Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA ? 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Abstract: The present invention relates to compositions and methods of inducing the self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair cells.

Abstract: The present disclosure relates generally to compounds of formula (I) or a pharmaceutically acceptable salt, prodrug, deuterated analog, tautomer, stereoisomer, or mixture of stereoisomers thereof and their use as LRRK2 inhibitors.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically-acceptable salt thereof, that is an inhibitor of JAK kinases. The invention also provides pharmaceutical compositions comprising such compound, a crystalline form, methods of using such compound to treat inflammatory skin diseases and other diseases, and processes and intermediates useful for preparing such compound.

Abstract: The present invention discloses a substituted pyridine compound represented by formula I, and a pharmaceutically acceptable salt, stereoisomer and tautomer thereof. The compounds of the present invention are useful in the treatment of cancers.

Abstract: Compositions and methods for inducing pterygium regression from visual axis/central cornea, stabilizing pterygium, treating hyperemia and symptoms in pterygium patients, and treating pterygium recurrence following pterygiectomy are disclosed. The methods include administration of a multikinase inhibitor, an antimetabolite or a combination thereof to patients in need thereof.

Abstract: Provided are: a protein degradation inducing tag which is a molecule that has affinity with proteases and does not inhibit degradation of a protein by proteases; a protein degradation inducing molecule that is a conjugate of at least one protein degradation inducing tag and at least one protein binding molecule that binds to a protein; and a usage of those.

Abstract: Provided are compositions comprising Compound I having the following structure: or a pharmaceutically acceptable salt thereof, and a solubilizing agent; methods of making the same; and methods of using the same.

Abstract: Bicyclic dihydropyrimidine-carboxamide compounds of formula I described herein inhibit Rho Kinase and may be used for the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

Abstract: The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) TBK1. In particular, the present invention is directed to compounds, which contain on one end an E3 ubiquitin ligase binding moiety which binds to an E3 ubiquitin ligase and on the other end a moiety which binds TBK1 such that TBK1 is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of TBK1. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of TBK1.

Abstract: Amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate are provided, as well as pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions may be orally administered to a patient in either the fed or fasted state, with a decrease or elimination of the food effect. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (e.g., Cmax, AUC0-t and/or AUC0-infinity) of nilotinib, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.

Abstract: The present invention provides, in certain embodiments, compositions comprising a uniform population of free, single crystals of a hydrophobic compound. Methods of administering, and processes for preparing, compositions comprising a uniform population of free, single crystals of a hydrophobic compound are also provided.

Abstract: The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I or Formula II, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds X1, X2, X3, X4, X5, Y1, Y2, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are as defined in the specification. The inventive Formula I and Formula II compounds are inhibitors of Mnk and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically-acceptable salt thereof, that is an inhibitor of JAK kinases. The invention also provides pharmaceutical compositions comprising such compound, a crystalline form, methods of using such compound to treat inflammatory skin diseases and other diseases, and processes and intermediates useful for preparing such compound.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: X-A-Y—Z-L-R1??(I) which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The present invention is relates to an improved process for the preparation of pazopanib or a pharmaceutically acceptable salts thereof. The present invention also relates to novel polymorphic Forms of pazopanib hydrochloride, and its intermediates thereof.

Abstract: The invention relates to combinations comprising an HDAC inhibitor and a Her2 inhibitor for the treatment of breast cancer in a subject in need thereof. The invention also relates to combinations comprising an HDAC inhibitor and a PI3K inhibitor for the treatment of breast cancer in a subject in need thereof. Also provided herein are methods for treating breast cancer in a subject in need thereof comprising administering to the subject an effective amount of one of the above combinations. Further provided are methods for inhibiting migration and/or invasion of a breast cancer cell in a subject by administering to the subject a HDAC6 specific inhibitor.

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.

Abstract: Compounds within the scope of the present invention have a Formula 1 or a salt or prodrug thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R2 and R3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC50 of from 0.003 ?M to 3.7 ?M; a TAK1 IC50 of from 0.008 ?M to 132 ?M; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

Abstract: The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, and R7 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat a condition or disorder responsive to inhibition of ALK such as cancer.

