Abstract: The present disclosure relates to a stable, reproducible and bioequivalent apixaban compositions, wherein the composition comprising apixaban having a D90 particle size of more than 100 microns, preferably between 300 and 1000 microns, and more preferably between 350 and 800 microns, and further comprising one or more pharmaceutically acceptable excipients. The present disclosure further provides a process for preparation of a pharmaceutical composition comprising apixaban by wet granulation.

Abstract: The present invention provides compounds useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.

Abstract: This document relates to compositions comprising a non-covalently bound complex comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000. This document also relates to compositions comprising cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000. This document also relates to compositions consisting essentially of cabozantinib and human serum albumin, wherein the cabozantinib and the human serum albumin in the composition have a ratio by weight from about 1:5 to about 1:2000.

Abstract: 6-Alkynyl-pyridine of general formula (I) their use as SMAC mimetics, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer.

Abstract: Disclosed is a targeted delivery system for a hydrophobic antitumor drug, referring to conjugates of E-selectin polypeptide ligand-polyethylene glycol-antitumor drug connected by different link bridges containing disulfide bonds. The synthesis of the conjugates, antitumor activity evaluation, the particle size and morphology characteristics of nanoparticles self-assembled by the conjugates in an aqueous solution, and the release of the antitumor drug in different conditions are comprised. The conjugates can actively target at vessels of a tumor site by the E-selectin peptide ligand, and can also self-assemble into nanoparticles in an aqueous solution, so as to be passively targeted at the tumor site by EPR effect.

Abstract: Disclosed herein are inhibitors of the Integrator complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

Abstract: The presently disclosed subject matter provides a solid, immediate release, pharmaceutical multi-particulate dosage form containing at least one population of Opioid Particulates comprising one or more opioids; at least one population of Naloxone Particulates; and a population of Triggering Particulates. Each population of particulates is designed for a specific function to accomplish the desired combination of abuse deterrence and overdose protection.

Abstract: Disclosed are compositions, uses, methods and kits for increasing drug bioavailability in a naltrexone therapy.

Abstract: The present invention provides novel compounds of formula (Ia) that are modulators of RORgamma. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the modulation of RORgamma has therapeutic effects, for instance in autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases, or cholestatic diseases.

Abstract: Disclosed are compounds useful for alteration of NR2F6 activity. In some embodiments of the invention compounds disclosed are utilized for stimulation of NR2F6 activity, alone, or in combination with PKC activation. In other embodiments, the invention teaches use of compounds for inhibition of NR2F6 activation. Stimulation of NR2F6 within the context of the invention is useful, intra alia, for induction of immune inhibition, or stimulation of cellular proliferation without significant induction of differentiation. Inhibition of NR2F6 is desired in situations where the practitioner of the invention seeks to augment immune response, or induce cellular differentiation. In another embodiment, inhibition of NR2F6 expression is desired in situations where inhibition of cancer or cancer stem cells is needed.

Abstract: The disclosure relates to substituted fused heteroaromatic compounds and the use thereof. Specifically, the disclosure provides compounds of the following Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A1-A4, B1-B3, D1-D4 and R1-R3 are defined herein. Compounds having Formula I are kinalse inhibitors. Therefore, compounds of the disclosure may be used to treat clinical conditions caused by DDR functional defects, such as cancer.

Abstract: The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract: The invention relates to 5-amino-2,3-dihydro-1,4-phthalazinedione or related compounds, compositions or combinations thereof, for use in the treatment of chronic progressive multiple sclerosis, in particular primary and secondary progressive multiple sclerosis. The invention in particular relates to the use of 5-amino-2,3-dihydro-1,4-phthalazinedione sodium salt for said purposes.

Abstract: The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.

Abstract: Compositions and methods for the induction of cancer cell death. The compositions and methods of using them include use of compositions in therapy for the treatment of cancer and for the selective induction of apoptosis in cancer cells. The drug combinations described herein can be synergistic and can have lower neurotoxicity effects than the same amounts of other compounds and combinations of compounds and can be effective when a particular cancer has become resistant to previously administered therapies.

Abstract: The present invention encompasses compounds of formula (I), wherein the groups R1 to R7 have the meanings given in the claims and specification, their use as inhibitors of SOS1, pharmaceutical compositions which contain compounds of this kind and their use as medicaments/medical uses, especially as agents for treatment and/or prevention of oncological diseases.

