鹽酸伊立替康三水合物作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetIrinotecan hydrochloride trihydrateCat. No.: HY-16568CAS No.: 136572-09-3分式: CHClNO分量: 677.18作靶點(diǎn): Topoisomerase; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (73.84 mM; Need ultrasonic)

2、H2O : 1.52 mg/mL (2.24 mM; Need ultrasonic and warming)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 1.4767 mL 7.3836 mL 14.7671 mL5 mM 0.2953 mL 1.4767 mL 2.9534 mL10 mM 0.1477 mL 0.7384 mL 1.4767 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-8

3、0C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.69 mM); C

4、lear solution此案可獲得 2.5 mg/mL (3.69 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 儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.69 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL

5、(3.69 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 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.69 mM); Clear solution; Need warming此案可獲得 2.5 mg/mL (3.69 mM) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合

6、均勻。BIOLOGICAL ACTIVITY物活性 Irinotecan hydrochloride trihydrate種拓?fù)洚悩?gòu)酶 I (topoisomerase I) 抑制劑，具有抗腫瘤活性。IC & Target Topoisomerase I體外研究 Irinotecan hydrochloride trihydrate is a topoisomerase I inhibitor. Irinotecan inhibits the growth of LoVo and HT-29cells, with IC50s of 15.8 5.1 and 5.17 1.4 M, respec

7、tively, and induces similar amounts of cleavable complexes inboth in LoVo and HT-29 cells2. 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 growth of tumors by intratumoral i

8、njection daily for 5 days, ontwo consecutive weeks in rats, and such effects also occur via continuous intraperitoneal infusion by osmotic minipump into mice. However, Irinotecan (10 mg/kg) shows no effect on the growth of tumor by i.p1. Irinotecan(CPT-11, 100-300 mg/kg, i.p.) apparently suppresses

9、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%,respectively, and both are more

10、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 with increasing concentrations of

11、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. The IC50 values are then estimated

12、 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 injection at 0.1 cc volume of the app

13、ropriate 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 0.9% sodiumchloride solution by in

14、tratumoral 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)Page 2 of 3 www.MedChemE Genome Med. 2016 Oct 31;8(1):116. Theranostics. 2019 May 31;9(13):3732-3753. PLoS

15、 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.MedChemEREFERENCES1. Morales C, et al. Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tum

16、or. 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 irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced humancolon tumor xenografts in mice. Cancer Chemother Pharmacol. 2004 Mar;53