生物活性

• 描述Tenofovir is an antiviral agent that selectively inhibits HIV reverse transcriptase (RNA-dependent DNA polymerase) and blocks hepatitis B virus infections as well as prevents cytotoxicity in SIV-infected C-8166 cells in vitro with IC50 value of 1.5 μM. In vitro, a K65R reverse transcriptase mutation in HIV-1 has been selected by tenofovir resulting in 3 to 4-fold reduced susceptibility to tenofovir, HIV expressing the lamivudine-associated M184V RT mutation has shown increased susceptibility to tenofovir, suggesting the better susceptibility of clinical HIV samples. The antiviral activity was determined in the tetracycline-responsive HepAD38 and HepAD79 cells, which are stably transfected with either a cDNA copy of the wild-type pregenomic RNA or with cDNA containing the M550V mutation. As expected, tenofovir proved almost better effective against both viruses. In HepG2 2.2.15 cells， which are routinely used for anti-HBV drug-screening purposes， and HepAD38 cells as comparative, HepAD38 cells produce much larger quantities of HBV than HepG2 2.2.15 cells, and thus allow drug screening in a multiwell plate format, Tenofovir could inhibit HBV replication in HepAD38 cells, which produced much larger quantities of HBV than HepG2 2.2.15 cells, equally with HepG2 2.2.15 cells. In the prevention of SIV infection in adult macaques, tenofovir at a dose of 30 mg/kg, administered once daily beginning either 2 days before or 4 or 24 h after virus inoculation and continued for 4 weeks, completely prevented SIV infection in all macaques without toxicity, whereas all control animals became infected. While in macaques with an established SIV infection, tenofovir caused a 99% reduction of SIV levels in plasma without side effects. For HIV-2 infected pig-tailed macaques, tenofovir was administered subcutaneously at 30 mg/kg starting at 12, 36, or 72 h after viral inoculation: early intervention (at either 12 or 36 h) completely abrogated HIV infection via intravaginal exposure. In human C8166 and H9 cells, antiviral activity of tenofovir against 100 TCID50 wild-type Human immunodeficiency virus and HIV1 were assessed with EC50 values of 7.1 μM and 0.04 μM, respectively.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  C3H/3T3 cells	-	Function assay	6 days	Inhibition of murine sarcoma virus-induced transformation of mouse embryo fibroblast C3H/3T3 cells after 6 days, EC50=0.23 μM	18556209
  C8166 cells	-	Function assay	4 days	Antiviral activity against 100 TCID50 wild-type Human immunodeficiency virus type 2 ROD infected in C8166 cells assessed as inhibition of syncytia formation after 4 days by microscopic analysis, EC50=7.1 μM	21803462
  CEM (human leukemia) cells	-	Function assay	-	Antiviral activity against HIV-1 (IIIB) in CEM (human leukemia) cells, EC50=1.2 μM	14584956

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• 动物研究
  剂量	Mice: 20 mg/kg - 300 mg/kg[3] (i.p.), 50 mg/kg - 1000 mg/kg[4] (p.o.) Woodchucks: 0.5 mg/kg - 5 mg/kg (p.o.)
  给药途径	i.p., 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
  NCT01488526	Hepatitis B Infection ... more >> Chronic Infection Viremia Collapse <<	Phase 4	Active, not recruiting	October 28, 2017	China, Chongqing ... more >> Southwest Hospital Chongqing, Chongqing, China, 400038 China, Hebei The Fifth Hospital of Shijiazhuang Shijiazhuang, Hebei, China, 050021 China, Henan Nanyang Central Hospital Nanyang, Henan, China, 473000 China, Jiangsu The Second Affiliated Hospital of the Southeast University Nanjing, Jiangsu, China, 210003 China, Jilin Hepatobiliary Disease Hospital of Jilin Province Chang Chun, Jilin, China, 130062 Collapse <<
  NCT03270969	HIV Prevention	Phase 1	Active, not recruiting	December 2018	United States, Nebraska ... more >> Specialty Care Center Omaha, Nebraska, United States, 68106 Collapse <<
  NCT00528957	HIV Infections	Phase 3	Completed	-	United States, California ... more >> Jeffrey Goodman Special Care Clinic Los Angeles, California, United States, 90027 University California Los Angeles, School of Medicine, Pediatric, Infectious Diseases Los Angeles, California, United States, 90095 United States, Florida Children's Diagnostic and Treatment Center, Inc Fort Lauderdale, Florida, United States, 33316 University of Florida, Jacksonville Jacksonville, Florida, United States, 32209 United States, Pennsylvania St. Christopher's Hospital for Children Philadelphia, Pennsylvania, United States, 19134 United States, Tennessee St. Jude Children's Research Hospital Memphis, Tennessee, United States, 38105 Panama Hospital del Nino Panama City, Panama United Kingdom Great Ormond Street Hospital London, United Kingdom Imperial College London, Paediatrics Infectious Diseases London, United Kingdom Collapse <<

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