Abstract: The present disclosure is directed to compositions and methods for inhibiting either Toxoplasma gondii (T. gondii) calcium dependent protein kinases (TgCDPKs) or Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the Formula (I), wherein the variables X, Y, Z, R1, and R3 are defined herein.

Abstract: Compounds, pharmaceutical compositions, and methods for reversing fosfomycin resistance are disclosed. Embodiments of the disclosed compounds inhibit fosfomycin-inhibiting enzymes. Some embodiments of the compounds are FosA inhibitors. The disclosed pharmaceutical compositions include (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) a compound, or a pharmaceutically acceptable salt thereof, which inhibits a fosfomycin-inhibiting enzyme. A method of inhibiting growth of a fosfomycin-resistant bacterium includes contacting the bacterium with (i) fosfomycin or a pharmaceutically acceptable salt thereof and (ii) an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof.

Abstract: The application relates to a compound of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of BTK, a pharmaceutical composition comprising a compound of Formula (I), and a method of treating or preventing a disease in which BTK plays a role.

Abstract: Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

Abstract: In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the ?- and ?-isoforms and selective for both ?- and ?-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-? inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Abstract: The present invention relates to a combination treatment which comprises (a) at least one ERK inhibitor preferably Compound B as described herein, and (b) a c-RAF inhibitor or a pharmaceutically acceptable salt thereof, preferably Compound A, which may be combined into a single pharmaceutical composition or prepared for separate or sequential administration. It includes a c-RAF inhibitor and an ERK inhibitor prepared for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly an advanced solid tumor that harbors a Mitogen-activated protein kinase (MAPK) alteration, and includes methods of using these compounds in combination as well as a commercial package comprising such combination.

Abstract: The invention relates to substituted bicyclic compounds, which are useful for inhibition of BET protein function by binding to bromodomains, pharmaceutical compositions comprising these compounds, and use of the compounds and compositions in therapy.

Abstract: Disclosed herein are compounds and methods for antagonizing GPRC6a for the treatment of proteinopathies.

Abstract: The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called “enhancers of IR-mediated cellular cannibalism”. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.

Abstract: Formulations of the HIV compounds atazanavir and cobicistat, and methods of treatment utilizing these formulations, are set forth.

Abstract: Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: wherein R1, is a group of formula (IA): —Ar1-(Alk1)p-(Z)r-(Alk2)s-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C?O)—, —(C?S)—, —SO.sub.

Abstract: The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize Me-porphryin complexs, heme proteins, iron containing molecules, and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

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: The present invention is directed to a novel pharmaceutical formulation comprising 3?-ethynyl-3?-hydroxyandrostan-17-one oxime in an amount of 0.1-10% by weight of the total weight of the composition; and a vehicle comprising (a) 45-100% of a monoester; (b) optionally up to 51% of a diester; and (c) optionally up to about 10% of a triester. Also claimed is a method for the treatment of medical conditions such as hypersomnia and hepathic encephalopathy by the use of a pharmaceutical formulation as claimed.

Abstract: The present invention provides the steroid compound 3beta-hydroxy-5alpha-pregnan-20-one for use in treatment of Tourette's syndrome, obsessive compulsive disorder and/or gambling disorder, as well as methods for treating said disorders and pharmaceutical compositions for use in treatment of said disorders.

Abstract: The invention provides, inter alia, methods of treating a disorder characterized by excessive metakaryotic stem cell growth by a combination metakaryocidal therapy. Also encompassed by the present invention are preventative methods comprising the administration of a metakaryocidal or metakayrostatic therapeutic agent.

Abstract: The present invention is directed to combination therapy comprising metformin or mito-metformin compounds with at least one iron chelating agent for the treatment of cancer and pharmaceutical compositions thereof.

Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Abstract: Sterile pharmaceutical products of Fosaprepitant and a 5-HT3 blocker for parenteral administration including a container containing a formulation of Fosaprepitant or a pharmaceutically acceptable salt thereof and 5-HT3 blocker. The formulations may comprise surface-active agent and a pharmaceutically acceptable vehicle. The formulations may be lyophilized and diluted prior to administration or ready to use liquids or a pre-lyophilization solution.

