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Rilzabrutinib(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。
Rilzabrutinib(PRN1008)图片
CAS NO:1575596-29-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 665.77
Formula C36H40FN9O3
CAS No. 1575596-77-8
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM
Water: N/A
Ethanol: N/A
Chemical Name(S,E)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-methyl-4-(4-(oxetan-3-yl)piperazin-1-yl)pent-2-enenitrile
SynonymsPRN-1008; PRN1008; PRN 1008
实验参考方法
In Vitro

In vitro activity: PRN1008 is a highly potent, reversible covalent inhibitor of BTK (Bruton’s Tyrosine Kinase) with an IC50 of 1.3 nM. PRN1008 was found to be very potent against BTK and highly selective when tested against 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. PRN1008 was safe and well-tolerated following oral administration, and achieved high, sustained levels of BTK occupancy in peripheral blood mononuclear cells. PRN1008 is currently under Phase I development as a therapeutic agent for rheumatoid arthritis.


Kinase Assay: PRN1008 is very potent against BTK (IC50=1.3±0.5 nM) and highly selective against 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


Cell Assay: Anti-IgM induced human B cell proliferation (10% serum) and B cell CD69 expression (whole blood) were inhibited by PRN1008 with IC50 of 5 ± 2.4 nM and 123 ± 38 nM, respectively. PRN1008 did not block EGFR signaling in epithelial cells or TCR and calcium flux stimulated T cell activation. PRN1008 also did not block IL-4 stimulation of B cells and did not exhibit cytotoxicity in an epithelial cell line HCT-116. In addition, PRN1008 did not block antibody dependent cell-mediated cytotoxicity in combination with anti-CD20
antibodies allowing for potential combination therapies. In vivo PRN1008 demonstrated enduring pharmacodynamic effects after the compound had cleared from circulation, consistent with extended target residence time. PRN1008 also reversed and completely suppressed collagen-induced arthritis in rats in a dose dependent manner which allowed correlation of target occupancy and disease modification.

In VivoIn 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[
Animal model Rats with collagen-induced arthritis (CIA) model
Formulation & Dosage 10, 20, 40 mg/kg
References Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376; Annals of the Rheumatic Diseases 2015; 74(Suppl 2): 216.