| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Auristatin
PF-06380101, the parent compound, targets tubulin, the protein subunit of microtubules. As an Auristatin analog, it binds to the tubulin at the vinca alkaloid binding site, inhibiting tubulin polymerization and disrupting microtubule dynamics. This leads to the arrest of cells in the G2/M phase of the cell cycle and subsequently induces apoptosis. The deuterated version is used as an internal standard for LC-MS/MS analysis and does not have a separate target profile; it is toxic to rapidly dividing cancer cells. PF-06380101 is a potent cytotoxic agent, used as a warhead in ADCs. |
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| ln Vitro |
In vitro, PF-06380101 (the unlabeled parent) is a highly potent tubulin polymerization inhibitor and cytotoxic agent. It causes cell cycle arrest in the G2/M phase and induces apoptosis in various cancer cell lines. The IC50 values are typically in the low picomolar to low nanomolar range, depending on the cell line. As it is a Dolastatin 10 analogue, it has a similar mechanism and potency. The deuterated version is not used for biological activity assessment; rather, it is used as an analytical standard. For the parent compound, the primary activity is the inhibition of tubulin polymerization and the subsequent killing of rapidly dividing cells.
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| ln Vivo |
In vivo, PF-06380101 is a highly potent cytotoxic agent. It is not administered as a free drug due to its narrow therapeutic window. Instead, it is conjugated to a monoclonal antibody to form an antibody-drug conjugate (ADC). As an ADC payload, it is delivered specifically to tumor cells, leading to targeted cell death. The free drug would be expected to have significant systemic toxicity. The deuterated version is used exclusively for analytical purposes in bioanalysis. There are no reports of the deuterated version being administered in vivo as a therapeutic.
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| Enzyme Assay |
PF-06380101-d8 is not used in an enzyme binding assay; it is an internal standard for LC-MS/MS. The analytical method for quantifying PF-06380101 is: A stock solution is prepared in methanol or acetonitrile. For LC-MS/MS, an aliquot of the sample (e.g., 50 uL of plasma) is spiked with a fixed concentration of the internal standard (e.g., 5 ng/mL). The sample is extracted by protein precipitation (e.g., adding 200 uL of acetonitrile), vortexed, and centrifuged. The supernatant is injected onto an LC column. The MS/MS is operated in positive ion mode. The MRM transitions for PF-06380101 are based on its specific parent and fragment ions, while the d8 internal standard has a mass shift of +8 Da. The peak area ratio is used for quantification.
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| Cell Assay |
PF-06380101-d8 is not used in cell-based assays; it is used as a standard in analytical methods. The parent compound, PF-06380101, is a cytotoxic agent. In cell culture, it is used as a positive control for tubulin inhibitors. However, because of its high potency, it is typically not used as a free drug in cell-based assays unless appropriate safety precautions are taken (it is a potent toxin).
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| Animal Protocol |
A typical protocol for an ADC xenograft model involves the antibody-drug conjugate, not the free payload. Mice bearing established tumors (e.g., with a specific antigen) are treated intravenously with the ADC at doses of 1-10 mg/kg (based on antibody content) once weekly for 2-4 weeks. The free payload is not administered due to systemic toxicity. For measuring total antibody-conjugated and free drug in plasma, the d8 version is used as an internal standard.
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| ADME/Pharmacokinetics |
The parent compound is cytotoxic, and its PK is not typically studied free. The ADC's PK is dominated by the antibody, with a long half-life (days).
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| Toxicity/Toxicokinetics |
PF-06380101 is highly cytotoxic. It is a potent tubulin inhibitor and would cause significant toxicity (e.g., bone marrow suppression, peripheral neuropathy, gastrointestinal toxicity) if administered systemically as a free drug. As an ADC payload, the toxicity is reduced. The d8 version is not used in toxicity studies.
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| References | |
| Additional Infomation |
PF-06380101-d8 is a research-grade stable isotope-labeled compound used as an internal standard in LC-MS/MS methods for the quantification of PF-06380101, an Auristatin microtubule inhibitor and cytotoxic Dolastatin 10 analogue. It is not approved for clinical use. This product is for research use only. Store as a solid at -20degC, protected from light and moisture.
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| Molecular Formula |
C39H54D8N6O6S
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|---|---|
| Related CAS # |
PF-06380101;1436391-86-4
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| Appearance |
Typically exists as solid at room temperature
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~35 mg/mL (~46.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.33 mg/mL (3.10 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 23.3 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: ≥ 2.33 mg/mL (3.10 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 23.3 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: ≥ 2.33 mg/mL (3.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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