Belotecan hydrochloride (CKD-602)
(Synonyms: CKD-602盐酸盐,CKD-602) 目录号 : GC33066
A DNA topoisomerase I inhibitor
Cas No.:213819-48-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
The cells are treated with different concentrations (0.01, 0.1, 0.5, 1, 5 and 10 μg/mL) of belotecan for 24, 48 and 72 h. Control samples of each cell line are treated with medium only. Cell viability is measured using the MTS assay[1]. |
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Animal experiment: |
Mice: Nude mice with established U87MG glioma are treated with a dose of belotecan of 0 mg/kg (control group, injection with saline), 40 mg/kg (group A) or 60 mg/kg (group B). Thereafter, the dose is repeated once every 4 days for a total of four doses. Tumor volume is measured histologically and apoptosis is detected[1]. |
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References: [1]. Kim YK, et al. Anticancer effects of CKD-602 (Camtobell®) via G2/M phase arrest in oral squamous cell carcinoma cell lines. Oncol Lett. 2015 Jan;9(1):136-142. |
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Belotecan is an inhibitor of DNA topoisomerase I (IC50 = 0.119 ?g/ml) and a derivative of the DNA topoisomerase I inhibitor camptothecin .1 It inhibits the proliferation of various cancer cell lines, including KATO III stomach, HT-29 colon, A549 lung, MDA-MB-231 breast, and SKOV3 ovarian cancer cells (IC50s = 160, 10.9, 9, 345, and 31 ng/ml, respectively). Belotecan (150 ng/ml) induces apoptosis and cell cycle arrest at the G2/M phase in, and inhibits invasion of, SiHa cervical cancer cells.2 It reduces tumor growth in a Ca Ski cervical cancer mouse xenograft model when administered at a dose of 25 mg/kg. Belotecan (80 ?g/kg) reduces food intake and body weight in pregnant dams and increases fetal deaths and decreases litter size.3 Formulations containing belotecan have been used in the treatment of ovarian and small cell lung cancer.
1.Lee, J.H., Lee, J.M., Kim, J.K., et al.Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitorArch. Pharm. Res.21(5)581-590(1998) 2.Lee, S., Ho, J.Y., Liu, J.J., et al.CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancerMol. Med.25(1)23(2019) 3.Chung, M.-K., Kim, J.-C., and Han, S.-S.Embryotoxic effects of CKD-602, a new camptothecin anticancer agent, in ratsReprod. Toxicol.20(1)165-173(2005)
| Cas No. | 213819-48-8 | SDF | |
| 别名 | CKD-602盐酸盐,CKD-602 | ||
| Canonical SMILES | O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CCNC(C)C)C5=CC=CC=C5N=C4C3=C2)=O.[H]Cl | ||
| 分子式 | C25H28ClN3O4 | 分子量 | 469.96 |
| 溶解度 | DMSO : ≥ 50 mg/mL (106.39 mM) | 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。 |
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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 | 2.1278 mL | 10.6392 mL | 21.2784 mL |
| 5 mM | 0.4256 mL | 2.1278 mL | 4.2557 mL |
| 10 mM | 0.2128 mL | 1.0639 mL | 2.1278 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。
The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer
J Chemother 2010 Jun;22(3):197-200.PMID:20566426DOI:10.1179/joc.2010.22.3.197.
This study evaluated the efficacy and toxicity of belotecan (CKD-602), a new camptothecin analogue topoisomerase i inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. Data from 63 patients who had been treated with intravenous belotecan (0.5 mg/m(2)/day), administered for 5 days every 3 weeks at a single institute in Seoul, Korea, were collected retrospectively. The overall response rate was 30.2% including 9 patients with complete remission (CR) and the progression free survival was a median of 6.5 (0.7 - 29.7) months. The platinumsensitive group had a significantly higher response rate and longer progression-free survival more than the platinum-resistant group. The most common adverse effect of belotecan was hematologic toxicity which was tolerable. As a single chemotherapy agent, belotecan was effective in treating recurrent or refractory epithelial ovarian cancer, and had acceptable toxicity. Further studies of the efficacy of belotecan in combination with platinum or the other agents are warranted.
CKD-602. Chong Kun Dang
Curr Opin Investig Drugs 2003 Dec;4(12):1455-9.PMID:14763132doi
Chong Kun Dang is developing the camptothecin analog CKD-602 for the potential treatment of cancer. By August 2000, phase II trials of CKD-602 were underway.
CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer
Mol Med 2019 May 28;25(1):23.PMID:31138113DOI:10.1186/s10020-019-0089-y.
