CAS NO: | 1575596-29-0 |
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 |
Cas No. | 1575596-29-0 |
别名 | PRN1008 |
Canonical SMILES | NC1=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 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 | 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. |