Toxicological evaluation of an apicidin derivative, histone deacetylase inhibitor SD-2007 in mice.
SD-2007 is a new derivative of apicidin, an anti-parasitic agent and a histone deacetylase (HDAC) inhibitor. A subacute toxicological evaluation of SD-2007 was investigated for 2 weeks in ICR mice. After oral administration of SD-2007 (0, 0.2, 1, 5 or 25 mg/mouse), the clinical signs, mortalities, body weight changes, blood biochemical parameters, absolute and relative organ weights were examined. One day after the administration of SD-2007, excretion of soft feces in 1 and 5 mg/head groups, and one male in 25 mg/mouse group developed diarrhea, but theses complications were disappeared two days after administration. No mortalities were observed in animals up to 25 mg/mouse (LD(50), >25 mg/kg), but absolute and relative weights of testes were significantly lower at the highest dose group (25 mg/mouse) and serum LDH and glucose levels were elevated in male mice. In addition, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were reduced in female mice at all dosages. These data suggest that SD- 2007 may be sex specific and be toxic to the male reproductive organ, and thus our findings require further investigation and in particular chronic toxicological investigations should be investigated.
Kwack
Seung Jun
SJ
Department of Toxicological Research, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, 122-704, Korea.
Kim
Kyu Bong
KB
Lee
Byung Mu
BM
D000284:Administration, Oral; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D056572:Histone Deacetylase Inhibitors; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000633:toxicity*; D012737:Sex Factors; D013997:Time Factors
D000977:Antiparasitic Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C506660:SD-2007