TAPI blocks the spontaneous and PMA-induced release of TNF-alpha from transfected cells. TAPI-1, an inhibitor of ADAMs, reduced constitutive and muscarinic receptor-stimulated sAPP alpha release in HEK-293 cells stably expressing M3 muscarinic receptors. TAPI-1 with the EGFR inhibitor AG1478 exhibits deactivated AREG/EGFR/ERK signaling pathway and reduces pro-inflammatory cytokines release in pSS salivary gland-derived epithelial cells.
| Cell Experiment | |
|---|---|
| Cell lines | LI90 cells |
| Preparation method | Seeding five thousand cells into each well of 96-well plates and assessing their viability by CellTiter-Glo Luminescent Cell Viability assay. Upon serum deprivation for 24 h, tresting the cells with Ang II for 60 h with and without pretreatment with each inhibitor and antagonist. Then addint The assay substrates to each well on the plate and using a luminometer to evaluate the samples |
| Concentrations | 20 μM |
| Incubation time | 60 hours |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 499.60 |
| Formula | C26H37N5O5 |
| CAS Number | 171235-71-5 |
| Solubility (25°C) | DMSO ≥ 50 mg/mL |
| 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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