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Purity: ≥98%
PRT-060318 3HCl (also known as PRT318 3HCl) is a novel, potent, selective inhibitor of the Syk tyrosine kinase, as an approach to HIT treatment. It was discovered that PRT-060318 is a strong inhibitor of pure Syk kinase. When PRT-060318 was assessed at a concentration of 50 nM in a wide range of kinase enzyme tests, Syk kinase was inhibited by 92%, while the activities of all other kinases retained more than 70% of their activity. Furthermore, PRT-060318 could inhibit the aggregation of human platelets induced by convulxin in a dose-responsive manner. Furthermore, it was discovered that PRT-060318 could inhibit the rises in intracellular calcium in platelets treated with convulxin in a dose-responsive manner.
| ln Vitro |
PRT318 inhibits platelet activation through the ITAM receptor complex GPVI/FcRγ, but not through G-protein coupled receptors such as ADP or thrombin[1]. PRT318 successfully inhibits the survival of CLL (chronic lymphocytic leukemia) cells in nurse-like cell co-cultures and following BCR triggering. After BCR triggering, PRT318 inhibits the phosphorylation of Syk and extracellular signal-regulated kinase[2].
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| ln Vivo |
PRT060318 is administered intravenously to target maximal inhibition of Syk kinase activity and significantly prevent arterial thrombosis in both rabbit and pig models. Because PRT060318 completely inhibits platelet aggregation induced by CVXN, it has no effect on platelet aggregation induced by ADP, and it does not prolong the duration of bleeding in the ears, it exhibits remarkable antithrombotic activity in pigs[3]. Moreover, PRT318—a Syk inhibitor—is an active component of HIT. The thrombocytopenic and thrombotic effects of HIT IC in vivo are limited by inhibiting Syk signaling with the orally bioavailable PRT318[1].
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| Enzyme Assay |
PRT-060318 (also known as PRT318) is a novel, potent, selective Syk tyrosine kinase inhibitor used to treat HIT. It was discovered that PRT-060318 is a strong inhibitor of pure Syk kinase. When PRT-060318 was assessed at a concentration of 50 nM in a wide range of kinase enzyme tests, Syk kinase was inhibited by 92%, while the activities of all other kinases retained more than 70% of their activity.
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| Cell Assay |
The number of cells treated with different PRT318 doses is monitored over time. The growth of the sensitive cell lines is dose-dependently inhibited by PRT318. The recommended doses of PRT318 are applied to two sensitive (LY7 and LY18) and two resistant (LY3 and LY4) cell lines.
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| Animal Protocol |
Mice: On day 0, KKO (20 mg/kg body weight, intraperitoneally) is administered to mice in the Heparin-induced thrombocytopenia (HIT) model. A sex- and weight-matched experimental group and a control group are created from the mice. Days 1 through 7 see the oral gavage of PRT318 (30 mg/kg body weight) to six experimental mice (n = 6), while days 8 through 14 see the oral administration of vehicle alone (sterile water) to six control mice (n = 6). Subcutaneous heparin (1600 U/kg body weight) is administered once daily to both groups. To make injections and blood collections easier on the mice, isoflurane is inhaled.
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| References |
| Molecular Formula |
C18H26CL2N6O
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| Molecular Weight |
413.3446
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| CAS # |
1194961-19-7
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| Related CAS # |
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| SMILES |
Cl[H].Cl[H].O=C(C1=C([H])N=C(N=C1N([H])C1=C([H])C([H])=C([H])C(C([H])([H])[H])=C1[H])N([H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[C@]1([H])N([H])[H])N([H])[H]
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (73.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4193 mL | 12.0966 mL | 24.1932 mL | |
| 5 mM | 0.4839 mL | 2.4193 mL | 4.8386 mL | |
| 10 mM | 0.2419 mL | 1.2097 mL | 2.4193 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Platelet function studies. (A) Aggregation of human PRP was done to compare the effect of PRT318 on convulxin versus ADP.Blood.2011 Feb 17;117(7):2241-6. |
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HIT IC-mediated platelet aggregation in vitro. (A) Human PRP (250 000 platelets/μL) was incubated at 37°C for 15 minutes with aliquots of a mixture of PF4 and heparin (1.5:1 molar ratio) containing 5 μg PF4.Blood.2011 Feb 17;117(7):2241-6. |
HIT IC-mediated thrombocytopenia in vivo.Blood.2011 Feb 17;117(7):2241-6. |
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