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Soblidotin (TZT1027; TZT-1027) is a dolastatin-10 analog that acts as an inhibitor of tubulin polymerization, leading to cell cycle arrest and induction of apoptosis. TZT-1027 showed increased antitumor activity when combined with gemcitabine in animal models.
| 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].
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| 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].
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| Additional Infomation |
Soblidotin is a tetrapeptide derivative of dolastatin 10. It is an inhibitor of tubulin polymerization which exhibits potent antitumor activity. It has a role as a microtubule-destabilising agent, an antineoplastic agent and an apoptosis inducer. It is functionally related to a 2-phenylethylamine and a L-valine.
Soblidotin has been used in trials studying the treatment of Sarcoma, Lung Cancer, and Unspecified Adult Solid Tumor, Protocol Specific. Soblidotin is a dolastatin-10 derivative. Soblidotin inhibits tubulin polymerization, resulting in cell cycle arrest and induction of apoptosis. (NCI04) |
| 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
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| 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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