Ezatiostat inhibits the enzyme, glutathione S-transferase P1-1, GSTP1-1 is a key regulatory protein that can signal the cell to either make more blood elements or if the cell is cancerous to die.This inhibition induces a dissociation of GST P1-1 from its complex with c-jun N-terminal kinase (JNK)/c-Jun and activates signaling pathways that lead to cell proliferation and differentiation of normal hematopoietic cells and apoptosis of malignant cells.It has shown significant clinical activityof ezatiostat, a glutathione S-transferase P1-1 inhibitor in clinical development for the treatment of low- to intermediate-risk MDS.
| Molecular Weight | 529.65 |
| Formula | C27H35N3O6S |
| CAS Number | 168682-53-9 |
| Solubility (25°C) | DMSO 80 mg/mL Ethanol 80 mg/mL |
| Storage | -20°C, dry, sealed |
| 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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