Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, 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 autoimmune diseases and vascular disease.

Provided herein are compounds and pharmaceutical compositions thereof for treating a birthmark in a subject in need thereof, wherein the compound is according to any one of formula (I), (II), (III), (IV), and (V). wherein, X.sup.1, X.sup.2, X.sup.3, R.sup.1, R.sup.2, R.sup.2a, R.sup.13, R.sup.13a, R.sup.23, R.sup.23a, R.sup.23b, R.sup.33, R.sup.33a, R.sup.33b, R.sup.43, R.sup.43a, R.sup.51, R.sup.53, R.sup.53a, R.sup.53b, bond “a”, and subscript n are described herein.

Provided herein are compositions comprising a vaccine composition and an agent that triggers metabolic reprogramming of B cells and methods of using the agent that triggers metabolic reprogramming of B cells to increase effectiveness of the vaccine by increasing memory B cell population. One aspect of the disclosure includes a method of increasing the effectiveness of a vaccine in a subject, which comprises administering a B cell metabolic reprogramming agent to the subject in a dose and schedule configured to increase the effectiveness of the vaccine, wherein the subject is administered with the vaccine.

Provided herein are compositions comprising a vaccine composition and an agent that triggers metabolic reprogramming of B cells and methods of using the agent that triggers metabolic reprogramming of B cells to increase effectiveness of the vaccine by increasing memory B cell population. One aspect of the disclosure includes a method of increasing the effectiveness of a vaccine in a subject, which comprises administering a B cell metabolic reprogramming agent to the subject in a dose and schedule configured to increase the effectiveness of the vaccine, wherein the subject is administered with the vaccine.

Provided herein are compositions comprising a vaccine composition and an agent that triggers metabolic reprogramming of B cells and methods of using the agent that triggers metabolic reprogramming of B cells to increase effectiveness of the vaccine by increasing memory B cell population. One aspect of the disclosure includes a method of increasing the effectiveness of a vaccine in a subject, which comprises administering a B cell metabolic reprogramming agent to the subject in a dose and schedule configured to increase the effectiveness of the vaccine, wherein the subject is administered with the vaccine.

The present invention relates to the role of purinergic receptors and ATP in T cell activation and autocrine system signaling. In one embodiment, the present invention provides a method of preventing or treating diabetes by administering a therapeutically effective inhibitor of ATP to a subject. In another embodiment, the present invention provides a method of preventing or treating fibrosis by administering a P2X7R soluble fusion protein. In another embodiment, the present invention provides a method of preventing or treating graft rejection by administering an inhibitor of P2X receptor signaling.

The present invention relates to the role of purinergic receptors and ATP in T cell activation and autocrine system signaling. In one embodiment, the present invention provides a method of preventing or treating diabetes by administering a therapeutically effective inhibitor of ATP to a subject. In another embodiment, the present invention provides a method of preventing or treating fibrosis by administering a P2X7R soluble fusion protein. In another embodiment, the present invention provides a method of preventing or treating graft rejection by administering an inhibitor of P2X receptor signaling.

A compound represented by Formula (1) can be used as a prolonged ectoparasite-controlling agent for an animal. A preparation for systemic application for use in prolonged control of an ectoparasite in an animal include the compound. A method for prolonged control of an ectoparasite on an animal includes systemically applying the compound. The compound may be used for preparing a medicament for prolonged control of an ectoparasite on an animal. A horticultural or agricultural insecticide containing the compound, and a method of protecting a crop from a harmful organism is also provided. ##STR00001##

A compound represented by Formula (1) can be used as a prolonged ectoparasite-controlling agent for an animal. A preparation for systemic application for use in prolonged control of an ectoparasite in an animal include the compound. A method for prolonged control of an ectoparasite on an animal includes systemically applying the compound. The compound may be used for preparing a medicament for prolonged control of an ectoparasite on an animal. A horticultural or agricultural insecticide containing the compound, and a method of protecting a crop from a harmful organism is also provided. ##STR00001##

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.