| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
EGFR-Del19/T790M/C797S triple mutation. CH7233163 is a non-covalent ATP-competitive inhibitor that selectively binds to the ATP-binding pocket of this resistant mutant, blocking its kinase activity.
|
|---|---|
| ln Vitro |
CH7233163 is a potent inhibitor of the EGFR-Del19/T790M/C797S triple mutant with an IC50 of 0.28 nM in biochemical assays. It selectively targets the resistant mutation and effectively blocks EGFR phosphorylation in Del19/T790M/C797S-mutant NIH3T3 cells, demonstrating significant anti-proliferative activity.
|
| ln Vivo |
CH7233163 can overcome Osimertinib-resistant EGFR-Del19/T790M/C797S mutation. In preclinical models, it demonstrates significant antitumor activity. It is a valuable research tool for studying resistance mechanisms in NSCLC and for developing new therapies to combat this clinically challenging drug-resistant mutation.
|
| Enzyme Assay |
Cell-free EGFR kinase assays are performed using recombinant human EGFR-Del19/T790M/C797S triple mutant enzyme. The compound is incubated with the enzyme and a peptide substrate in the presence of ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit. The IC50 of 0.28 nM is calculated.
|
| Cell Assay |
NIH3T3 cells engineered to express the EGFR-Del19/T790M/C797S mutant are seeded in 96-well plates and treated with increasing concentrations of CH7233163 for 72 hours. Cell viability is assessed by the MTT assay. The inhibition of EGFR phosphorylation is measured by Western blot of cell lysates using a phospho-specific antibody.
|
| Animal Protocol |
For in vivo studies, CH7233163 is administered orally to mice bearing xenografts of Del19/T790M/C797S-mutant NIH3T3 cells. Dosing is typically once daily for 2-4 weeks. Tumor volumes are measured with calipers. At study termination, tumors are excised for Western blot analysis of EGFR phosphorylation and for immunohistochemical analysis.
|
| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for CH7233163. It is soluble in DMSO (100 mg/mL). For in vivo studies, it would typically be formulated in a vehicle such as 0.5% methylcellulose. Its half-life, oral bioavailability, and clearance have not been characterized in the literature. It is a research chemical.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported for CH7233163. As a selective EGFR mutant inhibitor, on-target toxicity is expected to be less than that of pan-EGFR inhibitors. Comprehensive toxicological assessments have not been published. The compound is a research chemical and is not intended for human use.
|
| References | |
| Additional Infomation |
Other information: CH7233163 (CAS 2923365-71-1) is a research compound, not FDA-approved. It is a potent, non-covalent, ATP-competitive inhibitor (IC50 = 0.28 nM) of the Osimertinib-resistant EGFR-Del19/T790M/C797S triple mutation. It is a valuable tool for studying drug resistance in NSCLC. For research use only.
|
| Molecular Formula |
C31H34F3N9O3S
|
|---|---|
| Molecular Weight |
669.720374584198
|
| Exact Mass |
669.245
|
| CAS # |
2923365-71-1
|
| PubChem CID |
154701097
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
4.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
47
|
| Complexity |
1180
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)N1C2=CC(=NC=C2C3=C1C=C(C=C3OCC(F)(F)F)N4CCN(CC4)C)NC5=NC(=NC=C5)C6=CN(N=C6)S(=O)(=O)C7CC7
|
| InChi Key |
KMBMYNDPNVGEFI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C31H34F3N9O3S/c1-19(2)43-24-14-28(38-27-6-7-35-30(39-27)20-15-37-42(17-20)47(44,45)22-4-5-22)36-16-23(24)29-25(43)12-21(41-10-8-40(3)9-11-41)13-26(29)46-18-31(32,33)34/h6-7,12-17,19,22H,4-5,8-11,18H2,1-3H3,(H,35,36,38,39)
|
| Chemical Name |
N-[2-(1-cyclopropylsulfonylpyrazol-4-yl)pyrimidin-4-yl]-7-(4-methylpiperazin-1-yl)-5-propan-2-yl-9-(2,2,2-trifluoroethoxy)pyrido[4,3-b]indol-3-amine
|
| 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) |
DMSO: 100 mg/mL (149.32 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4932 mL | 7.4658 mL | 14.9316 mL | |
| 5 mM | 0.2986 mL | 1.4932 mL | 2.9863 mL | |
| 10 mM | 0.1493 mL | 0.7466 mL | 1.4932 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
