Abstract: The present invention relates to fibronectin based scaffold domain proteins that bind PCSK9. The invention also relates to the use of the innovative proteins in therapeutic applications to treat atherosclerosis, hypercholesterolemia and other cholesterol related diseases. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative protein.

Abstract: The present disclosure generally relates to compounds of formula (I), wherein R2 is a phenyl or pyridinyl moiety, useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

Abstract: Disclosed are imidazole and thiazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, A, Z, R1 and R? are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-?, and can be used to treat disease by blocking TGF-? signaling.

Abstract: The present invention provides compounds of Formula (I): wherein A, Y and R1 are each as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

Abstract: Compounds of Formula I, including their salts, as well as compositions and methods of using the compounds are set forth. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV: formula (I).

Abstract: Benzodiazepine dimers having a structure represented by wherein X comprises a heteroaromatic moiety and is as further defined in the application; R1 is and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used in an antibody-drug conjugate (ADC).

Abstract: The present invention provides compounds of Formula (I) or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, 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: A process is provided for preparing 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates used in the process. The compound is a 11-beta hydroxysteroid dehydrogenase type I inhibitor which exhibits activity in the treatment of various metabolic diseases.

Abstract: The present disclosure is generally directed to compounds of formula (I) which can inhibit AAKI (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAKI.

Abstract: The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

Abstract: Compounds of Formula I are provided, including pharmaceutically acceptable salts thereof: wherein A is selected from the group consisting of: wherein Z is selected from the group consisting of: which are useful as HIV attachment inhibitors.

Abstract: Disclosed are heteroaryl compounds of Formula (I), (I), or pharmaceutically acceptable salts thereof, wherein Z is CH or N; W is CR3 or N; and R1, R2, and R3 are defined herein. Also disclosed are methods of using such compounds in the treatment of at least one CYP17 associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.

Abstract: Disclosed are compounds of Formula (I), wherein: X is O or —NR3; R1 is —CH2CH2CH3, —CH2CF3, —CH2CH2CF3, —CH2CF2CH3, —CH2CH2CH2CF3, —CH2CH2CF2CH3, —CH2CH(CH3)CF3, —CH2CH2CH2F, or CH2(cyclopropyl); R2 is —CH2CH2CH3, —CH2CF3, —CH2CH2CF3, —CH2CF2CH3, —CH2CH2CH2CF3, —CH2CH2CH2F, —CH2CH(CH3)CF3, CH2CH2CF2CH3, —CH2(cyclopropyl), —CH(CH3)(cyclopropyl), phenyl, fluorophenyl, chlorophenyl, trifluorophenyl, methylisoxazolyl, pyridinyl, formula (i), formula (ii), formula (iii), formula (iv) or formula (v); Ring A is phenyl or pyridinyl; and R3, Ra, Rb, Rc, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

Abstract: Disclosed are azaindazole compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein: Q is: (i) 5-membered heteroaryl comprising at least one nitrogen heteroatom and substituted with zero to 2 Rg; or (ii) 9- to 10-membered bicyclic heteroaryl selected from Formula (II) and; wherein Ring A is a 5- to 6-membered aryl or heteroaryl fused ring substituted with zero to 2 Rg; and R1, R2, R3, and Rg are defined herein. Also disclosed are methods of using such compounds in the treatment of at least one CYP17 associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.

Abstract: A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate. A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.

Abstract: The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4—P-M-M4??I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: Disclosed are compounds of Formula (I) or pharmaceutically acceptable salts thereof, wherein Q is R1 is cycloalkyl, heteroaryl, or heterocyclyl, each optionally substituted with one to five substituents independently selected from C1 to C6 alkyl, C1 to C4 haloalkyl, —OR4, and/or halogen; and R2, R3, R4, and n are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as vascular disease and autoimmune diseases.

Abstract: The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating disorders associated with an excess or imbalance of tachykinins or serotonin or both.

Abstract: The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.