Abstract: The present invention provides an EGFR kinase inhibitor and a preparation method and use thereof. Specifically, the present invention provides a compound as shown in formula (I), the definition of each group therein being as described in the description. Said compound is an efficient EGFR inhibitor.

Abstract: The present disclosure provides combination therapy of a transcription inhibitor and a kinase inhibitor. The combination of the transcription inhibitor and the kinase inhibitor may be useful in treating and/or preventing in a subject a proliferative disease, such as proliferative a disease that is resistant to the transcription inhibitor alone or the kinase inhibitor alone. In certain embodiments, the proliferative disease is a cancer. The combination of the transcription inhibitor and the kinase inhibitor is expected to be synergistic.

Abstract: Provided in the present invention are a compound having the effects of preventing and treating diseases related to IDH mutation, and a preparation method and use thereof.

Abstract: The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

Abstract: The present invention relates to compounds represented by Formula 1 or a pharmaceutically acceptable salt thereof, wherein: R1 is chloro or methyl; R2 is hydrogen or chloro; R3 is hydrogen, fluoro, chloro, bromo, methyl, ethyl, isopropyl, pentyl, hexyl, octyl, methoxy, phenoxy, (4-nitrophenyl)sulfonyl, piperidin-4-yl, or piperazin-1-yl; R4 is hydrogen, chloro, methyl or trifluoromethyl, phenoxy, (4-nitrophenyl)sulfonyl or piperidin-4-yl; or R3 and R4, together with the carbons to which they are attached, form a fused ring selected form the group consisting of: n is 1 or 2. These compounds according to the present invention remarkably inhibits activity of DRAK that inhibits signal systems of TGF-?, which is known to suppress cancer growth, and thus the novel pyrimidine compounds can be used as a pharmaceutical composition for preventing or treating cancer and can be used as a pharmaceutical composition for preventing or treating inflammatory disease.

Abstract: The present invention provides a compound of the formula (1): wherein X, R1, R2, R3, R4, R5, R6, Y1, Y2, L, and m are as defined in the description, and a pharmaceutically acceptable salt thereof, which are useful as a vaccine adjuvant.

Abstract: The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.

Abstract: This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminosterol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias, or derivatives thereof, to a subject in need.

Abstract: The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

Abstract: The present invention relates to compounds of general formula (I). wherein A represents an optionally substituted heterocycle group, B represents an aryl or heteroaryl group and wherein X, R1, R2, R3, R4 and R5 are as defined in the description. Compounds of formula (I) are useful to destroy, inhibit, or prevent the growth or spread of cells, especially malignant cells, into surrounding tissues implicated in a variety of human and animal diseases.

Abstract: The invention provides a compound of formula (I): or a pharmaceutically-acceptable salt thereof, that is an inhibitor of JAK kinases. The invention also provides pharmaceutical compositions comprising such compound, a crystalline form, methods of using such compound to treat inflammatory skin diseases and other diseases, and processes and intermediates useful for preparing such compound.

Abstract: This disclosure relates to the use of kinase inhibitor to treat or prevent infectious diseases such as tuberculosis. In certain embodiments, this disclosure relates to treating or preventing an infectious disease comprising administering an effective amount of a kinase inhibitor or other compound disclosed herein to a subject in need thereof. In certain embodiments, the disclosure relates to methods of treating or preventing tuberculosis comprising administering a kinase inhibitor to a subject in need thereof. In certain embodiments, the subject is diagnosed with Mycobacterium tuberculosis (Mtb) that is resistant to multiple antibiotic agents.

Abstract: Use of prostacyclin or an analogue thereof for treatment of a new medical indication in acute critically ill patients, in particular acute critically ill patients with systemic endothelial damage, a biomarker for identifying individuals that have a new medical indication, and a method for identifying a new medical indication.

Abstract: The present invention relates to novel compounds of formula (I) as GPR119 agonist, composition compositions containing such compounds and method of preparation thereof.

