Edotecarin (J 107088)
(Synonyms: J 107088; PF 804950) 目录号 : GC33128
Edotecarin (J 107088) 是一种有效的拓扑异构酶 I 抑制剂，可诱导单链 DNA 切割，IC50 为 50 nM。
Cas No.:174402-32-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Edotecarin is a potent inhibitor of topoisomerase I that can induces single-strand DNA cleavage, with IC50 of 50 nM.
In the presence of human colon cancer cells labeled with 3Hthymidine, edotecarin (0.6 μmol/L) increases the formation of DNA-protein complexes in a time-dependent manner[1].
Edotecarin produces an 83% increase in survival in mice bearing intracranial D-456MG glioma and shows a strong antimetastatic effect[1]. Edotecarin results in tumor growth delays ranging from 10.45 days at the lowest dose (3 mg/kg) to 24.83 days at the highest (100 mg/kg). Combination treatment of edotecarin plus irinotecan improves antitumor activity in vivo compared with either agent alone[2].
[1]. Saif MW, et al. Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. [2]. Ciomei M, et al. Antitumor efficacy of edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model. Clin Cancer Res. 2006 May 1;12(9):2856-61.
| Cas No. | 174402-32-5 | SDF | |
| 别名 | J 107088; PF 804950 | ||
| Canonical SMILES | O=C1N(NC(CO)CO)C(C2=C1C3=C(C4=C2C5=C(N4[C@H]6[C@@H]([C@H]([C@@H]([C@@H](CO)O6)O)O)O)C=C(O)C=C5)NC7=C3C=CC(O)=C7)=O | ||
| 分子式 | C29H28N4O11 | 分子量 | 608.55 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6433 mL | 8.2163 mL | 16.4325 mL |
| 5 mM | 0.3287 mL | 1.6433 mL | 3.2865 mL |
| 10 mM | 0.1643 mL | 0.8216 mL | 1.6433 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。
A phase I dose-escalation study of Edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors
Anticancer Drugs 2010 Aug;21(7):716-23.PMID:20581657DOI:10.1097/CAD.0b013e32833cb658.
Edotecarin (J-107088), a novel inhibitor of topoisomerase I has an additive effect on colon cell lines (HCT-116) when combined with 5-fluorouracil (5-FU). We conducted a phase I study to determine the maximum tolerated dose and recommended a phase II dose of Edotecarin in combination with infusional 5-FU/leucovorin (LV) in patients with advanced solid tumors. Patients and cohorts of three to six patients were sequentially enrolled at progressively higher dose levels of Edotecarin administered as a 1-h intravenous (IV) infusion every 2 weeks. The Edotecarin starting dose was 6 mg/m, followed by 200 mg/m LV IV infusion administered over 2 h, then 400 mg/m bolus dose of 5-FU before the start of 2400 mg/m 5-FU continuous infusion for a further 46 h. Patients were evaluated for safety, pharmacokinetics, and tumor response according to the Response Evaluation Criteria in Solid Tumors criteria. Fourteen patients (10 male; four female) received a total of 90 cycles (range 3-18). Dose-limiting toxicities were observed in five of the 14 patients treated in the study. All dose-limiting toxicities were related to neutropenia. Only the 6 and 8 mg/m Edotecarin dose levels were explored; however, no maximum tolerated dose was declared. One confirmed complete response in a patient with hepatocellular carcinoma and seven stable disease responses were achieved in the 14 treated patients. Pharmacokinetic analysis showed that Edotecarin achieved and maintained apparent steady-state plasma concentrations during the IV administration in both the cycles. The administration of Edotecarin in combination with infusional 5-FU/LV once every 14 days, even without the 5-FU bolus, did not permit adequate time for recovery from neutropenia.
A phase I study of the safety and pharmacokinetics of Edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors
Cancer Chemother Pharmacol 2007 Jan;59(1):139-47.PMID:16819636DOI:10.1007/s00280-006-0267-9.
