title: The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.
abstract: OBJECTIVE
  UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice.
  
  
  METHODS
  BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored.
  
  
  RESULTS
  UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin.
  
  
  CONCLUSIONS
  In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.
authors.affiliation: 21st Century Therapeutic, Inc., 1366 Hilton Rd., Ferndale, MI 48220, USA. jiajiushaw@gmail.com
authors.forename: Jiajiu
authors.initials: J
authors.lastname: Shaw
authors.forename: Joseph
authors.initials: J
authors.lastname: Media
authors.forename: Ben
authors.initials: B
authors.lastname: Chen
authors.forename: Fredrick
authors.initials: F
authors.lastname: Valeriote
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000494:pharmacology*; D020714:Maximum Tolerated Dose; D051379:Mice; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; C559524:UTL-5g compound; D002945:Cisplatin