生物活性

• 描述SN-38, a metabolite of CPT-11, is a semisynthesized derivative of camptothecin with much stronger cytotoxicity and single-strand breaks in vitro than CPT-11, which inhibits Topoisomerase I with IC50 values of 0.74μM and 1.9μM for inhibition of Topoisomerase I activity of P388 cells and Ehrlich cells, respectively. SN-38 inhibited topoisomerase I-induced relaxation of supercoiled DNA dose-dependently at concentrations ranging in 0.1-10μM. P388 cells exposure to SN-38 at concentration ranging in 0.01-1μM exhibited dose-dependent inhibition of DNA synthesis (IC50 of 77nM, 2-hour incubation) and RNA synthesis (1.3μM, 3-hour incubation), but no alteration in protein synthesis. Dose-dependent DNA single-strand breaks can also be observed in P388 cells treated with 0.5-2μM for 1h, without obvious double-strand breaks. CPT-11 is converted to SN-38 more efficiently in mice, but shows low efficiency on conversion into SN-38 in patients due to the difference in metabolic pathway.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HEK293 cells	-	Cytotoxic assay	72 h	Intrinsic cytotoxicity against HEK293 cells assessed as reduction in cell viability after 72 hrs by MTT assay	25272055
  human A2780 cells	-	Cytotoxic assay	72 h	Cytotoxicity against human A2780 cells overexpressing alpha5beta3 integrin assessed as cell survival after 72 hrs by SRB assay, IC50=9 nM	22959246
  human A549 cells	-	Cytotoxic assay	3 days	Cytotoxicity against human A549 cells assessed as growth inhibition after 3 days by SRB assay, IC50=2.72 nM	24529870

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• 动物研究
  剂量	Rat: 2 mg/kg[3] (i.v.); 40 mg/kg (p.o.) Mice: 5 mg/kg- 75 mg/kg[4] (i.v.)
  给药途径	i.v., p.o.
  动物药代数据	Animal Mice[4] Dose 5 mg/kg Administration i.v. p.o. Cmax 647 ng/ml (i.v.) 30 ng/ml (p.o.) AUC0→∞ 279 ng·h/ml (i.v.) 86 ng·h/ml (p.o.) Tmax 1 h (p.o.)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01605344	Advanced Adenocarcinoma of the... more >> Colon or Rectum Collapse <<	Phase 1	Withdrawn(Study was withdrawn ... more >>due to lack of patient enrollment.) Collapse <<	July 2014	United States, North Carolina ... more >> University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina, United States, 27599 Collapse <<
  NCT01051765	Advanced Esophageal Squamous C... more >>arcinoma Collapse <<	Phase 2	Unknown	August 2012	China, Beijing ... more >> Zhang Xiaodong Recruiting Beijing, Beijing, China, 100142 Contact: zhang xiaodong, MD    86-10-88196175    zxd0829@yahoo.com.cn Collapse <<
  NCT01925274	Metastatic Colorectal Cancer	Phase 2	Terminated(Enrollment to the s... more >>tudy was terminated on 11Nvo2014 due to slow recruitment. There were no safety or efficacy issues that contributed to this decision.) Collapse <<	-	United States, California ... more >> CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center Bakersfield, California, United States, 93309 Drug Management Only: UCLA West Medical Pharmacy, Att: Steven L Wong, Pharm D Los Angeles, California, United States, 90095-7349 Drug Management Only: UCLA West Medical Pharmacy Los Angeles, California, United States, 90095-7349 UCLA West Medical Pharmacy Los Angeles, California, United States, 90095-7349 Regulatory Management Only: TRIO-US Central Administration Los Angeles, California, United States, 90095 TRIO-US Central Administration (Regulatory Management only) Los Angeles, California, United States, 90095 TRIO_US Los Angeles, California, United States, 90095 West Valley Hematology/Oncology Med Group Northridge, California, United States, 91328 United States, Missouri Siteman Cancer Center - West County Creve Coeur, Missouri, United States, 63141 Barnes-Jewish Hospital Saint Louis, Missouri, United States, 63110 Drug Shipping Address: Washington University Infusion Center Pharmacy Saint Louis, Missouri, United States, 63110 Washington University School of Medicine Saint Louis, Missouri, United States, 63110 Siteman Cancer Center - South County Saint Louis, Missouri, United States, 63129 Siteman Cancer Center - St Peters Saint Peters, Missouri, United States, 63376 United States, Nevada Regulatory Office: Comprehensive Cancer Centers of Nevada Henderson, Nevada, United States, 89014 Comprehensive Cancer Centers of Nevada Henderson, Nevada, United States, 89052 Comprehensive Cancer Centers of Nevada Henderson, Nevada, United States, 89074 Comprehensive Cancer Centers of Nevada Las Vegas, Nevada, United States, 89128 Comprehensive Cancer Centers of Nevada Las Vegas, Nevada, United States, 89148 Comprehensive Cancer Centers of Nevada Las Vegas, Nevada, United States, 89169 United States, New York Roswell Park Cancer Institute Buffalo, New York, United States, 14263 United States, Washington Kadlec Clinic Hematology and Oncology Kennewick, Washington, United States, 99336 Kadlec Medical Center Richland, Washington, United States, 99352 Outpatient Imaging Center Richland, Washington, United States, 99352 Spokane Valley Cancer Center Spokane Valley, Washington, United States, 99216 Medical Oncology Associates, PS Spokane, Washington, United States, 99208 Japan Aichi cancer center central hospital Nagoya, Aichi, Japan, 464-8681 National Cancer Center Hospital East Kashiwa, Chiba, Japan, 277-8577 Korea, Republic of National Cancer Center Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769 Seoul National University Hospital / Department of Internal Medicine Seoul, Korea, Republic of, 110-744 Samsung Medical Center Seoul, Korea, Republic of, 135-710 Asan Medical Center Seoul, Korea, Republic of, 138-736 Spain Hospital General Universitario Gregorio Marañón Madrid, Spain, 28009 Collapse <<

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