Purpose: To assess the maximum tolerated dose, safety, and pharmacokinetic (PK) profile of escalating doses of the novel topoisomerase I (topo I) inhibitor Edotecarin (J-107088) given as a 2-h intravenous (IV) infusion once every 21 days in patients with advanced solid tumors who had not responded to standard therapy. Patients and methods: Twenty-nine patients (18M:11F) received a 2-h IV infusion of Edotecarin in doses of 6, 8, 11, 13, or 15 mg/m(2) every 21 days (with an additional 1-2 weeks permitted for recovery) and were evaluated for safety, PK, and tumor response. Results: The most common non-hematologic toxicities were grade 1-2 nausea, fatigue, anorexia, vomiting, and fever. The most common hematologic toxicities were grade 1-2 thrombocytopenia and grade 3-4 neutropenia, leukopenia, and anemia. No grade 3-4 diarrhea was reported. Dose-limiting toxicities were observed in four patients at the 15 mg/m(2) dose and one patient at the 13 mg/m(2) dose. These toxicities included grade 3 nausea, vomiting, headache, and fatigue, as well as grade 4 neutropenia and febrile neutropenia. The maximum tolerated dose was declared at 15 mg/m(2). One patient with bladder cancer had a confirmed partial response at a dose of 13 mg/m(2). There was a trend to dose-proportional increases in Edotecarin peak plasma concentrations and area under the curve values. Renal excretion of Edotecarin was minimal (3-8% of the dose). Conclusion: The recommended Phase II dose of Edotecarin is 13 mg/m(2) once every 21 days. The toxicities in this study were those typical of cytotoxic chemotherapy and less severe than those associated with other topo I inhibitors. The observed safety profile and preliminary evidence of clinical benefit warrant further investigation of this drug as monotherapy or part of combination therapy in patients with solid tumors.
Edotecarin: a novel topoisomerase I inhibitor
Clin Colorectal Cancer 2005 May;5(1):27-36.PMID:15929804DOI:10.3816/ccc.2005.n.014.
Edotecarin (PHA-782615; formerly J-107088) is a derivative of NB-506, an indolocarbazole antitumor agent. It is a novel inhibitor of topoisomerase I that induces single-strand DNA cleavage more effectively than NB-506 or camptothecin (CPT) and at different DNA sequences. The DNA-topoisomerase I complexes induced by Edotecarin are more stable than those occurring after exposure to CPT or NB-506. The antitumor activity of Edotecarin is less cell cycle dependent than other topoisomerase I inhibitors. Being an indolocarbazole, it is structurally related to staurosporine but does not possess protein kinase inhibitory properties. In addition, Edotecarin does not form active metabolites and is not a substrate for in vitro P450-mediated metabolism. The antitumor activity of Edotecarin has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in breast, cervix, pharynx, lung, prostate, colon, gastric, and hepatic cancer models. Edotecarin is effective on cells that have acquired resistance related to P-glycoprotein. In vitro synergy has been demonstrated when Edotecarin was tested in combination with cisplatin, 5-fluorouracil, etoposide, paclitaxel, doxorubicin, vincristine, CPT, and gemcitabine. Three phase I and 5 phase II studies have been carried out to date. Combination studies of Edotecarin with other chemotherapeutic agents are in current clinical trials. The primary dose-limiting toxicities were grade 3/4 neutropenia and febrile neutropenia. Dose-limiting diarrhea was observed only with a twice-weekly administration schedule. Recent progress in preclinical and clinical studies of Edotecarin is reviewed.
Antitumor efficacy of Edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model
Clin Cancer Res 2006 May 1;12(9):2856-61.PMID:16675581DOI:10.1158/1078-0432.CCR-05-1859.
The novel indolocarbazole Edotecarin (J-107088, formerly ED-749) differs from other topoisomerase I inhibitors both pharmacokinetically and pharmacodynamically. In vitro, it is more potent than camptothecins and has a variable cytotoxic activity in 31 different human cancer cell lines. Edotecarin also possesses greater than additive inhibitory effects on cell proliferation when used in combination with other agents tested in vitro against various cancer cell lines. The present in vivo studies were done to extend the in vitro findings to characterize the antitumor effects of Edotecarin when used either alone or in combination with other agents (i.e., 5-fluorouracil, irinotecan, cisplatin, oxaliplatin, and SU11248) in the HCT-116 human colon cancer xenograft model. Treatment effects were based on the delay in onset of an exponential growth of tumors in drug-treated versus vehicle control-treated groups. In all studies, Edotecarin was active both as a single agent and in combination with other agents. Combination therapy resulted in greater than additive effects, the extent of which depended on the specific dosage regimen. Toxicity in these experiments was minimal. Of all 359 treated mice, the six that died of toxicity were in the high-dose Edotecarin/oxaliplatin group. The results suggest that Edotecarin may serve as effective chemotherapy of colon cancer when used as a single agent, in combination with standard regimens and other topoisomerase inhibitors or with novel agents, such as the multitargeted tyrosine kinase inhibitor SU11248.
Edotecarin
IDrugs 2004 Feb;7(2):173-7.PMID:15057663doi
Banyu Pharmaceutical Co Ltd and Pfizer Inc (formerly Pharmacia Corp) are developing Edotecarin, an indolocarbazole topoisomerase I inhibitor, for the potential treatment of solid tumors.