LPL Receptor Modulator

Fingolimod (FTY720) hydrochloride is a sphingosine 1-phosphate (S1P) antagonist with IC₅₀ of 0.033 nM in K562 and NK cells. Fingolimod hydrochloride is also a pak1 activator and immunosuppressant.

VPC 23019, an aryl amide-containing Sphingosine 1-phosphate (S1P) analog, is a competitive antagonist at the S1P1 and S1P3 receptors (pK_i= 7.86 and 5.93, respectively) and an agonist at the S1P4 and S1P5 receptors (pEC₅₀= 6.58 and 7.07, respectively).

Ozanimod (RPC-1063) hydrochloride, a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P receptor subtypes 1 (S1P1) and 5 (S1P5). Ozanimod hydrochloride has modulate effect for hS1P₁ and hS1P₅ receptor with EC₅₀s of 1.03 nM and 8.6 nM, respectively. Ozanimod hydrochloride can be used for the research of relapsing multiple sclerosis (MS) .

Mocravimod (KRP-203 free base) is a sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod preferentially binds to S1PR1 over S1PR2 and S1PR3 in cardiomyocytes. Mocravimod significantly lowered the concentration of reactive oxygen species (ROS), prevented mitochondrial permeability transition pore opening, boosted mitochondrial membrane potential (MMP), and increased phosphorylation of AKT, EKR, GSK-3β, JAK2, and STAT3. Mocravimod retains T cell effector function. Mocravimod can be used for the study of acute myelogenous leukemia, diabetes and Myocardial Ischemia-Reperfusion Injury (MIRI).

Amiselimod (MT-1303) is converted to its active metabolite Amiselimod phosphate by sphingosine kinases in vivo. Amiselimod is an orally active and high selectivity sphingosine 1-phosphate receptor-1 (S1P1) agonist, designed to reduce the bradycardia effects associated with fingolimod and other S1P receptor modulators. Amiselimod inhibits chronic colitis via inhibiting infiltration of colitogenic Th1 and Th17 cells into the colon. Amiselimod inhibits lupus nephritis by reducing the infiltration of autoreactive T cells into the kidneys. Amiselimodis promising for research of autoimmune diseases.

Tamuzimod is a potent immunomodulator. Tamuzimod has S1P Receptor modulatory activity with an EC₅₀ of <1 μM.

Etrasimod arginine is an orally available S1P receptor modulator that is a potent full agonist of the S1P1 receptor and has partial agonist activity at S1P4. Etrasimod arginine reduces inflammation in a CD4⁺CD45RB^high T cell-transferred mouse colitis model.

Decyl phosphate is a selective LPA₂ agonist (EC₅₀: 1.8 μM) and LPA₁/LPA₃ antagonist. Decyl phosphate can be used in the research of blood disorders.

S1P1 agonist 4 has a better profile in both potency (EC₅₀ < 0.05 mg/kg) and predicted human half-life (t1/2 ∼ 5 days).

N-PTyrosine PA (N-Palmitoyl-tyrosine phosphoric acid) ammonium is a lysophosphatidic acid (LPA) receptor modulator, which exhibits weak inhibitory activity against LPA1 and partial agonist properties towards LPA5. N-PTyrosine PA ammonium inhibits the activation of LPA receptors and downstream responses by competing with agonists for binding sites. N-PTyrosine PA ammonium can induce morphological changes and aggregation, and also inhibit LPA-induced morphological changes through receptor desensitization caused by pre-incubation. N-PTyrosine PA ammonium can be used in the research of related diseases such as atherosclerosis and acute ischemic syndromes (e.g., unstable angina, myocardial infarction, stroke).

Udifitimod (BMS-986166) is a potent, selective and orally active S1P1R modulator. Udifitimod has the potential for the research of autoimmune diseases.

GSK1842799, an alkyl-substituted biaryl amino alcohol, is a selective S1P1 modulator developed for multiple sclerosis (MS). Upon phosphorylation, GSK1842799-P exhibited subnanomolar S1P1 agonist activity with over 1000-fold selectivity over S1P3. The compound showed good oral bioavailability, rapid in vivo conversion to GSK1842799-P, and significant lymphocyte count reduction at 0.1 mg/kg. It matched FTY720 efficacy at 3 mg/kg in the mouse EAE model and achieved comparable plasma levels to FTY-720 phosphate in cynomolgus monkeys. With favorable ADME, PK/PD properties, and toxicology, GSK1842799 advanced to further clinical development.

BMS-986104 is a potent and selective S1P1 receptor modulator. BMS-986104 is effective in a mouse EAE model, which is comparable to FTY720. Mechanistically, BMS-986104 exhibites excellent remyelinating effects on lysophosphatidylcholine (LPC)-induced demyelination in a three-dimensional brain cell culture assay.

LX2932 is an orally active LX2931 (HY-14370) analogue and S1P/S1PR signaling axis modulator. LX2932 yields a dose-dependent decrease in circulating lymphocyte numbers. LX2932 improves collagen-induced arthritis.

CS-0777 is a selective, orally active sphingosine 1-phosphate receptor-1 modulator. CS-0777 can be used in the research of autoimmune diseases.

Fingolimod (hydrochloride) (Standard) is the analytical standard of Fingolimod (hydrochloride). This product is intended for research and analytical applications. Fingolimod hydrochloride (FTY720), an analog of sphingosine, is a potent sphingosine 1-phosphate (S1P) receptors modulator. Fingolimod hydrochloride is phosphorylated by sphingosine kinases, particularly by SK2, and then binds S1PR1, 3, 4, and 5. Fingolimod hydrochloride induces the internalization of S1P1, and consequently, inhibits S1P activity. Fingolimod hydrochloride also is a pak1 activator.

VPC 23019 (Standard) is the analytical standard of VPC 23019 (HY-108490). This product is intended for research and analytical applications. VPC 23019, an aryl amide-containing Sphingosine 1-phosphate (S1P) analog, is a competitive antagonist at the S1P1 and S1P3 receptors (pK_i= 7.86 and 5.93, respectively) and an agonist at the S1P4 and S1P5 receptors (pEC₅₀= 6.58 and 7.07, respectively).

S1PR-MO-1 is the modulator of sphingosine-1-phosphate receptor, used for research of hyperproliferative, inflammatory diseases.