| Size | Price | Stock | Qty |
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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%
Zorifertinib (formerly AZD3759; AZD-3759; zorifertinibum) is a novel, potent, orally bioavailable, CNS (central nervous system)-penetrant EGFR (epidermal growth factor receptor) inhibitor with potential antitumor activity. With IC50 values of 0.3 nM, 0.2 nM, and 0.2 nM, respectively, it inhibits EGFR (WT), EGFR (L858R), and EGFR (exon 19Del). AZD3759 binds to EGFR and certain EGFR mutants, inhibiting their activity. This inhibits EGFR-mediated signaling and may cause EGFR-overexpressing cells to undergo both programmed cell death and tumor growth inhibition. To summarize, AZD3759 is an anticaner medication under investigation that is presently undergoing a Phase 1 clinical trial. It exhibits exceptional penetration of the central nervous system and causes a significant regression of brain metastases in a mouse model.
| Targets |
EGFR (IC50 = 0.3 nM); EGFRL858R (IC50 = 0.2 nM); EGFRExon 19 deletion (IC50 = 0.2 nM)
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| ln Vitro |
AZD3759 inhibits EGFR phosphorylation in H3255 (L858R) cells at an IC50 of 7.2 nM. With an IC50 of 7.7 nM and 7 nM, respectively, AZD3759 exhibits mo activity on H838 cell proliferation as well as inhibitory effects on the pEGFR pathway and cell proliferation of EGFR mutation-derived cells PC-9 and H3255.[1]
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| ln Vivo |
AZD3759 penetrates the monkey brain deeply and exhibits good oral bioavailability in dogs. AZD3759 (15 mg/kg) significantly increases the antitumor efficacy in a dose-dependent manner in a brain metastasis PC-9 (Exon19Del) model.[1]
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| Enzyme Assay |
Following the manufacturer's instructions, the CisBio homogenous time resolved fluorescence approach (HTRF, Cat. No. 62TK0PEJ) is used to evaluate the inhibitory potency of compounds against EGFR WT and mutant enzymes. The assay employs the following final enzyme concentrations: 0.1 nM, 0.03 nM, and 0.026 nM for EGFR wild type, L858R, and Exon19Del, respectively. The corresponding Km values of EGFR enzymes are applied to 0.8 μM, 4 μM, and 25 μM ATP. In summary, 384-well Greiner white polystyrene assay plates are incubated with 3 μL of ATP and 2 μM TK biotin-peptide substrate at room temperature, either with or without a serially diluted compound. The assay buffer includes 1 mM DTT, 5 mM MgCl2, 1 mM MnCl2, and 0.01% CHAPS. The reaction is started by adding 3 μL kinase, which has the ability to phosphorylate the substrate peptide. Once the reaction has been incubated for 30 minutes, it is stopped by adding 6 μl of a detection reagent mix that contains diluted TK Ab Europium Cryptate in detection buffer and 250 nM Strep-XL665. After giving the plates a one-hour incubation period, the EnVision Multilabel Reader from Perkin Elmer is used to measure the fluorescence at 615 and 665 nm, respectively, with an excitation wavelength of 320 nm and standard HTRF settings. The kinase activity is inversely correlated with the calculated signal ratio of 665 to 615 nanometers. The four-parameter logistic fit method is used to determine the concentration of compound that results in 50% inhibition of the corresponding kinase (IC50).
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| Cell Assay |
MTS techniques are used to determine the results of the cell proliferation test. In summary, cells are plated in 96-well plates at a density that permits logarithmic growth throughout the 72-hour experiment, and they are then incubated at 37 °C and 5% CO2 for the entire night. Following that, compounds with concentrations ranging from 30 to 0.0003 mM are exposed to cells for a duration of 72 hours. The CellTiter AQueous Non-Radioactive Cell Proliferation Assay reagent is used to measure cell proliferation for the MTS endpoint in compliance with the manufacturer's protocol. A Tecan Ultra device is used to measure absorbance. Predose measurements are performed, and absorbance readings are used to calculate the concentration required to limit treated cell growth to half that of untreated cells (GI50) values.
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| Animal Protocol |
Rats: Zorifertinib is administered orally to male Han Wistar rats at a dose of 2 mg/kg in 1% methylcellulose. Cerebral spinal fluid (CSF) is extracted from the cisterna magna at 0.25, 0.5, 1, 2, 4, and 7 hours post-dose. Blood samples (>60 μL/time point/each site) are obtained by cardiac puncture, placed into individual EDTA-coagulated tubes, and then promptly diluted with three times the volume of water. After being removed, brain tissue is homogenized in three times the volume of 100 mM phosphate buffered saline (pH7.4). All samples are kept cold until they are analyzed using LC/MS/MS.
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| References |
| Molecular Formula |
C22H23CLFN5O3
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|---|---|
| Molecular Weight |
459.90
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| Exact Mass |
459.15
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| Elemental Analysis |
C, 57.46; H, 5.04; Cl, 7.71; F, 4.13; N, 15.23; O, 10.44
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| CAS # |
1626387-80-1
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| Related CAS # |
Zorifertinib hydrochloride;1626387-81-2
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| Appearance |
white to off-white solid powder
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| SMILES |
C[C@@H]1CN(CCN1C(=O)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC)C
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| InChi Key |
MXDSJQHFFDGFDK-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6,9-10,12-13H,7-8,11H2,1-3H3,(H,25,26,27)/t13-/m1/s1
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| Chemical Name |
[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl] (2R)-2,4-dimethylpiperazine-1-carboxylate
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| Synonyms |
zorifertinibum; zorifertinib; AZD3759; AZD-3759; AZD 3759
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.44 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 (5.44 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 25.0 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: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.44 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1744 mL | 10.8719 mL | 21.7439 mL | |
| 5 mM | 0.4349 mL | 2.1744 mL | 4.3488 mL | |
| 10 mM | 0.2174 mL | 1.0872 mL | 2.1744 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.
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