生物活性

• 描述Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states^[1]. EDO-S101, a pan HDAC inhibitor, inhibits HDAC6, HDAC1, HDAC2 and HDAC3 with IC₅₀ values of 6 nM, 9 nM, 9 nM and 25 nM, respectively. EDO-S101 (10 mg/kg i.v.; 1 h) inhibited HDAC activity in rat PBMCs in a cellular assay by approximately 90%. in HL60 and MM1S Cells, EDO-S101 demonstrated significant acetylation of lysine residues, further confirming the HDAC-inhibition function of the vorinostat moiety in the EDO-S101 molecule. Alkylation was evaluated in vitro in myeloid (HL60 AML cell line) and lymphoid cell lines. EDO-S101 caused DNA cross links in the Comet assay at low concentrations demonstrating the alkylating function of the molecule. Exposure to EDO-S101 in vivo caused a strong DNA repair response evidenced by activation of pH2AX and p53 in tumors taken from mice bearing subcutaneous human Burkitt's lymphoma. Moreover, 4 μM EDO-S101 triggered apoptosis in vitro and in vivo, resulting in strong antitumor activity in HL60 and Daudi cells and in the Daudi xenograft model^[2].
• 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
  NCT03687125	Multiple Myeloma in Relapse ... more >> Multiple Myeloma Progression Multiple Myeloma With Failed Remission Collapse <<	Phase 1 Phase 2	Recruiting	March 7, 2023	United States, Alabama ... more >> University of Alabama Recruiting Birmingham, Alabama, United States, 35294 Contact: Luciano Costa, MD          United States, Kansas University of Kansas Medical Center Kansas City Not yet recruiting Kansas City, Kansas, United States, 66160 Contact: Leyla Shune, MD          United States, New York Memorial Sloan Kettering Cancer Centre Not yet recruiting New York, New York, United States, 10065 Contact: Sergio Giralt, MD          United States, North Carolina Carolinas Healthcare System Not yet recruiting Charlotte, North Carolina, United States, 28204 Contact: Shebli Atrash          United States, Tennessee Vanderbilt-Ingram Cancer Center Not yet recruiting Nashville, Tennessee, United States, 37203 Contact: Michael Byrne, MD          United States, Texas University of Texas MD Anderson Cancer Center Not yet recruiting Houston, Texas, United States, 77030 Contact: Qaiser Bashir, MD          United States, Wisconsin Froedtert & Medical College of Wisconsin, Cancer Center - Froedtert Hospital Not yet recruiting Milwaukee, Wisconsin, United States, 53226 Contact: Anita D'Souza          Norway Oslo Myeloma Center, Oslo University Hospital Not yet recruiting Oslo, Norway Contact: Fredrik Hellem Schjesvold          Switzerland Universitatsspital Basel Not yet recruiting Basel, Switzerland Contact: Dominik Heim          Universitatsspital Bern Not yet recruiting Bern, Switzerland Contact: Thomas Pabst          Department of Clinical Research Oncology/Hematology, Kantonsspital St. Gallen Not yet recruiting Saint Gallen, Switzerland Contact: Dagmar Hess-Mildenberger          University Hospital Zurich Not yet recruiting Zürich, Switzerland Contact: Rouven Muller Collapse <<
  NCT03452930	Malignant Neoplasms of Eye Bra... more >>in and Other Parts of Central Nervous System Unmethylated Glioblastoma Collapse <<	Phase 1	Recruiting	October 2020	United States, Texas ... more >> University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact       sweathers@mdanderson.org Collapse <<
  NCT02576496	Hematological Malignancies ... more >> Multiple Myeloma Hodgkin's Lymphoma Peripheral T-cell Lymphoma Non-Hodgkin's Lymphoma Collapse <<	Phase 1	Recruiting	May 2019	United States, Arizona ... more >> Mayo Clinic Recruiting Phoenix, Arizona, United States, 85054 Contact: Leif Bergsagel, MD    480-301-8335    bergsagel.leif@mayo.edu    Principal Investigator: Leif Bergsagel, MD          United States, Florida Mayo Clinic Cancer Center Recruiting Jacksonville, Florida, United States, 32224 Contact: Han W Tun, MD    904-953-7290    tun.han@mayo.edu    Contact: Kathleen M Burke, RN    904 953 6174    burke.kathleen@mayo.edu    Principal Investigator: Han W. Tun, MD          United States, New York Columbia University Medical Center Recruiting New York, New York, United States, 10019 Contact: Owen A O'Connor, MD,PhD    212-326-5720    oo2130@cumc.columbia.edu    Contact: Michelle A Malanga, MPA    212-326-5731    mm4629@cumc.columbia.edu    Germany University Hospital of Heidelberg - medical department V Not yet recruiting Heidelberg, Germany, 69120 Principal Investigator: Hartmut Goldschmidt, MD          University Hospital of Cologne - Department I of Internal Medicine Not yet recruiting Köln, Germany, 50937 Principal Investigator: Von Treskow, MD          Italy Institute of Hematology "L. A. Seràgnoli", University of Bologna Recruiting Bologna, Italy, 40138 Contact: Luigi Zinzani, MD    +39 0512143680    pierluigi.zinzani@unibo.it    Principal Investigator: Luigi Zinzani, MD          National Cancer Institute, Fondazione 'G. Pascale' Recruiting Naples, Italy, I-80131 Contact: Antonio Pinto, MD    +39 081 5903 382    apinto.int.napoli@tin.it    Principal Investigator: Antonio Pinto, MD          Switzerland Kantonsspital St.Gallen Recruiting St.Gallen, Switzerland, 9007 Contact: Christoph Driessen, MD    41 71 494 11 62    christoph.driessen@kssg.ch    Principal Investigator: Christoph Driessen, MD Collapse <<

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