related disorders such as pre-eclampsia.

Abstract: Provided herein are the pharmaceutical combination comprising an embryonic ectoderm development (EED) inhibitor and one or more anticancer reagents, and the use of the combination in the treatment of a disease. Provided also is a pharmaceutical composition or a kit comprising the combination.

Abstract: The object of the present invention is to provide a method for treating or preventing diseases related to mitochondrial function by a substance related to the improvement or decrease of mitochondrial function. The above problem can be solved by the agent for promoting formation of mitochondrial respiratory chain supercomplex, comprising Syk inhibitor as an active ingredient. a composition for maintaining or enhancing muscle strength, comprising the agent for promoting formation of mitochondrial respiratory chain supercomplex, or the pharmaceutical composition for treating or preventing muscle hypofunction disease or mitochondrial hypofunction disease, comprising the agent for promoting formation of mitochondrial respiratory chain supercomplex, of the present invention.

Abstract: A drug for treating dry eye, a method for improving wearing experience in populations with contact lens discomfort, and eye drops for treatment.

Abstract: The present invention relates to a PLK1 protein degradation inducing compound, a preparation method thereof, and a use thereof. Compounds of the present invention target PLK1 and BRD4 to degrade PLK1, and decompose BRD4 to a suitable level within the scope of causing no side effects, and thus can be very advantageously used for prevention or treatment of cancer or neural disease.