There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain comprising three complementarity determining regions (CDR1-CDR3) and four framework regions, wherein: (a) at least one lysine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue, and/or (b) at least one arginine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue; wherein the polypeptide has increased intestinal stability relative to a corresponding polypeptide not having said histidine substitutions.

The disclosure provides compounds of Formula (I-A) and (I-B) and the pharmaceutically acceptable salts thereof. The variables, R, R.sup.2, R.sup.3, X.sup.1, X.sup.2, X.sup.3, Y.sup.1, Y, and Z are defined herein. Certain compounds of Formula (I-A) and (I-B) act as selective mitochondrial protonophore uncouplers that do not affect plasma membrane potential. These compounds are useful for treating or decreasing the risk of conditions responsive to mitochondrial uncoupling, such as cancer, obesity, type II diabetes, fatty liver disease, insulin resistance, Parkinson's disease, ischemia reperfusion injury, heart failure, non-alcoholic fatty liver disease (NALFD), and non-alcoholic steatohepatitis (NASH), Because mitochondrial uncouplers decrease the production of reactive oxygen species (ROS), which are known to contribute to age-related cell damage, the compounds are useful for increasing lifespan. Compounds and salts of Formulae (I-A) and (I-B) are also useful for regulating glucose homeostasis or insulin action in a patient. ##STR00001##

The present invention provides Bruton's Tyrosine Kinase (Btk) inhibitor compounds according to Formula (I), or pharmaceutically acceptable salts thereof, Formula (I) or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of Btk inhibitor compounds of Formula I in the treatment of Btk mediated disorders.

##STR00001##

Compositions and methods for the treatment of a disease or disorder are disclosed.

The present invention relates to the technical field of medicinal chemistry, and in particular discloses a 2-oxo-1,2-dihydrobenzo[cd]indole compound and use thereof. The compound and pharmaceutically acceptable salt, isomer, racemate, prodrug, co-crystallized complex, hydrate, and solvate thereof can effectively inhibit the BET bromodomain receptor, and can be used for preparing a medicine for treating cancers, cell proliferative disorders, inflammatory diseases, and autoimmune disorders, sepsis, and viral infections.

This document provides methods and materials involved in assessing mammals (e.g., humans) for arthritis. For example, methods and materials for assessing a mammal's gut microbial diversity to identify the mammal as having arthritis (e.g., rheumatoid arthritis) are provided. This document also provides methods and materials involved in treating arthritis.

Disclosed are compounds of formulae I and II, and pharmaceutically acceptable salts and prodrugs thereof, which are inhibitors of the complement system. Also provided are pharmaceutical compositions comprising such a compound, and methods of using the compounds and compositions in the treatment or prevention of a disease or condition characterized by aberrant complement system activity. ##STR00001##

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) ##STR00001##
or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

Solid forms of Compound (I): ##STR00001##
are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions mediated by BTK activity using the same, and methods for making Compound (I) and solid forms thereof are also disclosed.

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.