| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
ALK^{WT} (IC₅₀ = 2.1 nM), ROS1^{WT} (IC₅₀ = 2.3 nM), ALK^{L1196M} (IC₅₀ = 1.3 nM), ALK^{G1202R} (IC₅₀ = 3.9 nM) [1]
|
|---|---|
| ln Vitro |
F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-positive HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers.
1. Enzymatic activity: F-1 exhibited potent inhibitory effects on ALK^{WT}, ROS1^{WT}, ALK^{L1196M} and ALK^{G1202R} kinases with IC₅₀ values of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, respectively, and its inhibitory activity was superior to that of crizotinib and ceritinib [1] 2. Cytotoxicity: F-1 showed significant cytotoxicity against ALK-addicted Karpas299, H2228, Ba/F3 cells expressing G1202R mutant, as well as ROS1-positive HCC78 cells, with IC₅₀ values ranging from 10 nM to 43 nM [1] 3. Cellular signaling and apoptosis: In Karpas-299 cells, F-1 suppressed phospho-ALK and its downstream signaling pathways in a dose-dependent manner, and ultimately induced cell apoptosis in a dose-dependent manner [1] |
| Enzyme Assay |
1. A series of novel 2,4-diarylaminopyrimidine analogues incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs were designed and synthesized to identify ALK/ROS1 dual inhibitors against drug-resistant mutants. Enzymatic assays were conducted to evaluate the inhibitory activity of the synthesized compounds against ALK^{WT}, ROS1^{WT}, ALK^{L1196M} and ALK^{G1202R} kinases, and the IC₅₀ values of F-1 for these kinases were determined and compared with those of crizotinib and ceritinib [1]
|
| Cell Assay |
1. Cytotoxicity assay: ALK-addicted cell lines (Karpas299, H2228), Ba/F3 cells expressing ALK^{G1202R} mutant and ROS1-positive HCC78 cells were used to assess the cytotoxicity of F-1. The cells were treated with different concentrations of F-1, and the cell viability was detected to calculate the IC₅₀ values of F-1 for these cell lines [1]
2. Western blot and apoptosis assay: Karpas-299 cells were treated with F-1 at different doses. Western blot was performed to detect the expression level of phospho-ALK and its downstream signaling molecules, and apoptosis assays were carried out to evaluate the apoptotic effect of F-1 on Karpas-299 cells and the dose-dependent relationship [1] |
| References | |
| Additional Infomation |
1. F-1 was selected from a series of novel 2,4-diarylaminopyrimidine analogs designed and synthesized by introducing a 2-alkoxy-6-alicyclic aminopyridine group, with the aim of finding dual ALK and ROS1 inhibitors resistant to secondary ALK mutations, particularly the "gatekeeper" L1196M mutation and the ceritinib-resistant G1202R mutation.[1] 2. F-1 has been shown to be a promising dual ALK/ROS1 inhibitor with great potential for treating cancers carrying the G1202R ALK mutation.[1]
|
| Molecular Formula |
C22H27CLN8O3S
|
|---|---|
| Molecular Weight |
519.019581079483
|
| CAS # |
2244775-31-1
|
| PubChem CID |
138454747
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
35
|
| Complexity |
766
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=NC(=NC=1NC1C=CC=CC=1NS(C)(=O)=O)NC1=C(N=C(C=C1)N1CCN(C)CC1)OC
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~125 mg/mL (~240.84 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.01 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 20.8 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: 2.08 mg/mL (4.01 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9267 mL | 9.6335 mL | 19.2671 mL | |
| 5 mM | 0.3853 mL | 1.9267 mL | 3.8534 mL | |
| 10 mM | 0.1927 mL | 0.9634 mL | 1.9267 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
