1202759-32-7
1202759-32-7 structure
- Name: CNX-774
- Chemical Name: 4-{4-[(4-{[3-(Acryloylamino)phenyl]amino}-5-fluoro-2-pyrimidinyl) amino]phenoxy}-N-methyl-2-pyridinecarboxamide
- CAS Number: 1202759-32-7
- Molecular Formula: C26H22FN7O3
- Molecular Weight: 499.496
- Catalog: Biochemical Inhibitor Angiogenesis BTK inhibitor
- Create Date: 2017-01-06 22:21:37
- Modify Date: 2024-01-03 02:34:50
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CNX-774 is a potent, selective, and orally available small molecule inhibitor of Btk (IC50< 1 nM) that forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme.IC50 Value: <1 nM [1]Target: Btk KinaseIn 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. 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.
| Name | 4-{4-[(4-{[3-(Acryloylamino)phenyl]amino}-5-fluoro-2-pyrimidinyl) amino]phenoxy}-N-methyl-2-pyridinecarboxamide |
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| Synonyms |
4-(4-(4-(3-acrylamidophenylamino)-5-fluoropyrimidin-2-ylamino)phenoxy)-N-methylpicolinamide
Coumarin,7-methoxy-3-phenyl-4-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl) 4-{4-[(4-{[3-(Acryloylamino)phenyl]amino}-5-fluoro-2-pyrimidinyl)amino]phenoxy}-N-methyl-2-pyridinecarboxamide 2-Pyridinecarboxamide, 4-[4-[[5-fluoro-4-[[3-[(1-oxo-2-propen-1-yl)amino]phenyl]amino]-2-pyrimidinyl]amino]phenoxy]-N-methyl- 2H-1-Benzopyran-2-one,7-methoxy-3-phenyl-4-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl) 7-Methoxy-3-phenyl-4-(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)coumarin 4-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-7-methoxy-3-phenyl-2H-chromen-2-one CNX-774 |
| Description | CNX-774 is a potent, selective, and orally available small molecule inhibitor of Btk (IC50< 1 nM) that forms a ligand-directed covalent bond with Cys-481, a non-conserved amino acid within the active site of the enzyme.IC50 Value: <1 nM [1]Target: Btk KinaseIn 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. 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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| Related Catalog | |
| References |
[2]. In Vitro Reactivity Assessment of Covalent Drugs Targeting Bruton's Tyrosine Kinase |
| Density | 1.4±0.1 g/cm3 |
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| Molecular Formula | C26H22FN7O3 |
| Molecular Weight | 499.496 |
| Exact Mass | 499.176819 |
| PSA | 136.88000 |
| LogP | 3.15 |
| Index of Refraction | 1.690 |
| Storage condition | -20℃ |
| Hazard Codes | N |
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