| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Soblidotin targets tubulin, specifically inhibiting tubulin polymerization. As a Dolastatin 10 derivative, it binds to tubulin at the vinca alkaloid binding site, preventing the assembly of microtubules. This disruption of microtubule dynamics leads to cell cycle arrest at the G2/M phase and induction of apoptosis through the mitochondrial pathway. Soblidotin shows activity against P-glycoprotein-overexpressing cell lines and breast cancer resistance protein-positive cells derived from lung cancer PC-6, and is more potent than paclitaxel and docetaxel against these cell lines.
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| ln Vitro |
Tubulin polymerization is inhibited by soblidotin (Auristatin PE), a new synthetic derivative of dolastatin 10. More effective than vincristine, paclitaxel, and docetaxel against p-glycoprotein-overexpressing colon cancer H116 cell lines and breast cancer-resistant protein-positive lung cancer PC-6 cell lines, soblidotin (Auristatin PE) exhibits antitumor activity against these cell lines[1]. As a synthetic analogue of dolastatin 10, soblidotin (Auristatin PE) causes apoptosis that is dependent on caspase-3 and inhibits the proliferation of many tumoral cell types. Auristatin PE, also known as soblidotin, demonstrates antitumoral effectiveness in malignancies resistant to vincristine, docetaxel, and paclitaxel, making it a viable chemotherapeutic option for tumors that do not react to conventional microtubule inhibitors[2].
In vitro studies demonstrate that Soblidotin (Auristatin PE) inhibits the growth of several tumor cell lines and induces caspase-3-dependent apoptosis. The compound inhibits tubulin polymerization, resulting in cell cycle arrest and induction of apoptosis. Soblidotin shows potent activity against P-glycoprotein-overexpressing cell lines and breast cancer resistance protein-positive cells derived from lung cancer PC-6, and is more effective than paclitaxel and docetaxel against these cell lines. The compound's antivascular effects are observed in tumor models overexpressing VEGF. |
| ln Vivo |
Auristatin PE (TZT-1027) administered intravenously has been demonstrated to have antitumor efficacy that is either superior to or comparable to that of reference agents Dolastatin 10, Cisplatin, Vincristine, and 5-Fluorouracil. It has also been shown to potently inhibit the growth of P388 leukemic cells and several solid tumors in mice, as well as to extend the animals' lives. Auristatin PE also causes hemorrhagic necrosis of the tumors in xenograft models by decreasing intratumoral blood perfusion 1 to >24 hours after administration[1]. In tumoral models overexpressing VEGF and in murine colon cancers, auristatin PE (Soblidotin) has antivascular actions, causing an increase in vascular permeability, vessel closure, and extensive bleeding[2]. Auristatin PE (0.5 or 1.0 mg/kg) is administered every 7 days to mice with subcutaneous HT-29 tumors (200 mm3) for a total of four cycles. In these circumstances, the growth of HT-29 xenografts is dose-dependently inhibited by Auristatin PE (TZT-1027). Auristatin PE coadministration has no effect on the inhibition of ERK1/2 phosphorylation produced by PD184352. The number of proliferating cells in tumor sections is significantly reduced 24 hours after the first dose of PD184352 compared to what is visible for tumors treated with a vehicle, according to immunostaining for Ki-67. In HT-29 xenografts, auristatin PE therapy alone increases the number of TUNEL-positive cells by 24 hours in a dose-dependent manner; coadministration with PD184352 amplifies this effect[3].
In vivo studies show that Soblidotin exhibits antivascular effects in tumor models overexpressing VEGF and in murine colon tumors, with increased vascular permeability, vessel closure, and widespread hemorrhage. The compound's ability to inhibit tubulin polymerization leads to antitumor activity in various cancer models. Soblidotin has been investigated as a potential anticancer agent. The compound's activity against drug-resistant cell lines suggests potential for overcoming chemotherapy resistance. Further in vivo studies are warranted. |
| Enzyme Assay |
The in vitro tubulin polymerization assay for Soblidotin involves measuring tubulin polymerization using purified tubulin and a spectrophotometer. Tubulin is incubated with varying concentrations of Soblidotin (0.1 nM-10 μM) and GTP at 37°C. Polymerization is monitored by absorbance at 340 nm over time. IC50 values are calculated from dose-response curves. For cell-based assays, cancer cell lines are treated with Soblidotin and cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated using caspase-3/7 activity assays and Annexin V staining.
