Table 1.
S1P modulators in experimental models of kidney disease
| Compound Name | Agonist/Antagonist | Target Specificity | Model | Phenotype (A, NE, E) | Reference |
|---|---|---|---|---|---|
| ABC294640 | Antagonist | SPHK2 | LN | Aa | 250 |
| Berberine | Antagonist | SPHK1/S1PR2 | DN | A | 251 |
| CAY10444 | Antagonist | S1PR3 | IRI | NE | 165 |
| CAY10621 | Antagonist | SPHK1 | IRI | E | 164 |
| FTY720 | Agonist | S1PR1/3/4/5 | AngII-induced hypertension in rats | A | 162 |
| FTY720 | Agonist | S1PR1/3/4/5 | STZ-induced DN | A | 148 |
| FTY720 | Agonist | S1PR1/3/4/5 | GN | A | 252, 253 |
| FTY720 | Agonist | S1PR1/3/4/5 | IRI | A | 142 |
| FTY720 | Agonist | S1PR1/3/4/5 | IRI in Sphk2 knockout mice | NE | 254 |
| FTY720 | Agonist | S1PR1/3/4/5 | Cisplatin-induced AKI in S1PR1 knockout mice | NE | 255 |
| FTY720 | Agonist | S1PR1/3/4/5 | PKD | A | 256 |
| FTY720 | Agonist | S1PR1/3/4/5 | AAV | A | 257 |
| FTY720 | Agonist | S1PR1/3/4/5 | IRI | A | 147 |
| FTY720 | Agonist | S1PR1/3/4/5 | Kidney allograft survival (canine) | A | 211 |
| FTY720 | Agonist | S1PR1/3/4/5 | Kidney allograft survival | A | 213 |
| FTY720 | Agonist | S1PR1/3/4/5 | Kidney allograft survival | A | 212 |
| FTY720 | Agonist | S1PR1/3/4/5 | Kidney allograft survival | NE | 214 |
| Isoflurane | Agonist | SPHK1 | IRI | A | 163 |
| JTE-013 | Antagonist | S1PR2 | IgAN | A | 194 |
| JTE-013 | Antagonist | S1PR2 | IRI | A | 165 |
| KRP-203 | Agonist | S1PR1/4 | LN | A | 258 |
| MT-1303 | Antagonist | S1PR1 | LN | A | 259 |
| RP-101075 | Agonist | S1PR1/5 | LN | A | 203 |
| RPC1063 (Ozanimod) | Agonist | S1PR1/5 | LN | A | 203 |
| S1P | Agonist | S1PR1? | Hepatic IRI | A | 260 |
| S1P | Agonist | S1PR1? | IRI in Sphk2 knockout mice | A | 254 |
| S1P | Agonist | S1PR1 | RI nephropathy | A | 182 |
| SEW2871 | Agonist | S1PR1 | STZ-induced DN | A | 148 |
| SEW2871 | Agonist | S1PR1 | IRI | A | 142, 177 |
| SEW2871 | Agonist | S1PR1 | IRI | A | 164 |
| SEW2871 | Agonist | S1PR1 | AAV | NE | 257 |
| SEW2871 | Agonist | S1PR1 | IRI | A | 147 |
| SID46371153 | Agonist | S1PR2 | IRI | E | 165 |
| SK-II | Antagonist | SPHK1/SPHK2 | IRI | E | 164 |
| TY52156 | Antagonist | S1PR3 | AAV | NE | 257 |
| VPC-23019 | Antagonist | S1PR1/3 | IgAN | NE | 194 |
| VPC-23019 | Antagonist | S1PR1/3 | LPS-induced renal injury | A | 261 |
| VPC-23019 | Antagonist | S1PR1/3 | Hepatic IRI | Eb | 260 |
| VPC-44116 | Antagonist | S1PR1 | IRI | Ec | 142 |
| VPC-44116 | Antagonist | S1PR1 | IRI | Ec | 147 |
| W146 | Antagonist | S1PR1 | IRI | NE | 165 |
GN indicates anti–Thy1.1.-induced GN. SPHK, sphingosine kinase; A, attenuation; S1PR, sphingosine-1-phosphate receptor; DN, diabetic nephropathy; NE, no effect; E, exacerbation; PKD, polycystic kidney disease; RI nephropathy, radiation-induced nephropathy.
a
Improved glomerular pathology but not improved proteinuria.
b
Reverses S1P-mediated protective effect.
c
Reverses FTY720-mediated protective effect.