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Purity: ≥98%
PRT062607 (also known as P505-15, BIIB-057) HCl is a novel, potent, highly selective and orally bioavailable small molecule Syk inhibitor with potential anti-inflammatory activity. It inhibits Syk with an IC50 of 1 nM in cell-free assays, and shows >80-fold selectivity for Syk over other kinases such as Fgr, Lyn, FAK, Pyk2 and Zap70. PRT062607 produced excellent in vivo anti-inflammatory activity in two rodent models of rheumatoid arthritis. P505-15 successfully inhibited SYK-mediated B-cell receptor signaling and decreased cell viability in NHL and CLL. PRT062607effectively 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.
| ln Vitro |
PRT062607 (P505-15) is a brand-new, extremely effective, and strong small-molecule inhibitor of Syk that is taken orally. Two distinct pure kinase assays are used to investigate PRT062607's efficacy against its target kinase Syk. Half-maximum Syk inhibition needed 6±0.2 nM (mean±SEM) according to a FRET test. A radioactive enzyme assay yields a Syk IC50 of 2.1±0.4 nM (mean±SEM), indicating similar potency. PRT062607 effectively suppresses Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM) and B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) in human whole blood[1].
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| ln Vivo |
When PRT062607 (P505-15) is administered orally to mice in the CAIA model, the average reduction in paw inflammation, as determined by daily scoring of inflammation in comparison to vehicle controls, is 12, 44, and 87%. At the conclusion of the study, the average plasma concentration (C average over 24 hours) was determined to be 0.38, 0.95, and 1.47 μM. Mice given 30 mg/kg of PRT062607 showed a considerable reduction in joint degeneration, to the point that the mice could not be distinguished from normal mice. By the end of the research, the majority of the animals (seven out of eight) in the rat CIA model (mean inflammation score±SEM=0.63±1.1; p<0.0001 versus vehicle) had totally suppressed inflammation due to the high dose of PRT062607 (15 mg/kg bid)[1].
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| References |
[1]. Coffey G, et al. Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J Pharmacol Exp Ther. 2012 Feb;340(2):350-9
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| Molecular Formula |
C19H23N9O.HCL
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| Molecular Weight |
429.91
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| CAS # |
1370261-97-4
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| Related CAS # |
PRT062607;1370261-96-3
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| SMILES |
O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)N.[H]Cl
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| Chemical Name |
4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2S)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride
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| Synonyms |
P505-15; P-50515; PRT2607; PRT062607; P50515; BIIB057; PRT-062607; PRT 062607; PRT-2607; PRT 2607; P-505-15; P 505-15; P 50515; BIIB-057; BIIB 057.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline:30mg/mL Solubility in Formulation 5: 50 mg/mL (116.30 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3261 mL | 11.6303 mL | 23.2607 mL | |
| 5 mM | 0.4652 mL | 2.3261 mL | 4.6521 mL | |
| 10 mM | 0.2326 mL | 1.1630 mL | 2.3261 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01652937 | Withdrawn | Drug: BIIB057 Drug: Placebo |
Rheumatoid Arthritis | Biogen | August 2012 | Phase 2 |
P505-15 selectively inhibits proliferation of Syk-dependent B cell lines.J Pharmacol Exp Ther.2012 Feb;340(2):350-9. |
P505-15 attenuates antibody-induced inflammation in a mouse model of rheumatoid arthritis.J Pharmacol Exp Ther.2012 Feb;340(2):350-9. |
Oral administration of P505-15 significantly ameliorates the severity and development of arthritis in the rat CIA model.J Pharmacol Exp Ther.2012 Feb;340(2):350-9. |
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