| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
EGFR[1]
T790M mutant EGFR. As the less active enantiomer, (3S,4S)-PF-06459988 has a significantly reduced ability to bind to and inhibit the T790M mutant EGFR. Its primary research use is as a negative control to confirm target-specific effects. |
|---|---|
| ln Vitro |
(3S,4S)-PF-06459988 is the less active S-enantiomer of the potent T790M EGFR inhibitor PF-06459988. Its activity against the T790M mutant EGFR is significantly lower than that of the active enantiomer. It exhibits a minimally reactive electrophile, reducing off-target labeling, but its potency is decreased.
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| ln Vivo |
No specific in vivo activity is reported for this enantiomer. As a negative control, it may be used in xenograft studies to confirm that the anti-tumor activity of the parent compound is due to specific EGFR inhibition. It is not expected to have significant efficacy in vivo at doses where the active enantiomer is effective.
|
| Enzyme Assay |
Cell-free T790M mutant EGFR kinase assays are performed using the recombinant enzyme. (3S,4S)-PF-06459988 is incubated with the enzyme and a peptide substrate in the presence of ATP. Kinase activity is measured, and the IC50 is calculated. This value is compared to the highly potent IC50 of the active enantiomer to confirm its reduced activity.
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| Cell Assay |
T790M EGFR-mutant NSCLC cell lines are seeded in 96-well plates. Cells are treated with the (3S,4S) enantiomer in parallel with the active enantiomer. Cell viability is assessed by MTT assay. The lack of effect on cell viability and EGFR phosphorylation by the (3S,4S) enantiomer at the active enantiomer's IC50 concentration confirms its use as a control.
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| Animal Protocol |
(3S,4S)-PF-06459988 can be administered as a negative control in mouse xenograft models of T790M mutant NSCLC. It would be dosed identically to the active enantiomer (e.g., 10 mg/kg, oral). Tumor volumes in the control group will shrink significantly less or not at all compared to the active drug group, validating the target mechanism.
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| ADME/Pharmacokinetics |
The pharmacokinetics of (3S,4S)-PF-06459988 are similar to those of the active enantiomer, as they are chemically similar. However, its PK profile is not the focus, as its primary use is as a control. It is soluble in DMSO for in vitro use. For in vivo studies, it is formulated in a vehicle like 0.5% methylcellulose.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for this compound. As the less active enantiomer, it is expected to be less potent and therefore less toxic than the active enantiomer. It is used in research to confirm that the observed effects are due to target inhibition rather than off-target toxicity. It is not a therapeutic agent.
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| 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. Journal of Medicinal Chemistry, 59(5), 2005–2024.
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| Additional Infomation |
Other information: (3S,4S)-PF-06459988 (CAS 1858291-14-1) is a research-grade chemical, not an FDA-approved drug. It is the less active S-enantiomer of PF-06459988, a potent T790M mutant EGFR inhibitor. It is used as a negative control to study EGFR-dependent resistance mechanisms. For research use only.
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| Molecular Formula |
C19H22CLN7O3
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|---|---|
| Molecular Weight |
431.88
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| Exact Mass |
431.147
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| CAS # |
1858291-14-1
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| Related CAS # |
PF-06459988;1428774-45-1
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| PubChem CID |
127030086
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
629
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1C=C(C=N1)NC2=NC3=C(C(=CN3)Cl)C(=N2)OC[C@@H]4CN(C[C@H]4OC)C(=O)C=C
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| InChi Key |
ODMXWZROLKITMS-SMDDNHRTSA-N
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| InChi Code |
InChI=1S/C19H22ClN7O3/c1-4-15(28)27-7-11(14(9-27)29-3)10-30-18-16-13(20)6-21-17(16)24-19(25-18)23-12-5-22-26(2)8-12/h4-6,8,11,14H,1,7,9-10H2,2-3H3,(H2,21,23,24,25)/t11-,14+/m0/s1
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| Chemical Name |
1-[(3S,4S)-3-[[5-chloro-2-[(1-methylpyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxymethyl]-4-methoxypyrrolidin-1-yl]prop-2-en-1-one
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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) |
DMSO: 50 mg/mL (115.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 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 (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3155 mL | 11.5773 mL | 23.1546 mL | |
| 5 mM | 0.4631 mL | 2.3155 mL | 4.6309 mL | |
| 10 mM | 0.2315 mL | 1.1577 mL | 2.3155 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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