PRT062607 Hydrochloride
PRT062607 Hydrochloride is a highly selective and novel SYK inhibitor with IC50 value of 1 nM. Spleen tyrosine kinase (SYK) is a cytoplasmic tyrosine kinase and primarily expressed in hematopoietic cells including B-cells.
PRT062607 Hydrochloride is an orally bioavailable SYK inhibitor and its affinity for SYK is at least 80-fold greater than other kinases. In NHL cell lines, PRT062607 Hydrochloride inhibits SYK activation and induces caspase dependent apoptosis. Also, PRT062607 Hydrochloride inhibited SYK and caused apoptosis of the tumor B-cell line [1].
PRT062607 Hydrochloride effectively antagonize CLL cell survival after BCR triggering. Moreover, they inhibit the secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell transfer toward beneath stromal cells, the tissue homing chemokines CXCL13 and CXCL12 [2].
In a mouse xenograft model, mice dosed with all three concentrations (twice daily with 10, 15, or 20 mg/kg) of PRT062607 Hydrochloride were protected from Ramos tumor growth [1].
References:
[1]. Spurgeon SE, Coffey G, Fletcher LB, et al. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia. J Pharmacol Exp Ther, 2013, 344(2): 378-387.
[2]. Hoellenriegel J, Coffey GP, Sinha U, et al. Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration. Leukemia, 2012, 26(7): 1576-1583.
- 1. Panagi I, Jennings E, et al. "Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization." Cell Host Microbe. 2020;27(1):41–53.e6. PMID:31862381
- 2. Tümmler C, Dumitriu G, et al. "SYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells in Vitro." Cancers (Basel). 2019 Feb 10;11(2). pii: E202. PMID:30744170
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 429.91 |
| Cas No. | 1370261-97-4 |
| Formula | C19H24ClN9O |
| Synonyms | PRT 062607 hydrochloride;PRT-062607 hydrochloride |
| Solubility | ≥21.5 mg/mL in DMSO; insoluble in EtOH; ≥83.2 mg/mL in H2O with gentle warming |
| Chemical Name | 4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2R)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride |
| SDF | Download SDF |
| Canonical SMILES | NC(C1=C(NC2=CC(N3N=CC=N3)=CC=C2)N=C(N[C@H]4[C@H](N)CCCC4)N=C1)=O.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
Primary B-cells, SU-DHL6 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 24 hours |
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Applications |
To compare the relative sensitivity of primary versus tumor B-cells, the mixing experiments in which SU-DHL6 was combined with human whole blood and treated with P505-15 were performed. Under these conditions, whereas the tumor B-cell line underwent apoptosis in response to SYK inhibition, primary B-cells did not. |
| Animal experiment: [1] | |
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Animal models |
NOD/SCID mice injected with Ramos cells |
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Dosage form |
Oral administration, 10, 15, or 20 mg/kg, twice daily |
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Applications |
A statistically significant reduction in average tumor weight was achieved in all dosing groups relative to vehicle control. It revealed that submicromolar concentrations of P505-15 prevented tumor formation by an aggressive NHL cell line in mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Spurgeon S E, Coffey G, Fletcher L B, et al. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia. Journal of Pharmacology and Experimental Therapeutics, 2013, 344(2): 378-387. |
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| Description | PRT062607 (P505-15) HCl is a novel, highly selective inhibitor of Syk with IC50 of 1 nM, >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70. | |||||
| Targets | Syk | Fgr | MLK1 | |||
| IC50 | 1 nM | 81 nM | 88 nM | |||
Quality Control & MSDS
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Chemical structure
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