Abstract: Provided herein, in some embodiments, are nucleic acid-based tools that may be used for high-throughput functional genomics studies as well as for the generation of knockout (gene inactivation or deletion) or knockin (gene activation or insertion) cell lines. Tools of the present disclosure include an “activatable reporter cassette,” a guide RNA construct and a nuclease that can be used together, for example, to modify and isolate targeted cells of interest.

Abstract: The invention relates to novel heteroaryl compounds of Formula (I) and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cardiovascular diseases, and methods treating sepsis or septic shock, using the novel heterocyclic compounds disclosed herein.

Abstract: The invention relates to a novel group of compounds of Formula (I) or salts thereof: wherein Y, Z1, Z2, R1, R4, R5 and n are as described in the specification, which may be useful in the treatment or prevention of a disease or medical condition mediated through protein kinase B (PKB) such as cancer. The invention also relates to pharmaceutical compositions comprising said compounds, methods of treatment of diseases mediated by PKB using said compounds and methods for preparing compounds of Formula (I).

Abstract: An improved chemical process for the manufacture of the compound of Formula (I), which is useful, for example, as a late-stage chemical intermediate in the production of osimertinib (AZD9291) and pharmaceutically acceptable salts thereof.

Abstract: The present application relates to novel compounds of formula (I) to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to the spike protein of SARS-CoV-2 and methods of making and selecting the same. The antibodies can be used, for example, in prophylaxis, post-exposure prophylaxis, or treatment of SARS-CoV-2 infection. The antibodies can also be used to detect SARS-CoV-2 infection in subject.

Abstract: Methods comprising repeating cycles of administration of a composition comprising cediranib according to a fixed intermittent dosing regimen comprising administration of an effective amount of the composition comprising cediranib on one or more consecutive days of a cycle followed by one or more consecutive days of rest on which said composition is not administered are disclosed herein, and may be used as monotherapy or may comprise administration of one or more partner drugs or therapies and may be used in combination therapy.

Abstract: The present disclosure relates to salts of compounds of Formula (I) prepared as a xinafoate (1-hydroxy-2-naphthoate) salt (Formula (Ia)), pharmaceutically acceptable compositions comprising same and methods of using the same.

Abstract: Disclosed are intermediates and methods of synthesizing Compound 1.

Abstract: The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1 and R2 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.

Abstract: The present disclosure relates to certain (2S)—N-[(1S)-1-cyano-2-phenylethyl]-1,4-oxazepane-2-carboxamide compounds (including pharmaceutically acceptable salts thereof), that inhibit dipeptidyl peptidase 1 (DPP1) activity, to their utility in treating and/or preventing clinical conditions including respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), to their use in therapy, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: A method is provided for lowering blood pressure in a subject in need thereof by administering an angiotensin II receptor blocker pharmaceutical composition to a subject qualified for over-the-counter access to the angiotensin II receptor blocker pharmaceutical composition. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition includes azilsartan medoxomil, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan. In some embodiments, the angiotensin II receptor blocker pharmaceutical composition comprises an active ingredient that is (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2?-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: The invention concerns compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 have any of the meanings hereinbefore defined in the description; process for their preparation, pharmaceutical compositions containing them and their use in treating KIT mediated diseases.

Abstract: The specification relates to compounds of Formula (I): and to pharmaceutically acceptable salts thereof, to processes and intermediates used for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of cell proliferative disorders.

Abstract: The present specification provides a compound of formula (I): or a pharmaceutically acceptable salt thereof; a process for preparing such a compound; and to the use of such a compound in the treatment of an ROR? and/or ROR?t mediated disease state.

Abstract: A score of a histopathological diagnosis of cancer is generated by loading an image patch of an image into a processing unit, determining how many pixels of the image patch belong to a first tissue, processing additional image patches cropped from the image to determine how many pixels of each image patch belong to the first tissue, computing the score and displaying it along with the image on a graphical user interface. The image patch is cropped from the image of a slice of tissue that has been immunohistochemically stained using a diagnostic antibody. The first tissue comprises tumor epithelial cells that are positively stained by the diagnostic antibody. Determining how many pixels belong to the first tissue is performed by processing the image patch using a convolutional neural network. The score of the histopathological diagnosis is computed based on the total number of pixels belonging to the first tissue.

Abstract: Systems and methods are provided for over the counter statin delivery to a subject. Survey results from the subject are run against a first plurality of filters. When a filter in the first plurality of filters is fired, the subject is deemed not qualified. The survey results are also run against a second plurality of filters. When a respective filter in the second plurality is fired, the subject is provided with a corresponding warning. The method proceeds to a fulfillment process when no filter in the first plurality fires and the subject has acknowledged each warning associated with each fired filter in the second plurality. The fulfillment stores the composition order, communicates a drug facts label for the statin to the subject, and authorizes, upon subject confirmation that the label has been read, provision of the statin to the subject, the authorization including a destination associated with the subject.

Abstract: The present application relates to novel compounds of formula (I) to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.

Abstract: There are disclosed certain 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-one compounds of formula (I), and pharmaceutically acceptable salts thereof, together with compositions containing them and their use in therapy. The compounds are inhibitors of the enzyme MPO and are thereby particularly useful in the treatment or prophylaxis of cardiovascular disorders such as heart failure and coronary artery disease related conditions.