生物活性

• 描述Tumor suppressor p53 is a powerful growth suppressive and pro-apoptotic protein that plays a central role in protectionfrom tumor development. The overproduction of MDM2, the primary negative regulator of p53, effectively disables p53 function. RG7388, a potent and selective MDM2 antagonist, inhibits p53-MDM2 interaction with an IC₅₀ value of 6 nM. RG7388 induced dose-dependent p53 stabilization, cell cycle arrest, and apoptosis in cancer cells expressing wild-type p53, consistent with a nongenotoxic p53 activation mechanism^[2]. In the MDM2-amplified SJSA1 osteosarcoma cell line, a significant apoptotic response over the control was induced with both the single 300 nmol/L and 1.8 μmol/L concentrations of RG7388 for 16 hours (P < 0.005), with the 1.8 μmol/L concentration providing optimal response. In SJSA osteosarcoma xenograft-bearing mice, the once-daily dose of 30 mg/kg of RG7388 (total 210 mg/kg/wk) seemed to be the most effective dose at inhibiting tumor growth (>100% TGI with 9 partial regressions), the 50 mg/kg of RG7388 given twice a week (total 100 mg/kg/wk) was equivalent by statistical analysis (96% TGI with 3 partial regressions; P > 0.05) ^[1]. It also achieved 88% tumor growth inhibition against established human SJSA1 osterosarcoma xenografts in nude mice at a dose of 12.5 mg/kg^[2].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HCT116 cells	-	Cytotoxic assay	-	Cytotoxicity against human HCT116 cells expressing wild type p53 assessed as growth inhibition by MTT assay, IC50=0.01 μM	23808545
  MDA-MB-435 cells	-	Cytotoxic assay	-	Cytotoxicity against human MDA-MB-435 cells expressing p53 mutant assessed as growth inhibition by MTT assay, IC50=9.1 μM	23808545
  RKO cells	-	Cytotoxic assay	-	Cytotoxicity against human RKO cells expressing wild type p53 assessed as growth inhibition by MTT assay, IC50=0.07 μM	23808545

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• 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
  NCT03158389	Glioblastoma, Adult	Phase 1 Phase 2	Recruiting	September 30, 2024	Germany ... more >> Charité Berlin, Neurosurgery Not yet recruiting Berlin, Germany Knappschaftskrankenhaus Bochum GmbH, Neurology Clinic Not yet recruiting Bochum, Germany University Hospital Bonn, Neurology Clinic Not yet recruiting Bonn, Germany University Hospital Cologne, Neurosurgery Not yet recruiting Cologne, Germany University Hospital Dresden, Neurosurgery Not yet recruiting Dresden, Germany University Hospital Essen, Neurology Clinic Not yet recruiting Essen, Germany University Hospital Frankfurt, Neurooncology Not yet recruiting Frankfurt am Main, Germany University Hospital Heidelberg, Neurology Clinic Recruiting Heidelberg, Germany University Hospital Saarland, Neurosurgery Not yet recruiting Homburg, Germany University Hospital Mainz, Neurosurgery Not yet recruiting Mainz, Germany University Hospital Mannheim, Neurology Clinic Not yet recruiting Mannheim, Germany University Hospital Regensburg, Neurology Clinic Not yet recruiting Regensburg, Germany University Hospital Tuebingen, Neurooncology Not yet recruiting Tübingen, Germany Collapse <<
  NCT03566485	Stage III Breast Cancer ... more >> Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Estrogen Receptor-positive HER2/Neu Negative Collapse <<	Phase 1 Phase 2	Recruiting	July 2024	United States, Tennessee ... more >> Vanderbilt-Ingram Cancer Center Recruiting Nashville, Tennessee, United States, 3720932 Contact: Clinical Trials Information Program    800-811-8480    cip@vanderbilt.edu    Principal Investigator: Ingrid Mayer, MD Collapse <<
  NCT03135262	Follicular Lymphoma ... more >> Lymphoma, Large B-Cell, Diffuse Collapse <<	Phase 1 Phase 2	Recruiting	October 27, 2022	United States, Colorado ... more >> University of Colorado Recruiting Aurora, Colorado, United States, 80045-2517 United States, Illinois The University of Chicago Medical Center Recruiting Chicago, Illinois, United States, 60637 United States, Kentucky Norton Cancer Institute - Dutchmans Recruiting Louisville, Kentucky, United States, 40207 United States, New York Mount Sinai Medical Center Recruiting New York, New York, United States, 10029 United States, Pennsylvania Allegheny General Hospital Not yet recruiting Pittsburgh, Pennsylvania, United States, 15212 Guthrie Clinic Recruiting Sayre, Pennsylvania, United States, 18840 United States, Virginia Virginia Commonwealth University - Massey Cancer Center Withdrawn Richmond, Virginia, United States, 23298 United States, Washington Swedish Cancer Inst. Recruiting Seattle, Washington, United States, 98104 Australia, New South Wales Prince of Wales Hospital Recruiting Randwick, New South Wales, Australia, 2031 Westmead Hospital Recruiting Westmead, New South Wales, Australia, 2145 Australia, Western Australia Linear Clinical Research Limited Recruiting Nedlands, Western Australia, Australia, 6009 Germany Klinikum Augsburg Recruiting Augsburg, Germany, 86156 Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden Recruiting Dresden, Germany, 01307 SLK-Kliniken Heilbronn GmbH Recruiting Heilbronn, Germany, 74078 Klinikum Kassel; Klinik für Onkologie und Hämatologie Recruiting Kassel, Germany, 34125 Universitätsklinikum Köln Recruiting Köln, Germany, 50937 Klinikum rechts der Isar der TU München Recruiting München, Germany, 81675 Universitätsklinikum Würzburg; Studienzentrale Hämatologie/Onkologie Recruiting Würzburg, Germany, 97080 Korea, Republic of Keimyung University Dongsan Medical Center Recruiting Daegu, Korea, Republic of, 41931 National Cancer Center Recruiting Gyeonggi-do, Korea, Republic of, 10408 Severance Hospital Recruiting Seoul, Korea, Republic of, 03722 Asan Medical Center Recruiting Seoul, Korea, Republic of, 05505 Samsung Medical Center Recruiting Seoul, Korea, Republic of, 6351 New Zealand Christchurch Hospital Recruiting Christchurch, New Zealand, 8011 Auckland Clinical Studies Limited Recruiting Grafton, New Zealand, 1010 Collapse <<

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