Summary The sphingosine 1-phosphate (S1P) signalling pathways have important and
diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for
various diseases due to their involvement in regulation of lymphocyte trafficking, brain and
cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators
were first developed to prevent rejection by the immune system following renal
transplantation, but the only currently approved indication is multiple sclerosis. The primary …

Abstract Sphingosine 1-phosphate (S1P) receptor modulators possess a unique mechanism
of action as disease-modifying therapy for multiple sclerosis (MS). Subtype 1 S1P receptors
are expressed on the surfaces of lymphocytes and are important in regulating egression
from lymph nodes. The S1P receptor modulators indirectly antagonize the receptor's function
and sequester lymphocytes in lymph nodes. Fingolimod was the first S1P agent approved in
the USA in 2010 for relapsing MS after two phase III trials (FREEDOMS and TRANSFORMS) …