伊立替康作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetIrinotecanCat. No.: HY-16562CAS No.: 97682-44-5分式: CHNO分量: 586.68作靶點(diǎn): Topoisomerase; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 30 mg/mL (51.14 mM; Need ultrasonic)Solven

2、tMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.7045 mL 8.5225 mL 17.0451 mL5 mM 0.3409 mL 1.7045 mL 3.4090 mL10 mM 0.1705 mL 0.8523 mL 1.7045 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light)。-80C 儲存時，請?jiān)?6 個內(nèi)使，-20C 儲存時，請?jiān)?1 個內(nèi)使。體內(nèi)實(shí)驗(yàn) 請

3、根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.26 mM); Clear solution此案可獲得 2.5 mg/mL (4.26 mM

4、，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.26 mM); Clear solution此案可獲得 2.5 mg/mL (4.26 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO

5、儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。Page 1 of 2 www.MedChemEBIOLOGICAL ACTIVITY物活性 Irinotecan拓?fù)洚悩?gòu)酶 I (topoisomerase I) 抑制劑，通過與拓?fù)洚悩?gòu)酶 I-DNA 復(fù)合物結(jié)合來防 DNA 鏈的再連接。IC & Target Topoisomerase I體外研究 Irinotecan is a topoisomerase I inhibitor. Irinotecan inhibits the growth of LoVo and HT-29 cells, with IC50s of

6、 15.8 5.1 and 5.17 1.4 M, respectively, and induces similar amounts of cleavable complexes in both in LoVo and HT-29cells2. Irinotecan suppresses the proliferation of human umbilical vein endothelial cells (HUVEC), with an IC50 of 1.3 M3.體內(nèi)研究 Irinotecan (CPT-11, 5 mg/kg) significantly inhibits the g

7、rowth of tumors by intratumoral injection daily for 5 days, ontwo consecutive weeks in rats, and such effects also occur via continuous intraperitoneal infusion by osmoticminipump into mice. However, Irinotecan (10 mg/kg) shows no effect on the growth of tumor by i.p1. Irinotecan(CPT-11, 100-300 mg/

8、kg, i.p.) apparently suppresses tumor growth of HT-29 xenografts in athymic female mice byday 21. The two groups of Irinotecan (125 mg/kg) plus TSP-1 (10 mg/kg per day) or Irinotecan (150 mg/kg) incombination TSP-1 (20 mg/kg per day) are nearly equally effective and inhibit tumor growth 84% and 89%,

9、respectively, and both are more effective than Irinotecan alone at doses of 250 and 300 mg/kg3.PROTOCOLCell Assay 2 Exponentially growing cells are seeded in 20 cm2 dishes with an optimal cell number for each cell line (20,000 forLoVo cells, 100,000 for HT-29 cells). They are treated 2 days later wi

10、th increasing concentrations of irinotecan orSN-38 for one cell doubling time (24 h for LoVo cells, 40 h for HT-29 cells). After washing with 0.15 M NaCl, the cellsare further grown for two doubling times in normal medium, detached from the support with trypsin-EDTA andcounted in a hemocytometer. Th

11、e IC50 values are then estimated as the drug concentrations responsible for 50%growth inhibition as compared with cells incubated without drug2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Irinotecan has been administered by intratumoral injec

12、tion at 0.1 cc volume of the appropriate solution, for a dosesAdministration 1 of 5 mg/kg daily for 5 days, on two consecutive weeks, followed by a 7-days rest period, referred to as one cycle oftherapy. Rats receive three cycles over a period of 8 weeks. Control animals receive 0.1 cc of sterile 0.

13、9% sodiumchloride solution by intratumoral injection in the same rule of administration as that of animals of group II1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Genome Med. 2016 Oct 31;8(1):116. Theranostics. 2019 May 31;9(13):3732-37

14、53. PLoS Pathog. 2020 Mar. Cell Death Dis. 2019 Nov 25;10(12):887. J Mol Med (Berl). 2019 Aug;97(8):1183-1193.See more customer validations on HYPERLINK www.MedChemE www.MedChemEPage 2 of 3 www.MedChemEREFERENCES1. Morales C, et al. Antitumoral effect of irinotecan (CPT-11) on an experimental model

15、of malignant neuroectodermal tumor. J Neurooncol. 2002Feb;56(3):219-26.2. Pavillard V, et al. Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines. Cancer Chemother Pharmacol. 2002Apr;49(4):329-35. Epub 2002 Jan 30.3. Allegrini G, et al. Thrombospondin-1 plus irino

16、tecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced humancolon tumor xenografts in mice. Cancer Chemother Pharmacol. 2004 Mar;53(3):261-6. Epub 2003 Dec 5.4. Dela Cruz FS, et al. A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in apediatric poorly differentiated carcinoma. Genome Med. 2016 Oct 31;8(1):116.5. Huang MY, et al. Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis. A