Soblidotin (Auristatin PE)
(Synonyms: Auristatin PE; TZT-1027) 目录号 : GC32935
Soblidotin (Auristatin PE) (Auristatin PE) 是一种新型合成的 Dolastatin 10 衍生物和微管蛋白聚合抑制剂。
Cas No.:149606-27-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Mice[3]Soblidotin (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. |
References: [1]. Yamamoto N, et al. Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeks. Cancer Sci. 2009 Feb;100(2):316-21. | |
Soblidotin (Auristatin PE) is a novel synthetic Dolastatin 10 derivative and inhibitor of tubulin polymerization.
Soblidotin (Auristatin PE) is a novel synthetic dolastatin 10 derivative that inhibits tubulin polymerization. Soblidotin (Auristatin PE) exhibits antitumor activity against p-glycoprotein-overexpressing cell lines established from colon cancer H116 and breast cancer-resistant protein-positive cell lines established from lung cancer PC-6, and is more potent than Vincristine, Paclitaxel, and Docetaxel against these cell lines[1]. Soblidotin (Auristatin PE) is a synthetic analog of dolastatin 10 which inhibits the growth of several tumoral cell lines and induces caspase-3-dependent apoptosis. Soblidotin (Auristatin PE) also shows antitumoral activity in Vincristine-, Docetaxel-, and Paclitaxel-resistant tumors, which makes it a potential chemotherapy drug for use in tumors which do not respond to other microtubule inhibitors[2].
Intravenous injection of Auristatin PE (TZT-1027) has been shown to potently inhibit the growth of P388 leukemic cells and several solid tumors in mice, and to prolong the survival of the animals, and its antitumor efficacy has been shown to be superior or comparable to that of the reference agents Dolastatin 10, Cisplatin, Vincristine, and 5-Fluorouracil. Furthermore, in xenograft models, Auristatin PE reduces intratumoral blood perfusion 1 to >24 h after its administration, thereby producing hemorrhagic necrosis of the tumors[1]. Auristatin PE (Soblidotin) shows antivascular effects in tumoral models overexpressing VEGF and in murine colon tumors, with an increase in vascular permeability, vessel closure, and widespread hemorrhage[2]. Mice bearing subcutaneous HT-29 tumors (200 mm3) are dosed every 7 days with Auristatin PE (0.5 or 1.0 mg/kg) for a total of four cycles. Under such conditions, Auristatin PE (TZT-1027) inhibits the growth of HT-29 xenografts in a dose-dependent manner. Coadministration of Auristatin PE does not interfere with the PD184352-induced suppression of ERK1/2 phosphorylation. Immunostaining for Ki-67 as a marker for proliferating cells confirmed that the number of such cells in tumor sections is decreased greatly at 24 hours after the initial dosing with PD184352 compared with that apparent for vehicle-treated tumors. Auristatin PE treatment alone increases the number of TUNEL-positive cells in HT-29 xenografts by 24 hours in a dose-dependent manner, and this effect is enhanced by coadministration of PD184352[3].
[1]. Yamamoto N, et al. Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeks. Cancer Sci. 2009 Feb;100(2):316-21. [2]. Fanale D, et al. Stabilizing versus destabilizing the microtubules: a double-edge sword for an effective cancer treatment option? Anal Cell Pathol (Amst). 2015;2015:690916. [3]. Watanabe K, et al. Blockade of the extracellular signal-regulated kinase pathway enhances the therapeutic efficacy of microtubule-destabilizing agents in human tumor xenograft models. Clin Cancer Res. 2010 Feb 15;16(4):1170-8.
| Cas No. | 149606-27-9 | SDF | |
| 别名 | Auristatin PE; TZT-1027 | ||
| Canonical SMILES | O=C(N[C@@H](C(C)C)C(N([C@@H]([C@H](CC)C)[C@H](OC)CC(N1CCC[C@@]1([H])[C@H](OC)[C@@H](C)C(NCCC2=CC=CC=C2)=O)=O)C)=O)[C@H](C(C)C)N(C)C | ||
| 分子式 | C39H67N5O6 | 分子量 | 701.98 |
| 溶解度 | Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4245 mL | 7.1227 mL | 14.2454 mL |
| 5 mM | 0.2849 mL | 1.4245 mL | 2.8491 mL |
| 10 mM | 0.1425 mL | 0.7123 mL | 1.4245 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Loading Auristatin PE onto boron nitride nanotubes and their effects on the apoptosis of Hep G2 cells
Colloids Surf B Biointerfaces 2019 Sep 1;181:305-314.PMID:31154141DOI:10.1016/j.colsurfb.2019.05.047.
