| 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 potent anti-tubulin polymerization activity of the parent pentapeptide. Dolastatin 10 binds to the vinca alkaloid binding site on tubulin, potently inhibiting the polymerization of tubulin into microtubules, thus arresting cells in the G2/M phase of the cell cycle.
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| ln Vitro |
This compound is an intermediate and not typically tested for biological activity. The parent molecule, Dolastatin 10, has extremely potent in vitro activity with IC50 values in the picomolar to low nanomolar range against a wide panel of human cancer cell lines, such as NCI-H460 (lung), HeLa (cervical), and LOX (melanoma), by inducing G2/M arrest and apoptosis.
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| ln Vivo |
Dolastatin 10 has shown significant in vivo anti-tumor activity in murine xenograft models, including B16 melanoma and M5076 ovarian sarcoma models. At well-tolerated doses, it induced tumor regression in several models. However, severe off-target toxicities (including neutropenia and peripheral neuropathy) hindered its clinical development as a single agent.
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| Enzyme Assay |
Standard non-cellular assays for the parent peptide involve its effect on purified tubulin. Dolastatin 10 is incubated with purified bovine brain tubulin (1 mg/mL) in a reaction buffer containing GTP and 10% glycerol at 37degC. The rate of tubulin polymerization is followed spectroscopically (OD340). The IC50 for inhibition of tubulin polymerization is determined by comparing the rate in the presence of various concentrations of the compound to the control.
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| Cell Assay |
For in vitro cellular assays, human cancer cells are seeded in 96-well plates and treated with serial dilutions of the final Dolastatin 10 peptide for 48-72 hours. The number of viable cells is measured using the MTT or CellTiter-Glo assay to calculate the GI50. To confirm the mechanism of action, cells are fixed with ethanol, stained with propidium iodide, and analyzed by flow cytometry to determine the proportion of cells arrested in the G2/M phase.
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| Animal Protocol |
In vivo efficacy studies for the parent compound (Dolastatin 10) were performed using female athymic nude mice bearing human tumor xenografts (e.g., LOX melanoma). When tumors reached ~100-200 mm3, mice were treated intraperitoneally with Dolastatin 10 at various doses (e.g., 0.1-0.3 mg/kg, q2d for 5 doses). Tumor volumes (length x width2/2) and body weights were measured every 2-3 days. Tumor growth inhibition (TGI) was calculated at the study endpoint.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Dolastatin 10 in mice include a short plasma half-life (t1/2 ~15-30 minutes), a moderate volume of distribution (Vd), and rapid clearance (CL). It is a substrate for the P-glycoprotein (P-gp) efflux transporter, which contributes to its observed multi-drug resistance (MDR) phenotype. The (phenylethylamine) salt form of this intermediate is designed to improve its handling and stability, not its in vivo ADME.
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| Toxicity/Toxicokinetics |
The toxicological profile of Dolastatin 10 has been evaluated in preclinical species. The major dose-limiting toxicities (DLTs) are related to its antimitotic mechanism and include bone marrow suppression (neutropenia, thrombocytopenia) and gastrointestinal disturbances. Additionally, cumulative peripheral neuropathy was a significant side effect that prevented its further clinical development as a conventional chemotherapy agent.
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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 a specialized research tool for synthetic organic and medicinal chemistry. It serves as an advanced intermediate for the total synthesis of Dolastatin 10 and numerous analogs. Due to the high potency of Dolastatin 10 and its derivatives (like MMAE), this building block is particularly important in the field of Antibody-Drug Conjugates (ADCs) for the development of novel, targeted cancer therapies.
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| Molecular Formula |
C21H34N2O5
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|---|---|
| Related CAS # |
N-Boc-dolaproine-OH dicyclohexylamine
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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) |
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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