PRT062607 (P505-15) HCl

製品コードS8032 バッチS803203

印刷

化学情報

Chemical Structure Synonyms BIIB057, PRT-2607 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H23N9O.HCl
分子量 429.91 CAS No. 1370261-97-4
Solubility (25°C)* 体外 DMSO 86 mg/mL (200.04 mM)
Water 30 mg/mL (69.78 mM)
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
Saline
30.0mg/ml Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 PRT062607 (P505-15, BIIB057, PRT-2607) is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays, >80-fold selective for Syk than Fgr, PAK5, Lyn, FAK, Pyk2, FLT3, MLK1 and Zap70.
in vitro PRT062607(P505-15) anti-SYK activity is at least 80-fold greater than its affinity for other kinases. at least 80-fold greater than its affinity for other kinases. PRT062607 potently inhibits 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] PRT062607 inhibits 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. PRT062607 furthermore inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering. [2]
in vivo The pharmacokinetic/pharmacodynamic relationship predicted that 70% Syk suppression is maintained in mice over a 24h period after 30 mg/kg dosing. At 15 mg/kg, Syk inhibition ranges from 7.5% (Cmin) to 78.4% (Cmax) with an average inhibition of 67% over 24 h. Oral administration of PRT062607 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy is observed at concentrations that specifically suppressed Syk activity by 67%.[1]

プロトコル(参考用のみ)

キナーゼアッセイ fluorescence resonance energy transfer (FRET) assay
The extent of substrate phosphorylation by Syk is measured in the presence of various PRT062607 concentrations. Syk activity is determined by a fluorescent antibody specific for phosphorylated tyrosine by using the increase of FRET. Twelve concentrations are tested for dose response. Specificity and potency of kinase inhibition is determined by evaluation of PRT062607 in the Millipore KinaseProfiler panel of 270 independent purified kinase assays. For profiling, PRT062607 is tested in duplicate at two concentrations at a fixed concentration of ATP. Subsequently, IC50 determinations using the radioactive assays are carried out at an ATP concentration optimized for each individual kinase. All radioactive ATP incorporationenzyme assays are performed at Millipore.
細胞アッセイ 細胞株 Syk-dependent BaF3 cell
濃度 ~6 μM
反応時間 3 days
実験の流れ

CellTiter Glo
動物実験 動物モデル Mouse Collagen Antibody-Induced Arthritis Model
投薬量 5, 15, 30 mg/kg, b.i.d.
投与方法 Oral

カスタマーフィードバック

Data from [Data independently produced by Exp Dermatol, 2014, 23(12), 884-9]

Data from [Data independently produced by , , Nature, 2015, 521(7552): 357-61]

Data from [Data independently produced by , , Nature, 2015, 521(7552): 357-61]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Identification and structural characterization of small molecule inhibitors of PINK1 [ Sci Rep, 2024, 14(1):7739] PubMed: 38565869
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] PubMed: 37462944
Neuronal C-Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain [ Adv Sci (Weinh), 2023, 10(10):e2205397] PubMed: 36727833
Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography [ J Thromb Haemost, 2023, 21(8):2236-2247] PubMed: 37068592
YES1 Kinase Mediates the Membrane Removal of Rescued F508del-CFTR in Airway Cells by Promoting MAPK Pathway Activation via SHC1 [ Biomolecules, 2023, 13(6)949] PubMed: 37371529
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226] PubMed: 36266272
Drug-microenvironment perturbations reveal resistance mechanisms and prognostic subgroups in CLL [ Mol Syst Biol, 2022, 18(8):e10855] PubMed: 35959629
Listeria toxin promotes phosphorylation of the inflammasome adaptor ASC through Lyn and Syk to exacerbate pathogen expansion [ Cell Rep, 2022, 38(8):110414] PubMed: 35196496

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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