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PRN1008
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PRN1008图片
CAS NO:1575596-29-0
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
PRN1008 (PRN1008) 是 Bruton's Tyrosine Kinase (BTK) 的可逆共价、选择性和口服活性抑制剂,IC50 为 1.3 nM。
Cas No.1575596-29-0
别名PRN1008
Canonical SMILESNC1=C2C(C3=C(C=C(OC4=CC=CC=C4)C=C3)F)=NN([C@H]5CN(CCC5)C(/C(C#N)=C/C(C)(N6CCN(C7COC7)CC6)C)=O)C2=NC=N1
分子式C36H40FN9O3
分子量665.76
溶解度DMSO : ≥ 130 mg/mL (195.27 mM)
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

PRN1008 is a reversible covalent, selective and oral active inhibitor of Bruton's Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.

PRN1008 is a reversible covalent inhibitor of Bruton's Tyrosine Kinase (BTK), with an IC50 of 1.3±0.5 nM. PRN1008 is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by PRN1008 results in a slow off-rate demonstrated by retention of 79±2% of binding to BTK in PBMC 18 hours after washing away the compound in vitro. The covalent cysteine binding is completely reversible after denaturation of the target. Anti-IgM induces human B cell proliferation (10% serum) and B cell CD69 expression are inhibited by PRN1008 with IC50 of 5±2.4 nM and 123±38 nM, respectively[2].

In vivo PRN1008 demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. PRN1008 also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification[2].

[1]. Smith PF, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376. [2]. Hill RJ, Bradshaw JM, Bisconte A, Tam D, Owens TD, Brameld KA, Smith PF, Funk JO, Goldstein DM, Nunn PA. Preclinical Characterization of PRN1008, a Novel Reversible Covalent Inhibitor of BTK that Shows Efficacy in a RAT Model of Collagen-Induced Arthritis. Annals of the Rheumatic Diseases 2015; 74(Suppl 2): 216.