Abstract: The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

Abstract: The present disclosure relates to compounds having the Formula (Formula (I)) which are inhibitors of STAT5.

Abstract: 4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 4-azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Abstract: Tyrosine amide compounds of formula I described herein inhibit Rho Kinase and may be used for the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

Abstract: Disclosed area fused ring pyrimidine compound, and an intermediate, a preparation method, a composition and a use thereof. The fused ring pyrimidine compound is a compound as shown in formula I, a tautomer, an enantiomer, a diastereoisomer, a pharmaceutically acceptable salt, a metabolite, a metabolic precursor or a prodrug thereof, wherein the above-mentioned compound is used for the preparation of a medicine for preventing, remitting or treating one or more of immune system diseases, autoimmune diseases, cell proliferative diseases, allergic disorders and cardiovascular diseases, and the compound has a strong inhibitory effect on the Janues kinase, FGFR kinase, FLT3 kinase and Src family kinase.

Abstract: A novel class of inhibitors of protein kinases that are useful in the treatment of cell proliferative diseases and conditions, and especially those characterised by over-expression of CDK4, CDK6 and/or cyclin D, including certain cancers of lung, breast, brain, central nervous system, colorectal cancer and leukaemias.

Abstract: The present disclosure relates to a 2,4-disubstituted pyrimidine derivative and the use thereof as a therapeutically effective cyclin-dependent kinase (CDK) inhibitor. In particular, the present disclosure relates to the use of a new 2,4-disubstituted pyrimidine derivatives shown in formula (I) and a pharmaceutical composition thereof as a selective CDK4/6 inhibitor in preventing or treating diseases related to CDK4/6.

Abstract: The disclosure includes a method of inducing direct reprogramming (transdifferentiation) into non-oncogenic cells accompanied by tumor cell apoptosis in human tumor cells using a small molecule composition, based on the mechanism of chemical-induction of direct cellular reprogramming. The disclosure also includes a small molecule composition used for the method, and culture media and agents prepared from the composition.

Abstract: The present invention relates to novel geminal substituted aminobenzisoxazole compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of ?7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.

Abstract: The current invention is directed to a class of compounds that inhibit the function of Thymidylate synthase. Thymidylate synthase inhibition was noted to result in inhibition of tumor cell grow and killing of tumor cells. Thymidylate synthase inhibition is, thus, useful for treatment of various types of cancers, including but not limited to, acute lymphoblatic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute monocytic leukemia (AMOL), hairy cell leukemia, large cell immunoblastic lymphoma, plasmacytoma, multiple myeloma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, brain cancer, lung cancer, central nervous system (CNS) cancer, melanoma, renal cancer, prostate cancer, colon cancer, ovarian cancer and breast cancer. The compounds disclosed herein can be used alone or in combination with other cancer treatment regimens (e.g.

Abstract: The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.

Abstract: The invention provides compounds of Formula I, and methods of treating or preventing a bacterial infection in a subject using a compound of Formula I. The invention also provides the use of a compound of Formula I in the manufacture of a medicament for the treatment of a bacterial infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a bacterial infection in a subject and to a medical device comprising the composition of the invention.

Abstract: Disclosed herein is a long acting pharmaceutical composition for treating or preventing human immunodeficiency virus (HIV) infection. The pharmaceutical composition comprises a suspension of a lysine-based aspartyl protease inhibitor or salt thereof, a surface modifier, and a pharmaceutically acceptable carrier; wherein the lysine-based aspartyl protease inhibitor or salt thereof has an average effective particle size of less than about 500 nm. A method for treating or preventing HIV infection with the pharmaceutical composition is also disclosed.

Abstract: The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.

Abstract: There are disclosed aminopyrimidinecarboxamide compounds useful as pharmaceutical agents, synthesis processes, and pharmaceutical compositions which include aminopyrimidinecarboxamides compounds. More specifically, there is disclosed a genus of CXCR2 inhibitor compounds that are useful for treating a variety of inflammatory and neoplastic disorders.