PF-06459988
Based on 1 Customer Validation
PF-06459988 is an orally activity, irreversible and mutant-selective inhibitor of EGFR mutant forms. PF-06459988 demonstrates high potency and specificity to the T790M-containing double mutant EGFRs. PF-06459988 can be used for the research of cancer.
For research use only. We do not sell to patients.
- Purity: 99.10%
- CAS No.: 1428774-45-1
- Formula: C19H22ClN7O3
- Molecular Weight:431.88
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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All EGFR Isoforms
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Biological Activity
IC50: 45 nM (H1975 EGFR), 3.3 μM (EGFR)
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
5100 nM
Compound: 1; PF-06459988
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Inhibition of EGF-stimulated wild type EGFR autophosphorylation expressed in human A549 cells by sandwich ELISA
Inhibition of EGF-stimulated wild type EGFR autophosphorylation expressed in human A549 cells by sandwich ELISA
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[PMID: 26756222] |
| NCI-H1975 | IC50 |
13 nM
Compound: 1; PF-06459988
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Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells after 2 hrs by sandwich ELISA
Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells after 2 hrs by sandwich ELISA
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[PMID: 26756222] |
| PC-9 | IC50 |
140 nM
Compound: 1; PF-06459988
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Inhibition of EGFR deletion mutant autophosphorylation in human PC9 cells after 2 hrs by sandwich ELISA
Inhibition of EGFR deletion mutant autophosphorylation in human PC9 cells after 2 hrs by sandwich ELISA
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[PMID: 26756222] |
PF-06459988 (0-10 μM; 2 h) shows good cellular potency to NSCLC cell lines and high selectivity between the potent target and WT EGFR[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NSCLC cell lines
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Concentration:0-10 μM
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Incubation Time:2 hours
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Result:Exibited excellent cellular potency to H1975 (L858R/T790M), PC9-DRH (Del/T790M), H3255 (L858R), PC9 (Del), HCC827 (Del) and A549 (WT) cell lines with IC50 values of 13, 7, 21, 140, 90 and 5100 nM, respectively. Showed high specificity to T790M-containing double mutan EGFRs.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1428774-45-1
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Appearance Solid
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Molecular Weight 431.88
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Formula C19H22ClN7O3
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Color White to light yellow
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SMILES
C=CC(N1C[C@H](COC2=C3C(NC=C3Cl)=NC(NC4=CN(C)N=C4)=N2)[C@@H](OC)C1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvent & Solubility
DMSO : 50 mg/mL (115.77 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.75 mg/mL (6.37 mM); Clear solution
This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.75 mg/mL (6.37 mM); Clear solution
This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[1]. Cheng H, et al. Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants. J Med Chem. 2016 Mar 10;59(5):2005-24. doi: 10.1021/acs.jmedchem.5b01633. Epub 2016 Jan 28. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3155 mL | 11.5773 mL | 23.1546 mL | 57.8864 mL |
| 5 mM | 0.4631 mL | 2.3155 mL | 4.6309 mL | 11.5773 mL | |
| 10 mM | 0.2315 mL | 1.1577 mL | 2.3155 mL | 5.7886 mL | |
| 15 mM | 0.1544 mL | 0.7718 mL | 1.5436 mL | 3.8591 mL | |
| 20 mM | 0.1158 mL | 0.5789 mL | 1.1577 mL | 2.8943 mL | |
| 25 mM | 0.0926 mL | 0.4631 mL | 0.9262 mL | 2.3155 mL | |
| 30 mM | 0.0772 mL | 0.3859 mL | 0.7718 mL | 1.9295 mL | |
| 40 mM | 0.0579 mL | 0.2894 mL | 0.5789 mL | 1.4472 mL | |
| 50 mM | 0.0463 mL | 0.2315 mL | 0.4631 mL | 1.1577 mL | |
| 60 mM | 0.0386 mL | 0.1930 mL | 0.3859 mL | 0.9648 mL | |
| 80 mM | 0.0289 mL | 0.1447 mL | 0.2894 mL | 0.7236 mL | |
| 100 mM | 0.0232 mL | 0.1158 mL | 0.2315 mL | 0.5789 mL |
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