Auristatin PE (PE) as an anti-microtubule agent possesses good anticancer activity. However, the poor target effect and strong side effect limit the clinical application of PE. Boron nitride nanotubes (BNNTs) represent an outstanding carrier candidate providing a wise choice for liver-targeted drug delivery. A drug delivery system based on BNNTs and PE (BNNTs-PE) against liver cancer cells was designed and constructed in this study. Firstly, BNNTs were prepared and hydroxylated, subsequently, PE was loaded onto BNNTs by noncovalent conjugation and was stable at neutral pH but released at pH 4.49. It was found that BNNTs-PE demonstrates an enhanced anticancer activity against Hep G2 cells in comparison with free PE. BNNTs-PE kills cancer cells in a manner of mitochondria-mediated apoptosis pathway through reducing the mitochondrial membrane potential, activating caspase cascade. This BNNTs-PE system may be very promising for the treatment of liver cancer in the future.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2004 Jan-Feb;26(1):53-84.PMID:14988742doi
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, Ad5-FGF4, adeno-Interferon gamma, AE-941, AERx, alemtuzumab, alicaforsen sodium, almotriptan, alpharadin, anakinra, anatumomab mafenatox, ANG-453, anti-CTLA-4 Mab, AP-12009, aprepitant, aripiprazole, arsenic trioxide, astemizole, atlizumab, atomoxetine hydrochloride; Bevacizumab, BG-9928, BMS-188667, botulinum toxin type B, BufferGel; Caffeine, CDP-870, cetuximab, cilomilast, ciluprevir, clofarabine, continuous erythropoiesis receptor activator, CP-461; Darbepoetin alfa, deferasirox, desloratadine, desoxyepothilone B, diflomotecan, dolasetron, drotrecogin alfa (activated), duloxetine hydrochloride; ED-71, efalizumab, efaproxiral sodium, EKB-569, eletriptan, EMD-72000, enfuvirtide, erlotinib hydrochloride, escitalopram oxalate, etoricoxib; Fampridine, ferumoxytol, fondaparinux sodium; Gadofosveset sodium, gastrazole, gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride glutamine; hLM609, HSPPC-96, human insulin; IDD-1, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; Keratinocyte growth factor; Lapatinib, laquinimod, LDP-02, LE-SN38, levetiracetam, levosimendan, licofelone, liposomal doxorubicin, liposomal NDDP, lopinavir, lumiracoxib, LY-156735; Morphine hydrochloride, morphine-6-glucuronide, motexafin gadolinium, MS-27-275, MVA-5T4, MVA-Muc1-IL-2; Nemifitide ditriflutate, neridronic acid nitronaproxen, NSC-683864, NSC-703940, NVP-LAF-237; Oblimersen sodium, ocinaplon, oncomyc-NG, OPC-28326, ortataxel, ospemifene; Palonosetron hydrochloride, PEG-filgrastim peginterferon alfa-2(a), peginterferon alfa-2b, pegsunercept, pemetrexed disodium, pregabalin, prilocaine, pyridoxamine; RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, recombinant human ApoA-I milano/phospholipid complex; SB-715992, Soblidotin, sodium dichloroacetate, St. John's Wort extract; TAS-102, terfenadine, TG-1024, TG-5001, 4'-Thio-ara-C, tipranavir, topixantrone hydrochloride, trabectedin, transdermal selegiline, trimethoprim, troxacitabine, TT-232; Vatalanib succinate, vinflunine; Ximelagatran; Ziprasidone hydrochloride, Zoledronic acid monohydrate.
A new tubulin polymerization inhibitor, Auristatin PE, induces tumor regression in a human Waldenstrom's macroglobulinemia xenograft model
Int J Oncol 1999 Aug;15(2):367-72.PMID:10402249DOI:10.3892/ijo.15.2.367.
Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the anti-tumor effects of Auristatin PE (a structural modification of the marine, shell-less mollusk peptide constituent dolastatin 10). WSU-WM cells were cultured in RPMI-1640 at a concentration of 2x10(5) cells/ml using 24-well plates. Auristatin PE or dolastatin 10 were added to triplicate wells and cell count and viability were assessed after 24, 48 and 72 h. Results showed that both agents were active against WSU-WM, and were able to induce complete growth inhibition at 100 pg/ml. The efficacy of these agents in vivo was evaluated using the WSU-WM SCID mouse xenograft model. Auristatin PE and dolastatin 10 were given i.v. via tail vein at 2.0 mg/kg and 0.2 mg/kg, respectively. The agents were given every second day for three injections which represent the maximum tolerated doses. Tumor growth inhibition (T/C), tumor growth delay (T-C), and log10 kill for Auristatin PE and dolastatin 10 were 0%, 18 days, 2.83 and 67%, 2 days, 0.06, respectively. Based on these animal results, dolastatin 10 was inactive while Auristatin PE was highly active. We therefore focused further investigation on Auristatin PE to understand some of its mechanisms of action. Using two flow cytometry assays, propidium iodide for cell cycle analysis and 7-amino actinomycin D (7AAD) to detect apoptosis, we were able to demonstrate that Auristatin PE at 10 pg/ml after 24 h arrested 50% of WSU-MW cells in G2M. Concomitantly, 31% of auristatin PE-treated cells entered apoptosis. By 72 h, greater than 75% of the cells became apoptotic. The activity of Auristatin PE should be evaluated in other tumor types and in clinical trials.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2004 Sep;26(7):587-612.PMID:15538546doi
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, Soblidotin, squalamine; Telmisartan/hydrochlorothiazide, testosterone gel, TF(c)-KLH conjugate vaccine, TH-9507, theraloc, tipifarnib, tocilizumab, travoprost; ValboroPro, valdecoxib, veglin, voriconazole; Ximelagatran.
Successful treatment of human chronic lymphocytic leukemia xenografts with combination biological agents Auristatin PE and bryostatin 1
Clin Cancer Res 1998 May;4(5):1337-43.PMID:9607595doi
We tested the activity of dolastatin 10 (a natural product derived from the shell-less marine mollusk, Dolabella auricularia, a sea hare) and its structural modification, Auristatin PE, alone and in combination with bryostatin 1 (a protein kinase C activator derived from the marine bryozoan Bugula neritina) on a human B-cell chronic lymphocytic leukemia cell line (WSU-CLL) and in a severe combined immune deficient (SCID) mouse xenograft model bearing this cell line. WSU-CLL cells were cultured in RPMI 1640 at a concentration of 2 x 10(5)/ml using a 24-well plate. Agents were added to triplicate wells, and cell count, viability, mitosis, and apoptosis were assessed after 24 h of incubation at 37 degrees C. Results showed that dolastatin 10 had no apparent inhibition of cell growth at concentrations less than 500 pg/ml. Auristatin PE, on the other hand, showed significant growth inhibition at concentrations as low as 50 pg/ml. Auristatin PE-treated cultures, at this concentration, exhibited 27 and 4.5% mitosis and apoptosis, respectively. Dolastatin 10, at the same concentration, did not exert any effect and was comparable with that of control cultures. In the WSU-CLL-SCID mouse xenograft model, the efficacy of these agents alone and in combination with bryostatin 1 was evaluated. Tumor growth inhibition (T/C), tumor growth delay (T-C), and log10 kill for dolastatin 10, Auristatin PE, and bryostatin 1 were 14%, 25 days, and 1.98; 2%, 25 days, and 1.98; 19%, 13 days, and 1.03, respectively. Auristatin-PE produced cure in three of five mice, whereas dolastatin 10 showed activity but no cures. When given in combination, Auristatin PE + bryostatin 1-treated animals were all free of tumors (five of five) for 150 days and were considered cured. Dolastatin 10 + bryostatin 1-treated animals produced cure in only two of five mice. We conclude that: (a) auristatin-PE is more effective in this model than dolastatin 10; (b) Auristatin PE can be administered at a concentration 10 times greater than dolastatin 10; (c) there is a synergetic effect between these agents and bryostatin 1, which is more apparent in the bryostatin 1 + Auristatin PE combination. The use of these agents should be explored clinically in the treatment of CLL.