| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
CHMFL-BMX-078 is a highly potent and selective type II irreversible/covalent kinase inhibitor of BMX (bone marrow kinase on chromosome X) kinase with an IC50 of 11 nM. In the DFG-out inactive conformation of BMX, CHMFL-BMX-078 forms a covalent bond with the cysteine 496 residue, exhibiting an IC50 of 11 nM. It achieves at least 40-fold selectivity over BTK kinase (IC50=437 nM) and exhibits a high selectivity profile against the 468 kinases/mutants in the KINOMEscan evaluation. Belonging to the TEC family of nonreceptor tyrosine kinases, BMX plays a crucial role in numerous physiological and pathological processes. Since the exact mechanism of the BMX-mediated signaling pathways is still unknown, CHMFL-BMX-078 would be a helpful pharmacological tool to clarify the specifics of the pathway.
| Targets |
BMX (IC50 = 11 nM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
The substrate polypeptide with 100 μM ATP, 1 μL of serially diluted CHMFL-BMX-078, and BMX or BTK are all present in the kinase reaction system. ATP is added right away to each tube to start the reaction, which is then maintained for an hour at a temperature below 37 °C. 5 μL of solvent reactions are conducted in a 384-well plate after the tube has cooled for five minutes at room temperature. Subsequently, 5 microliters of ADP-Glo reagent is introduced into every well to halt the reaction and use up the residual ATP in 40 minutes. Lastly, a luminescence signal is generated by adding 10 μL of kinase detection reagent into the well and incubating it for 30 minutes. Using an automated plate reader, the luminosity signal is measured[1].
|
|
| Cell Assay |
A nonreceptor tyrosine kinase involved in angiogenesis, proliferation, differentiation, adhesion, and cell motility, bone marrow kinase in the X chromosome (BMX, also known as ETK) is found in these processes. In the DFG-out inactive conformation of BMX, CHMFL-BMX-078 forms a covalent bond with the cysteine 496 residue, exhibiting an IC50 of 11 nM. It achieves at least 40-fold selectivity over BTK kinase (IC50=437 nM) and exhibits a high selectivity profile against the 468 kinases/mutants in the KINOMEscan evaluation. CHMFL-BMX-078 exhibits a binding Kd of 81 nM for BMX kinase in its inactive state and 10200 nM for BMX kinase in its active state. Selectivity over parental BaF3 cells and antiproliferative effects against BaF3-TEL-BMX cells (GI50=0.016 μM) are demonstrated by CHMFL-BMX-078. About 80 times more effective than the C496S mutant (EC50=459 nM) at inhibiting BMX total tyrosine phosphorylation, CHMFL-BMX-078 is against BMX wt (EC50=5.8 nM). In order to clarify the precise mechanism of BMX-mediated signaling pathways, CHMFL-BMX-078 would be a helpful pharmacological tool.
|
|
| Animal Protocol |
Rats: Six male Sprague-Dawley rats, age eight weeks, are given an oral and intravenous drug regimen followed by an overnight fast. The following are the time points for collecting animal blood. The following times are chosen for groups 1, 3, and 5 (intravenous): 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours prior to and following administration. Oral: 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h prior to and following dosage for groups 2, 4, and 6. Plasma is gathered in order to be examined[1].
|
|
| References |
| Molecular Formula |
C33H35N7O6
|
|
|---|---|---|
| Molecular Weight |
625.67
|
|
| Exact Mass |
625.26
|
|
| Elemental Analysis |
C, 63.35; H, 5.64; N, 15.67; O, 15.34
|
|
| CAS # |
1808288-51-8
|
|
| Related CAS # |
|
|
| Appearance |
Solid powder
|
|
| SMILES |
CC1=C(C=C(C=C1)NC2=NC=C(C(=N2)NC)C(=O)NC3=C(C=CC(=C3)NC(=O)C4=CC(=C(C(=C4)OC)OC)OC)C)NC(=O)C=C
|
|
| InChi Key |
XURALSVDCFXBAX-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C33H35N7O6/c1-8-28(41)38-24-16-22(12-10-18(24)2)37-33-35-17-23(30(34-4)40-33)32(43)39-25-15-21(11-9-19(25)3)36-31(42)20-13-26(44-5)29(46-7)27(14-20)45-6/h8-17H,1H2,2-7H3,(H,36,42)(H,38,41)(H,39,43)(H2,34,35,37,40)
|
|
| Chemical Name |
4-(methylamino)-2-[4-methyl-3-(prop-2-enoylamino)anilino]-N-[2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl]pyrimidine-5-carboxamide
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5983 mL | 7.9914 mL | 15.9829 mL | |
| 5 mM | 0.3197 mL | 1.5983 mL | 3.1966 mL | |
| 10 mM | 0.1598 mL | 0.7991 mL | 1.5983 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.
J Med Chem.2017 Mar 9;60(5):1793-1816. |
|---|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