Background: Cervical cancer is the third most common gynecological malignancy. Conventional treatment options are known to be ineffective for the majority of patients with advanced or recurrent cervical cancer. Therefore, novel therapeutic agents for cervical cancer are necessary. In this study, the effects of CKD-602 in cervical cancer were investigated. Methods: Three established human, immortalized, cervical cancer cell lines (CaSki, HeLa and SiHa) were used in this study. Following treatment with CKD-602, apoptosis was quantified using fluorescein isothiocyanate Annexin V-FITC and propidium iodide (PI) detection kit and cell cycle analysis was analyzed using fluorescence activated cell sorting (FACS). Transwell chambers were used for invasion assays. Western blot assay was performed to analyze proteomics. CaSki cells were subcutaneously injected into BALB/c-nude mice and cervical cancer xenograft model was established to elucidate the antitumor effect of CKD-602 in vivo. Results: Treatment with CKD-602 induced apoptosis and increased expression of the enzyme PARP, cleaved PARP, and BAX. In addition, expression of phosphorylated p53 increased. Cell cycle arrest at G2/M phase and inhibition of invasion were detected after treatment with CKD-602. A significant decrease in cervical cancer tumor volume was observed in this in vivo model, following treatment with CKD-602. Conclusions: This is the first report of CKD-602 having an antitumor effect in cervical cancer in both an in vitro and in vivo models. The results of this study indicate that CKD-602 may be a novel potential drug, targeting cervical cancer, providing new opportunities in the development of new therapeutic strategies.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2009 Jun;31(5):341-56.PMID:19649342doi
(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan.
Plasma, tumor, and tissue disposition of STEALTH liposomal CKD-602 (S-CKD602) and nonliposomal CKD-602 in mice bearing A375 human melanoma xenografts
Clin Cancer Res 2007 Dec 1;13(23):7217-23.PMID:18056203DOI:10.1158/1078-0432.CCR-07-1035.
Purpose: S-CKD602 is a STEALTH liposomal formulation of CKD-602, a camptothecin analogue. The cytotoxicity of camptothecin analogues is related to the duration of exposure in the tumor. STEALTH liposomal formulations contain lipid conjugated to methoxypolyethylene glycol and have been designed to prolong drug circulation time, increase tumor delivery, and improve the therapeutic index. For STEALTH liposomal formulations of anticancer agents to achieve antitumor effects, the active drug must be released into the tumor extracellular fluid (ECF). Experimental design: S-CKD602 at 1 mg/kg or nonliposomal CKD-602 at 30 mg/kg was administered once via tail vein to mice bearing A375 human melanoma xenografts. Mice (n = 3 per time point) were euthanized at 0.083 to 24 h, 48 h, and 72 h after S-CKD02 and from 0.083 to 24 h after nonliposomal CKD-602. Plasma samples were processed to measure encapsulated, released, and sum total (encapsulated plus released) CKD-602, and tumor and tissue samples were processed to measure sum total CKD-602. Microdialysis samples of tumor ECF were obtained from 0 to 2 h, 4 to 7 h, and 20 to 24 h after nonliposomal CKD-602 and from 0 to 2 h, 24 to 27 h, 48 to 51 h, and 72 to 75 h after S-CKD602. A liquid chromatography-mass spectrometry assay was used to measure the total (sum of lactone and hydroxyl acid) CKD-602. The area under the concentration-versus-time curves (AUC) from 0 to infinity and time >1 ng/mL in tumor were estimated. Results: For S-CKD602, the CKD-602 sum total AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 201,929, 13,194, and 187 ng/mL h, respectively. For S-CKD602, 82% of CKD-602 remains encapsulated in plasma. For nonliposomal CKD-602, the CKD-602 AUC in plasma and tumor and the CKD-602 AUC in tumor ECF were 9,117, 11,661, and 639 ng/mL.h, respectively. The duration of time the CKD-602 concentration was >1 ng/mL in tumor ECF after S-CKD602 and nonliposomal CKD-602 was >72 and approximately 20 h, respectively. For S-CKD602, the CKD-602 sum total exposure was 1.3-fold higher in fat as compared with muscle. The ratio of CKD-602 sum total exposure in fat to muscle was 3.8-fold higher after administration of S-CKD602 compared with nonliposomal CKD-602. Conclusion: S-CKD602 provides pharmacokinetic advantages in plasma, tumor, and tumor ECF compared with nonliposomal CKD-602 at 1/30th of the dose, which is consistent with the improved antitumor efficacy of S-CKD602 in preclinical studies. The distribution of S-CKD602 is greater in fat compared with muscle whereas the distribution of nonliposomal CKD-602 is greater in muscle compared with fat. These results suggest that the body composition of a patient may affect the disposition of S-CKD602 and released CKD-602.