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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
CNX-774 (CNX774) is an irreversible/covalent, orally bioavailable, and highly selective inhibitor of BTK (Bruton's tyrosine kinase) with potential anticancer activity. It inhibits BTK with an IC50 of<1 nM. CNX-774 acts by forming a covalent bond with the Cys-481 residue within the active site of BTK, which is an key enzyme in the B-cell antigen receptor (BCR) signaling pathway, and also plays an pivotal role in the maturation of mast cells activation and B cells.
ln Vitro |
In Ramos cells, CNX-774 significantly reduces Btk activity with an IC50 of 1–10 nM. Strong time- and dose-dependent Btk occupancy in Ramos cells is shown by CNX-774[1].
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ln Vivo |
CNX-774 does not form covalent bonds with any of the mid-level abundance human plasma proteins and is stable and non-reactive in fresh human and rat whole blood[1]. In a range of tests intended to evaluate off-target reactivity towards abundant cellular thiols and blood proteins, CNX-774 exhibits strong inhibitory activity towards the intended target, Btk, while achieving exceptional specificity[1].
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Animal Protocol |
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References |
[1]. Matthew Labenski, et al. In Vitro Reactivity Assessment of Covalent Drugs Targeting Bruton's Tyrosine Kinase.
[2]. Akintunde Akinleye, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. |
Molecular Formula |
C26H22FN7O3
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Molecular Weight |
499.5
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CAS # |
1202759-32-7
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Related CAS # |
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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
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InChi Key |
VVLHQJDAUIPZFH-UHFFFAOYSA-N
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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)
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Chemical Name |
4-(4-((4-((3-acrylamidophenyl)amino)-5-fluoropyrimidin-2-yl)amino)phenoxy)-N-methylpicolinamide
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Synonyms |
CNX 774; CNX-774; CNX774;
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0020 mL | 10.0100 mL | 20.0200 mL | |
5 mM | 0.4004 mL | 2.0020 mL | 4.0040 mL | |
10 mM | 0.2002 mL | 1.0010 mL | 2.0020 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
BTK structure. BTK belongs to the Tec family of protein tyrosine kinases and is composed of the PH (pleckstrin homology), TH (Tec homology), SH3 (Src homology 3) SH2 (Src homology 2), and SH 1/TK (Src homology1/Tyrosine kinase) domains.J Hematol Oncol. 2013 Aug 19;6:59. td> |
BTK signaling pathway. BTK translocates to the plasma membrane by interacting with PIP3 to become membrane-bound where it undergoes sequential activation through trans-phosphorylation by Lyn and Syk kinases, followed by autophosphorylation. J Hematol Oncol. 2013 Aug 19;6:59. td> |