"目录号: HY-13767
Tirapazamine(SR259075; Win59075; SR4233)可在低氧水平下被活化为毒性自由基，是一种实验性抗癌化合物。
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生物活性
Description
Tirapazamine(SR259075; Win59075; SR4233) is an experimental anticancer drug that is activated to a toxic radical only at very low levels of oxygen; a phenomenon known as tumor hypoxia.IC50 value:Target: in vitro: Tirapazamine could downregulate HIF-1α expression by decreasing HIF-1α protein synthesis. The enhanced apoptosis induced by tirapazamine plus SN-38 (the active metabolite of irinotecan) was accompanied by increased mitochondrial depolarization and caspase pathway activation [1].in vivo: The combination treatment dramatically inhibited the accumulation of HIF-1α protein, decreased the HIF-1α transcriptional activation, and impaired the phosphorylation of proteins involved in the homologous recombination repair pathway, ultimately resulting in the synergism of these two drugs. Moreover, the increased anticancer efficacy of tirapazamine combined with irinotecan was further validated in a human liver cancer Bel-7402 xenograft mouse model [1]. Rats were intraperitoneally injected six times once a week with tirapazamine in two doses, 5 (5TP) and 10 mg/kg (10TP), while doxorubicin was administered in dose 1.8 mg/kg (DOX). Subsequent two groups received both drugs simultaneously (5TP+DOX and 10TP+DOX). Tirapazamine reduced heart lipid peroxidation and normalised RyR2 protein level altered by doxorubicin [2].
Clinical Trial
Sanofi
Head and Neck Neoplasms
October 2002
Phase 3
Teclison Ltd.
Hepatocellular Carcinoma
September 2014
Phase 1
Southwest Oncology Group-National Cancer Institute (NCI)
Cervical Cancer
August 1998
Phase 2
National Cancer Institute (NCI)-NCIC Clinical Trials Group
Cervical Adenocarcinoma-Cervical Adenosquamous Cell Carcinoma-Cervical Squamous Cell Carcinoma-Stage IB Cervical Cancer-Stage IIA Cervical Cancer-Stage IIB Cervical Cancer-Stage III Cervical Cancer-Stage IVA Cervical Cancer
February 2006
Phase 3
Sanofi-Groupe Oncologie Radiotherapie Tete et Cou
Head and Neck Squamous Cell Carcinoma
April 2005
Phase 3
National Cancer Institute (NCI)
Limited Stage Small Cell Lung Cancer
September 2003
Phase 2
Peter MacCallum Cancer Centre, Australia-National Cancer Institute (NCI)
Cervical Cancer
December 2004
Phase 1
Teclison Ltd.
Carcinoma, Hepatocellular
October 1, 2017
Phase 2
Gynecologic Oncology Group-National Cancer Institute (NCI)
Ovarian Cancer-Primary Peritoneal Cavity Cancer
June 2001
Phase 2
National Cancer Institute (NCI)
Unspecified Childhood Solid Tumor, Protocol Specific
August 1998
Phase 1
Stanford University-National Cancer Institute (NCI)
Squamous Neck Carcinoma of the Head and Neck Cancer (SCCHN)
June 1996
Phase 2
Sanofi-National Cancer Institute (NCI)
Lung Cancer
July 2000
Phase 3
City of Hope Medical Center-National Cancer Institute (NCI)
Unspecified Adult Solid Tumor, Protocol Specific
March 2000
Phase 1
California Cancer Consortium-National Cancer Institute (NCI)
Lung Cancer
March 2002
Phase 1
Southwest Oncology Group-National Cancer Institute (NCI)
Lung Cancer
November 2000
Phase 3
Southwest Oncology Group-National Cancer Institute (NCI)
Lung Cancer
October 2000
Phase 1
National Cancer Institute (NCI)
Alveolar Childhood Rhabdomyosarcoma-Embryonal Childhood Rhabdomyosarcoma-Embryonal-botryoid Childhood Rhabdomyosarcoma-Previously Treated Childhood Rhabdomyosarcoma-Recurrent Childhood Rhabdomyosarcoma
November 2001
Phase 2
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