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AVL-292
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。
AVL-292图片
CAS NO:1202757-89-8
规格:98%
分子量:423.44
包装与价格:
包装价格(元)
10mg电议
50mg电议

产品介绍
Btk inhibitor
CAS:1202757-89-8
分子式:C22H22FN5O3
分子量:423.44
纯度:98%
存储:Store at -20°C

Background:

CC-292, formerly known as AVL-292, is an orally active, potent irreversible small molecule inhibitor of BTK with IC50 of 0.5 nM and EC50 of 8 nM. [1]
The B cell receptor (BCR) signaling pathway plays an important role in the fate and function of B cells by modulating cellular selection, maturation, proliferation, and production of antibody.
BTK, which is a tyrosine kinase member of the Tec kinase family, is a unique therapeutic target among kinases in the pathway BCR signaling. Studies showed that loss of gene function mutations of BTK in humans consequently leads to X-linked agammaglobulinaemia (XLA), characterized by a complete lack of B cells, low concentrations of serum Ig, and recurring infections, which implies that BTK is required in the development and immunoglobulin production of B cells. CC-292 inhibits BTK by the formation of a covalent bond with Cys481 residue. [2]
The inhibitory activity of CC-292 has been examined in immunoblot analysis, which showed that CC-292 potently inhibits auto-phosphorylation in human naive primary B cells. Furthermore, CD69 upregulation tested by ?ow cytometry tracking also exhibited a dose-dependent reduction in CD69 expression with increasing levels of CC-292 in vitro. Covalent probe analysis of human B cells coupled with enzyme linked immunosorbent assay (ELISA) quanti?cation methods illustrated 42% BTK occupancy in a 1h incubation with CC-292 of 10 nM. [1, 2]
Studies in vivo for CC-292 has been conducted. CIA model in mice was orally treated with CC-292, which demonstrated a positive correlation between BTK occupancy and inhibition of the disease. In addition, CC-292 was assessed with clinical trials, which showed a T1/2 of 1.9h and suggested efficacy in B-NHL, WM, and CLL patients. [2]
参考文献:
[1].Evans E K, Aslanian S, Karp R, et al. Inhibition of Btk with CC-292 provides early pharmacodynamic assessment of activity in mice and humans[J]. Journal of Pharmacology and Experimental Therapeutics, 2013, 346(2): 219-228.
[2].Aalipour A, Advani R H. Bruton tyrosine kinase inhibitors: a promising novel targeted treatment for B cell lymphomas[J]. British journal of haematology, 2013, 163(4): 436-443.