| Size | Price | Stock | Qty |
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| 1g |
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| Other Sizes |
| Targets |
Microtubules / Tubulin. As a component of Dolastatin 10, this amino acid residue contributes to the overall anti-tubulin polymerization activity of the parent pentapeptide. The parent compound, Dolastatin 10, binds to tubulin, specifically at the vinca alkaloid binding site, inhibiting microtubule polymerization and causing mitotic arrest.
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| ln Vitro |
This compound itself is not tested for biological activity as it is an intermediate building block. In the context of the parent molecule, Dolastatin 10, the in vitro activity is extremely potent, with IC50 values in the picomolar to low nanomolar range against a variety of human cancer cell lines, including NCI-H460 lung, HeLa cervical, and LOX melanoma cells.
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| ln Vivo |
Dolastatin 10, the parent pentapeptide containing this residue, has shown profound in vivo anti-tumor efficacy in murine xenograft models, leading to tumor regression in several models (e.g., B16 melanoma, M5076 ovarian sarcoma). However, its clinical development was hindered by severe toxicity, including myelosuppression and peripheral neuropathy.
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| Enzyme Assay |
Standard non-cellular assays for this building block's parent peptide involve measuring its ability to inhibit tubulin polymerization. A typical assay uses purified bovine brain tubulin (1 mg/mL) in a reaction buffer containing GTP and 10% glycerol at 37degC. Various concentrations of the test compound (Dolastatin 10) are added, and the rate of tubulin polymerization is monitored spectrophotometrically by measuring the increase in absorbance (OD340) over time. The IC50 for inhibition of tubulin polymerization is determined.
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| Cell Assay |
Standard cell viability assays (e.g., MTT, CellTiter-Glo) are used to test the final Dolastatin peptide. Human cancer cell lines are seeded in 96-well plates and treated with serial dilutions of the compound for 48-72 hours. Cell viability is measured, and the concentration required to inhibit growth by 50% (GI50) is calculated. For cell cycle analysis, propidium iodide (PI) staining followed by flow cytometry is used to measure the accumulation of cells in the G2/M phase, confirming mitotic arrest.
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| Animal Protocol |
In vivo animal studies for the parent compound, Dolastatin 10, were conducted using murine xenograft models. Nude mice bearing subcutaneous human tumor xenografts (e.g., LOX melanoma) were treated intravenously or intraperitoneally with Dolastatin 10 at various doses and schedules (e.g., q2d x5 or q7d x3). Tumor volumes were measured every few days with calipers, and body weight was monitored as a marker for general toxicity.
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| ADME/Pharmacokinetics |
This compound is an intermediate, so its PK is known via its parent peptide. Dolastatin 10 exhibits a short plasma half-life (t1/2 of ~15-30 minutes in mice) and is extensively distributed into tissues. It is a substrate for P-glycoprotein (P-gp) efflux pumps, which contributes to resistance. The N-Boc-dolaproine-OH dicyclohexylamine intermediate would not be administered for a PK study.
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| Toxicity/Toxicokinetics |
The toxicology of Dolastatin 10 has been well-documented in preclinical studies. Its dose-limiting toxicities (DLTs) are primarily on rapidly dividing tissues, including severe myelosuppression (neutropenia and thrombocytopenia) and gastrointestinal toxicity. Neurotoxicity (peripheral neuropathy) is also a significant, cumulative dose-limiting toxicity that hindered 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 not a drug but a specialized organic synthesis intermediate. It is a key building block for the total synthesis of Dolastatin 10 and its analogs (e.g., MMAE), which are highly potent antimitotic agents. These analogs have been conjugated to antibodies (as ADCs) to improve their therapeutic window. This intermediate is valuable for synthetic chemistry and structure-activity relationship (SAR) studies in the development of peptide-based anticancer agents.
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| Molecular Formula |
C25H46N2O5
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|---|---|
| Related CAS # |
N-Boc-dolaproine-OH ((+)-phenylethylamine)
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| Appearance |
White to off-white 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 |
| 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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