| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Microtubules / Tubulin. As a component of the parent molecule, Dolastatin 10, this amide derivative would contribute to the overall activity of the pentapeptide. The mechanism of the parent compound involves high-affinity binding to tubulin at the vinca alkaloid binding site, inhibiting its polymerization into microtubules and causing mitotic arrest.
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| ln Vitro |
As a protected peptide intermediate, this compound itself is not typically biologically evaluated. In the context of the parent pentapeptide, Dolastatin 10 displays extremely potent in vitro cytotoxic activity, with IC50 values in the picomolar to low nanomolar range against a wide range of human cancer cell lines, including those of the lung, breast, and prostate, via the induction of G2/M cell cycle arrest and subsequent apoptosis.
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| ln Vivo |
Dolastatin 10 has demonstrated significant in vivo anti-tumor activity in various murine xenograft models, leading to tumor growth inhibition and, in some studies, partial regression. However, its clinical advancement was limited by significant toxicity, including severe myelosuppression and cumulative peripheral neuropathy, which is common to many anti-tubulin agents.
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| Enzyme Assay |
Standard non-cellular assays for the parent peptide involve measuring its effect on tubulin polymerization kinetics. Purified bovine brain tubulin is incubated with the test compound in the presence of GTP at 37degC. The optical density at 340 nm (OD340) is monitored over time, and the concentration required to inhibit 50% of the rate of tubulin polymerization (IC50) is calculated. The binding constant (Kd) to tubulin can also be measured using a fluorescence-based displacement assay.
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| Cell Assay |
In vitro cytotoxicity assays (e.g., MTS, CellTiter-Glo) are performed on human cancer cell lines (e.g., HeLa, A549, or MDA-MB-231). Cells are seeded in 96-well plates and exposed to serial dilutions of the final Dolastatin 10 peptide for 48-96 hours. The number of viable cells is quantified, and the GI50 (50% growth inhibitory concentration) is determined. Flow cytometric analysis of propidium iodide (PI)-stained cells is used to confirm the accumulation of cells in the G2/M phase.
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| Animal Protocol |
The in vivo efficacy of the parent compound, Dolastatin 10, was evaluated in athymic nude mice bearing subcutaneous human tumor xenografts (e.g., LOX melanoma). Mice were treated intraperitoneally or intravenously with the compound at various doses (e.g., 0.1-0.3 mg/kg) on a schedule such as q2d x5 or q4d x3. Tumor volumes were measured serially with digital calipers. Standard endpoints included tumor growth inhibition (TGI) and, in some studies, tumor regression. Body weight was monitored as a measure of compound tolerability.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic parameters for this specific building block are not relevant, as it is not a drug candidate. The PK of its parent drug, Dolastatin 10, has been studied. It exhibits a very short plasma half-life (t1/2) in mice (often <1 hour), a large volume of distribution (Vd), and is rapidly cleared from the circulation. It is also a well-characterized substrate for the P-glycoprotein (P-gp) efflux pump, which leads to drug resistance.
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| Toxicity/Toxicokinetics |
The toxicology of the parent compound, Dolastatin 10, has been defined preclinically. Its dose-limiting toxicities (DLTs) are those expected for a highly potent anti-tubulin agent, including myelosuppression (particularly neutropenia) and significant gastrointestinal toxicity. Neurotoxicity, manifesting as peripheral neuropathy, was a cumulative, dose-limiting side effect that has hampered its clinical development.
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| References |
[1]. Almeida W P, et al. An easy and stereoselective synthesis of N-Boc-dolaproine via the Baylis–Hillman reaction[J]. Tetrahedron letters, 2003, 44(5): 937-940.
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| Additional Infomation |
This compound is an essential tool for organic synthesis, specifically for constructing the complex pentapeptide backbone of Dolastatin 10 and its analogs. The final product of these synthesis efforts, Dolastatin 10, is a parent compound of the dolastatin class of cytotoxic agents, which has inspired the development of clinically used antibody-drug conjugates (ADCs) like brentuximab vedotin (which uses an analog, MMAE).
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| Molecular Formula |
C23H36N2O4
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|---|---|
| Appearance |
Light yellow to yellow solid powder
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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