YU142670 is a selective inhibitor against OCRL1/INPP5F (IC50 = 0.71 μM; substrate = PI(4,5)P2) and OCRL2/INPP5B (IC50 = 0.53 and 1.78 μM; substrate = PI3 and INPP5B/PI(4,5)P2, respectively) by targeting OCRL catalytic domain without affecting INPP5A, INPP5E, PTEN, SHP1, shrimp alkaline phosphatase, sphingomyelinase, or SYNJ1. YU142670 causes an increased PI(4,5)P2/PI4P ratio in human skin fibroblasts (by 50%; 50 μM for 1 h) and induces upregulated actin nucleation and ruffle activity at the plasma membrane without obvious cytotoxicity. Consistent with the negative regulatory role of PtdIns(4,5)P2 against the calcium channel mucolipin-1 (MCOLN1) that controls autophagosome-lysosome fusion, ehnahced autophagosome accumulation is observed in human kidney proximal tubule cells (PTCs) upon YU142670 (25 μM for 3 hr) or OCRL shRNA treatment.
| Molecular Weight | 203.22 |
| Formula | C8H5N5S |
| CAS Number | 133847-06-0 |
| Solubility (25°C) | DMSO: 2 mg/mL (warmed) |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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