Abstract: Disclosed are methods, pharmaceutical compositions, kits, and systems for treating or preventing cardiotoxicity in a subject undergoing treatment with an anthracycline chemotherapeutic agent. The methods, pharmaceutical compositions, kits, and systems typically include or utilize an agonist of the retinoic acid receptor gamma (RARG).

Abstract: A pharmaceutical composition and method for regenerating cardiomyocytes in treating or repairing heart muscle damages or injuries caused by an ischemic disease. The pharmaceutical composition contains an active ingredient compound with a backbone structure of Formula (1). The active ingredient compound is capable of (a) increasing viability of myogenic precursor cells to enable said precursor cells to survive through an absolute ischemic period; (b) reconstituting a damaged blood supply network in said heart region where said injured muscle is located; and (c) enhancing cardiomyogenic differentiation efficiency of said precursor cells down cardiac linage, said steps being performed simultaneously or in any particular order.

Abstract: The present invention relates to a new class of steroid saponins that have interesting biological activity. In particular the present invention relates to a class of steroid saponins in which the sugar moiety has been selectively functionalised to introduce a moiety that contains either, (i) a hydrogen ion donor, (ii) a hydrogen ion acceptor or (iii) a combination thereof. These new, water-soluble compounds are found to not only have potent anti-cancer properties per se but also have the ability to promote the immune response in a subject and can thus act as adjuvants for T-cell activation in cancer therapy.

Abstract: A pharmaceutical composition of Capecitabine, wherein the composition includes immediate release Capecitabine and extended release Capecitabine. Further disclosed is a process for the preparation of the composition.

Abstract: Disclosed herein are new cyclic dinucleotide compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulation of immune response to disease, and induce Stimulator of Interferon Genes (STING) dependent type I interferon production and co-regulated genes in a human or animal subject are also provided for the treatment diseases such as cancer, particularly metastatic solid tumors and lymphomas, inflammation, allergic and autoimmune disease, infectious disease, and for use as anti-viral agents and vaccine adjuvants.

Abstract: Provided is a method of preventing and treating a dry eye syndrome comprising administering a pharmaceutical composition comprising sulglycotide or its pharmaceutically acceptable salt as an active ingredient.

Abstract: The present disclosure describes compositions comprising ?-lactam antibiotics and branched polyethylenimines (BPEI), having efficacy against various Gram-positive bacteria, for example Gram-positive bacteria having resistance against ?-lactam antibiotics, one non-limiting example of which is Methicillin-resistant Staphylococcus aureus (MRSA). The compositions result in the resensitization of such resistant bacterial strains to traditional antibiotic therapies such as ?-lactam antibiotics.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: The invention is generally directed to a method of enhancing proliferation of T regulatory cells (Tregs) in vitro, comprising contacting Tregs with cells (I), or conditioned medium from the cells, in the presence of one or more Treg stimulation agents. The Treg stimulation agent(s) is present in an amount and for a time effective to stimulate proliferation of the Tregs. The cells (I) are present in an amount and for a time effective to enhance proliferation of the Tregs. The cells (I) are non-embryonic stem, non-germ cells characterized by one or more of the following: extended replication in culture and express markers of extended replication, express markers of pluripotentiality, and have broad differentiation potential, are not tumorigenic or transformed, and have a normal karyotype. The invention is also directed to methods for immune modulation using the proliferated Tregs, cell banks, drug discovery methods, populations, and compositions of the proliferated Tregs.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: Provided herein are methods of modulating, in vivo, cells engineered with a recombinant receptor, such as a T cell receptor (TCR) or chimeric antigen receptor (CAR). In some embodiments, the methods include disrupting an area in the subject in which the cells are present or likely to be present or were present or were likely to be present, such as a lesion, including a tumor. In some embodiments, the disruption alters the environment of the lesion, e.g. tumor microenvironment. In some embodiments, the disruption is a biopsy. In some aspects, the provided methods result in increased expansion, and, in some cases, a more robust and durable response, of the engineered cells after carrying out the disruption.

Abstract: The present invention relates to cancer immunotherapy. In particular, provided herein are compositions and methods for improving the efficacy of cell therapies cancer and other diseases.

Abstract: Provided herein are compositions including compounds and/or cells for treating a disease associated with Group 2 innate lymphoid cells (ILC2s), and methods of treatment.