| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The direct molecular target of Dolastatin 10 trifluoroacetate is tubulin. It is an antimitotic agent that binds with high affinity, in a noncompetitive manner, to the vinca alkaloid binding domain on β-tubulin. The inhibition constant (Ki) for this binding is 1.4 μM. This binding inhibits the polymerization of tubulin into microtubules and induces tubulin aggregation in vitro.
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|---|---|
| ln Vitro |
In vitro, Dolastatin 10 is a potent inhibitor of tubulin polymerization, with a half-maximal inhibitory concentration (IC₅₀) of approximately 1.2 μM. At the cellular level, it exhibits extremely potent growth inhibitory activity against a broad panel of human tumor cell lines. For instance, its IC₅₀ values against various human leukemia, lymphoma, and solid tumor cell lines (e.g., OVCAR-3 and NSCLC) range from 0.1 nM to 10 nM. Its mechanism of action involves arresting the cell cycle at the G2/M phase by disrupting microtubule dynamics, ultimately inducing apoptosis.
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| ln Vivo |
In vivo, Dolastatin 10 has been evaluated in clinical studies involving patients with various advanced solid tumors. However, it demonstrated limited efficacy in Phase II clinical trials. In patients with advanced breast cancer (21 patients), only one partial response was observed (response rate 5%), with four patients achieving stable disease. In patients with hormone-refractory prostate cancer (16 patients), no objective responses were observed, and three patients (20%) had stable disease. These results halted its further clinical development as a single agent.
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| Enzyme Assay |
Binding affinity is assessed using purified tubulin via a tubulin polymerization assay or a competitive binding assay. Purified porcine brain tubulin (typically 1 mg/mL) is incubated with varying concentrations of Dolastatin 10 (e.g., 0 to 10 µM) in a glutamate-containing buffer at 37°C. Polymerization is followed by monitoring the increase in absorbance at 350 nm. Dolastatin 10 inhibits polymerization in a concentration-dependent manner with an IC₅₀ of approximately 1.2 µM. Alternatively, a competitive binding assay using radiolabeled vincristine ([³H]-vincristine) incubated with tubulin can be used, where Dolastatin 10 noncompetitively inhibits this binding with a Ki value of 1.4 µM.
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| Cell Assay |
Cytotoxicity is determined using standard cell proliferation assays. Tumor cells (e.g., L1210 leukemia cells or OVCAR-3 ovarian cancer cells) are seeded in 96-well plates (e.g., 5×10³ cells per well) and allowed to adhere overnight in a 37°C, 5% CO₂ incubator. The next day, the old medium is replaced with fresh medium containing escalating concentrations of Dolastatin 10 (e.g., from 0.001 nM to 100 nM) and incubated for 48 to 96 hours. After incubation, viable cells are quantified by adding MTT or CCK-8 reagent to each well and incubating for 1-4 hours at 37°C. Absorbance is measured at a specific wavelength (e.g., 490 nm or 450 nm) using a microplate reader, and IC₅₀ values are calculated by plotting concentration-inhibition curves using software such as GraphPad Prism. A vehicle-treated negative control group and a positive control group (e.g., paclitaxel) are recommended, with 3-6 replicate wells per group to ensure result accuracy.
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| Animal Protocol |
Based on clinical studies of its parent drug Dolastatin 10, the administration schedule is intravenous infusion every 3 weeks. In animal models, to evaluate its antitumor activity, experiments are typically conducted in tumor xenograft mouse models. A specific protocol would involve: subcutaneous implantation of human tumor cells (e.g., human breast or prostate cancer cells) into the right forelimb axilla of immunodeficient mice (e.g., BALB/c nude or NOD-SCID mice). When tumor volumes reach approximately 100-200 mm³, tumor-bearing mice are randomized into groups (n=6-10 per group). Dolastatin 10 is typically administered intravenously via the tail vein at doses ranging from 0.1 to 0.5 mg/kg on an intermittent schedule, such as every 3-4 days for a total of 3-4 doses (e.g., q4d×3 or q4d×4). Tumor volumes (calculated as length × width² / 2) and body weights are measured twice weekly with calipers to assess the tumor growth inhibition rate (TGI%) and drug toxicity.
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| ADME/Pharmacokinetics |
Preclinical pharmacokinetic studies have shown that Dolastatin 10 is stable in plasma for at least 24 hours. Following intravenous injection, its estimated elimination half-life is approximately 5.6 hours. In a Phase I clinical study, pharmacokinetic analysis utilized a limited sampling strategy to estimate drug exposure in patients, which was correlated with toxicity, particularly neurotoxicity. Notably, significant inter-patient variability in plasma clearance has been observed.
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| Toxicity/Toxicokinetics |
The primary dose-limiting toxicity of Dolastatin 10 trifluoroacetate is myelosuppression, particularly granulocytopenia. In Phase II clinical trials for advanced breast and prostate cancers, at a dose of 400 μg/m² administered every three weeks, severe (Grade 3/4) neutropenia was observed. Furthermore, peripheral neuropathy is another significant non-hematological toxicity, which was one of the primary reasons hindering its further clinical development. Dolastatin 10 exhibits a side effect profile similar to that of other antimitotic agents, such as taxanes and vinca alkaloids.
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| References |
[1]. https://pubchem.ncbi.nlm.nih.gov/compound/121513847
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| Molecular Formula |
C44H69F3N6O8S
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|---|---|
| Molecular Weight |
899.114281415939
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| Exact Mass |
898.484
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| CAS # |
2342568-65-2
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| Related CAS # |
110417-88-4
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| PubChem CID |
121513847
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
0
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
62
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| Complexity |
1300
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| Defined Atom Stereocenter Count |
9
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| SMILES |
S1C=CN=C1[C@H](CC1C=CC=CC=1)NC([C@H](C)[C@H]([C@@H]1CCCN1C(C[C@H]([C@H]([C@@H](C)CC)N(C)C([C@H](C(C)C)NC([C@H](C(C)C)N(C)C)=O)=O)OC)=O)OC)=O.FC(C(=O)O)(F)F
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| InChi Key |
AEMLXRTXOFUMAI-WUBDFCFDSA-N
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| InChi Code |
InChI=1S/C42H68N6O6S.C2HF3O2/c1-13-28(6)37(47(10)42(52)35(26(2)3)45-40(51)36(27(4)5)46(8)9)33(53-11)25-34(49)48-22-17-20-32(48)38(54-12)29(7)39(50)44-31(41-43-21-23-55-41)24-30-18-15-14-16-19-30;3-2(4,5)1(6)7/h14-16,18-19,21,23,26-29,31-33,35-38H,13,17,20,22,24-25H2,1-12H3,(H,44,50)(H,45,51);(H,6,7)/t28-,29+,31-,32-,33+,35-,36-,37-,38+;/m0./s1
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| Chemical Name |
(2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide;2,2,2-trifluoroacetic acid
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| Synonyms |
Dolastatin 10 trifluoroacetate; 2342568-65-2; (2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide;2,2,2-trifluoroacetic acid; orb1704640;
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1122 mL | 5.5611 mL | 11.1221 mL | |
| 5 mM | 0.2224 mL | 1.1122 mL | 2.2244 mL | |
| 10 mM | 0.1112 mL | 0.5561 mL | 1.1122 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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