Table 3.
PSα scores and ranks for phospholipidosis-relevant targets
| Mechanism | Target | Rank | PSα |
|---|---|---|---|
| 1 | Sphingomyelin phosphodiesterase (SMPD) (h) | 225 | 55 |
| Lysosomal Phospholipase A1 (LYPLA1) (r) | 163 = | 90 | |
| Phospholipase A2 (PLA2) (h) | 152 = | 97 | |
| 3 | Elongation of very long chain fatty acids protein 6 (ELOVL6) (h) | 1203 = | -10 |
| Acyl-CoA desaturase (SCD) (m) | 610 = | 0 | |
| 4 | 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) (h) | 456 = | 10 |
| Squalene monooxygenase (SQLE) (h) | 437 = | 14 | |
| Lanosterol synthase (LSS) (h) | 114 = | 134 | |
Table of the targets suggested by Sawada et al. [11] which are included in our model and their ranks based on the PSα score; tied ranks are denoted by =. The targets are grouped into their different mechanisms: 1) Inhibition of phospholipase activity; 2) Inhibition of lysosomal enzyme transport (not represented in this table); 3) Enhanced phospholipid biosynthesis; 4) Enhanced cholesterol biosynthesis. While Sawada et al. worked with human hepatoma HepG2 cells, [11] we also consider the corresponding genes in other species. Where homologous ChEMBL targets from two species were part of our model, for instance both human and rat versions of lanosterol synthase appeared, the higher scoring one is listed in this table; all its entries are from human (h), rat (r) or mouse (m).