P505-15 (also known as PRT062607) is a highly specific and potent, orally bioavailable small molecule spleen tyrosine kinase (Syk) inhibitor (IC50 = 1 nM) with anti-Syk activity that is at least 80-fold greater than its affinity for other kinases. P505-15 potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM) in human whole blood. Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). P505-15 (PRT062607) decreased cell viability in NHL and CLL. Oral administration of P505-15 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. In addition, combination treatment of primary CLL cells with P505-15 plus fludarabine produced synergistic enhancement of activity at nanomolar concentrations.
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Source | J Pharmacol Exp Ther (2013). Figure 1. P505-15 |
| Method | flow cytometry | |
| Cell Lines | Ramos cells | |
| Concentrations | 2 μM | |
| Incubation Time | 72 h | |
| Results | These data are consistent with previous observations that P505-15 is a selective and potent inhibitor of Syk, with no appreciable activity against other BCR-related kinases |
| Molecular Weight | 429.91 |
| Formula | C19H23N9O.HCl |
| CAS Number | 1370261-97-4 |
| Solubility (25°C) | DMSO 80 mg/mL Water 80 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.
| Related Syk Products |
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| Syk-IN-7
Syk-IN-7 is an inhibitor of spleen tyrosine kinase (SYK). |
| Syk-IN-8
Syk-IN-8 is a Syk inhibitor, with antiproliferative activity against multiple hematological tumour cells. |
| ER-27319
ER-27319, an acridone derivative, is a potent and selective SYK inhibitor, and inhibits the tyrosine phosphorylation of SYK and its activity. |
| Dehydroabietinol
Dehydroabietinol is an abietane diterpenoid. Dehydroabietinol has kinase inhibition activity for spleen tyrosine kinase (SYK) with an IC50 value of 46.4 μM. Dehydroabietinol can be used for the research of immune-mediated disease. |
| Cevidoplenib dimesylate
Cevidoplenib is an orally available inhibitor of spleen tyrosine kinase (Syk), with potential anti-inflammatory and immunomodulating activities. |
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