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| Cell Assay |
In vitro cellular assays for Soblidotin typically use various cancer cell lines including colon cancer, lung cancer, and drug-resistant cell lines. Cells are cultured in appropriate media and treated with the compound at concentrations of 0.01 nM-10 μM for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or ATP-lite assays. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated using caspase-3/7 activity assays, Annexin V-FITC/PI double staining, and Western blot analysis of PARP cleavage. Microtubule disruption is assessed by immunofluorescence of tubulin. The compound's activity against drug-resistant cell lines is evaluated using P-glycoprotein-overexpressing cells and breast cancer resistance protein-positive cells.
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| Animal Protocol |
Mice Auristatin PE and Vinorelbine are dissolved in 0.05 M
sodium lactate buffer (pH 4.5) and in PBS, respectively. Mice are
treated every 7 d with PD184352 (200 mg/kg) or vehicle by oral
administration (four times per day, every 6 h) and with Auristatin PE
(0.25-2.5 mg/kg), Vinorelbine (5-20 mg/kg), or vehicle by i.v. injection
(once per day, 1 h after the first PD184352 administration). Tumor
volume is measured with digital calipers and calculated according to the
following formula: (longest diameter)×(shortest diameter)2/2. Body
weight, tumor volume, and toxicities are noted every 2 to 4 d for the
duration of the experiment. [3] |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Soblidotin are not extensively reported. The compound has a molecular weight of 722.0 and molecular formula of C39H67N5O6. It is a peptide-like compound derived from Dolastatin 10. The compound should be stored at -20°C for long-term preservation. After intravenous administration, the compound reaches systemic circulation and distributes to tissues including tumors. The duration of antitumor activity is consistent with the compound's half-life. Further studies on plasma half-life, clearance, and tissue distribution are needed.
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| Toxicity/Toxicokinetics |
Toxicological data for Soblidotin is not extensively reported. As a tubulin polymerization inhibitor, the compound may have effects on rapidly dividing cells including bone marrow and gastrointestinal epithelium. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, specialized toxicological studies would need to be performed.
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| References |
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| Additional Infomation |
Soblidotin is a tetrapeptide derivative of doralastatin-10. It is a microtubule polymerization inhibitor with potent antitumor activity. It functions as a microtubule destabilizer, antitumor agent, and apoptosis inducer. Its function is associated with 2-phenylethylamine and L-valine. Soblidotin has been used in clinical trials investigating the treatment of sarcoma, lung cancer, and certain adult solid tumors (protocol-specific). Soblidotin is a derivative of doralastatin-10. Soblidotin inhibits microtubule polymerization, leading to cell cycle arrest and apoptosis. (NCI04)
Soblidotin (Auristatin PE, TZT-1027) is a research compound with CAS number 149606-27-9. Its molecular formula is C39H67N5O6 and molecular weight is 722.0. The compound is a novel synthetic Dolastatin 10 derivative that inhibits tubulin polymerization. It induces cell cycle arrest and apoptosis. It shows activity against drug-resistant cell lines and exhibits antivascular effects. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only. |
| Molecular Formula |
C39H67N5O6
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|---|---|
| Molecular Weight |
701.99
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| Exact Mass |
701.509
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| CAS # |
149606-27-9
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| PubChem CID |
6918315
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| Appearance |
White to off-white solid powder
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| Vapour Pressure |
1.1E-28mmHg at 25°C
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| LogP |
4.712
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
50
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
8
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| SMILES |
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)NCCC2=CC=CC=C2)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
|
| InChi Key |
DZMVCVHATYROOS-ZBFGKEHZSA-N
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| InChi Code |
InChI=1S/C39H67N5O6/c1-13-27(6)35(43(10)39(48)33(25(2)3)41-38(47)34(26(4)5)42(8)9)31(49-11)24-32(45)44-23-17-20-30(44)36(50-12)28(7)37(46)40-22-21-29-18-15-14-16-19-29/h14-16,18-19,25-28,30-31,33-36H,13,17,20-24H2,1-12H3,(H,40,46)(H,41,47)/t27-,28+,30-,31+,33-,34-,35-,36+/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-(2-phenylethylamino)propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide
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| Synonyms |
TZT 1027 TZT-1027 Soblidotin
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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: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 : ~100 mg/mL (~142.45 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.56 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4245 mL | 7.1226 mL | 14.2452 mL | |
| 5 mM | 0.2849 mL | 1.4245 mL | 2.8490 mL | |
| 10 mM | 0.1425 mL | 0.7123 mL | 1.4245 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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