CAS NO: | 1370261-96-3 |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
Cas No. | 1370261-96-3 |
别名 | 2-[[(1R,2S)-2-氨基环己基]氨基]-4-[[3-(2H-1,2,3-三唑-2-基)苯基]氨基]-5-嘧啶甲酰胺,P505-15; PRT-2607; BIIB-057 |
Canonical SMILES | NC(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)=O |
分子式 | C19H23N9O |
分子量 | 393.45 |
溶解度 | DMF: 50 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 25 mg/ml,Ethanol: 10 mg/ml |
储存条件 | Store at -20°C |
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
产品描述 | PRT062607(P505-15; PRT-2607; BIIB-057) is a highly specific and potent inhibitor of Syk with IC50 of 1-2 nM; >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70.IC50 value: 1-2 nM [1]Target:Syk kinase inhibitorin vitro: In human whole blood, 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) [1]. P505-15 successfully inhibited SYK-mediated B-cell receptor signaling and decreased cell viability in NHL and CLL [2]. PRT318 and P505-15 effectively antagonize CLL cell survival after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering [3].in vivo: Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). Oral administration of P505-15 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis [1]. Oral dosing in mice prevented BCR-mediated splenomegaly and significantly inhibited NHL tumor growth in a xenograft model. In addition, combination treatment of primary CLL cells with P505-15 plus fludarabine produced synergistic enhancement of activity at nanomolar concentrations [2]. [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. [2]. Spurgeon SE, 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 Feb;344(2):378-87. [3]. Hoellenriegel J, et al. Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration. Leukemia. 2012 Jul;26(7):1576-83. |