CAS NO: | 1202759-32-7 |
规格: | ≥98% |
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 |
Molecular Weight (MW) | 499.5 |
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Formula | C26H22FN7O3 |
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) | |
SMILES | O=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 |
Synonyms | CNX 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) |
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. |
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In Vivo | |
Animal model | |
Formulation & Dosage | |
References | J Hematol Oncol. 2013 Aug 19;6:59. |