Related Experiment Video
Updated: Feb 2, 2026
12:27
A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
4.0K
An update on sphingosine-1-phosphate receptor 1 modulators.
Alexander Marciniak1, Sara M Camp2, Joe G N Garcia2
1Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ 85721, United States.
Bioorganic & Medicinal Chemistry Letters
|November 10, 2018
Summary
This review explores synthetic sphingolipids targeting the sphingosine-1-phosphate receptor 1 (S1P1) for autoimmune diseases. It highlights fingolimod and newer S1P1 agonists for potential therapies.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Sphingolipids are crucial lipids in eukaryotes, regulating cellular signaling.
- Sphingosine-1-phosphate receptor 1 (S1P1) is implicated in autoimmune diseases like asthma and multiple sclerosis (MS).
Purpose of the Study:
- To review sphingolipid metabolism and S1P1 mechanisms.
- To provide an overview of synthetic S1P1 agonists for autoimmune disorders.
Main Methods:
- Literature review of sphingolipid metabolism.
- Analysis of S1P1 receptor signaling pathways.
- Overview of synthetic sphingosine analogs and their properties.
Main Results:
- FTY720 (fingolimod) is an oral therapy for MS, acting as a prodrug.
- Structural analogs of fingolimod have been developed for improved therapeutic profiles.
- Synthetic S1P1 agonists offer potential for autoimmune disease management.
Conclusions:
- Targeting S1P1 with synthetic sphingolipids is a promising strategy for autoimmune diseases.
- Ongoing research focuses on optimizing stability, bioavailability, and efficacy of these agents.
Related Concept Videos
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
622
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
622
02:15SN1 Reaction: Stereochemistry
10.3K
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
10.3K
02:05SN1 Reaction: Kinetics
9.6K
In an SN2 reaction, the reaction rate depends on both the type of nucleophile and the substrate. A hindered tertiary alkyl halide is practically inert to the SN2 mechanism despite using a strong nucleophile.
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
9.6K
02:25SN1 Reaction: Mechanism
14.3K
Kinetic studies of ionization of a tertiary halide in a protic solvent suggest that only the substrate participates in the rate-determining step (slow step). The nucleophile is involved only after the slowest step. The SN1 reaction takes place in a multiple-step mechanism.
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
14.3K
02:42Acidity of 1-Alkynes
11.2K
The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
11.2K
02:27Predicting Products: SN1 vs. SN2
17.3K
Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
With increased substitution on the alkyl halide,...
17.3K