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CNX-774
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。
CNX-774图片
CAS NO:1202759-32-7
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
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)499.5
FormulaC26H22FN7O3
CAS No.1202759-32-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (4.0 mM)
SMILESO=C(NC)C1=NC=CC(OC2=CC=C(NC3=NC=C(F)C(NC4=CC=CC(NC(C=C)=O)=C4)=N3)C=C2)=C1
SynonymsCNX 774; CNX-774; CNX774;

Chemical Name: 4-(4-((4-((3-acrylamidophenyl)amino)-5-fluoropyrimidin-2-yl)amino)phenoxy)-N-methylpicolinamide

InChi Key: VVLHQJDAUIPZFH-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H22FN7O3/c1-3-23(35)31-17-5-4-6-18(13-17)32-24-21(27)15-30-26(34-24)33-16-7-9-19(10-8-16)37-20-11-12-29-22(14-20)25(36)28-2/h3-15H,1H2,2H3,(H,28,36)(H,31,35)(H2,30,32,33,34)

实验参考方法
In Vitro

In vitro activity: CNX-774 is a potent, irreversible/covalent, orally bioactive, and highly selective BTK (Bruton’s tyrosine kinase) inhibitor with IC50 of<1 nM. It forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme.


Kinase Assay: In biochemical assays, CNX-774 has demonstrated potent inhibition of Btk with an IC50 of<1nM in a continuous-read assay. The covalent bonding of CNX-774 to Btk was confirmed by incubating recombinant Btk protein with a 10-fold molar excess of CNX-774 for 1 hour at room temperature and analysis by MALDI-TOF MS. A shift of protein mass corresponding to the molecular weight of CNX-774 confirmed the covalent bonding of CNX-774 to Btk. Digestion of the covalently bonded Btk with pepsin followed by MSMS analysis established the bonding of CNX-774 to Cys-481.


Cell Assay: In cellular assays, CNX-774 demonstrates potent inhibitory activity towards BTK with IC50 of 1-10 nM by targeting Cys-481 residue within the ATP binding site of the enzyme. Cellular potency as well as prolonged duration of action of CNX-774 was demonstrated in Ramos cells by using a biotinylated covalent probe that targets the same Cysteine residue as CNX-774. CNX-774 was found to be>90% extractable after 2 hrs of incubation in both rat and human whole blood. These results demonstrate that CNX-774 has potent inhibitory activity towards the intended target, Btk, while achieving remarkable specificity in a variety of assays designed to assess off-target reactivity towards abundant cellular thiols and blood proteins.

In Vivo
Animal model
Formulation & Dosage
References J Hematol Oncol. 2013 Aug 19;6:59.