Sodium hydrogen-S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913): toxicity and bone marrow radioprotection.
Experiments have been carried out to compare the toxicity and radioprotective effect of sodium hydrogen-S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913) with those of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721). The drugs were given intraperitoneally to 12 week-old female BALB/c mice 30 minutes before whole body irradiation. Lethality at 30 days was the endpoint used. The drug LD50/30 was 678 mg/kg for WR-2721 and 3574 mg/kg for WR-77913. The LD50/30 for WR-77913 combined with 500 mg/kg of WR-2721 was 3328 mg/kg. The LD50/30 for misonidazole was 380 mg/kg when given in combination with 500 mg/kg of WR-2721 and 801 mg/kg when combined with 2200 mg/kg of WR-77913. Protection of bone marrow by WR-77913 and WR-2721 was comparable at doses close to the maximum tolerable dose (MTD, drug dose lethal to 10% of the animals at 30 days), but WR-77913 gave better protection at 35% of the MTD. These characteristics of low toxicity, non-additive toxicity with WR-2721, less toxicity in combination with misonidazole and adequate bone marrow protection at 25% of the MTD, make WR-77913 a protector worthy of further investigation.
D004999:Amifostine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D005260:Female; D005720:Gamma Rays; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008920:Misonidazole / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000633:toxicity*
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C035284:WR 77913; D008920:Misonidazole; D004999:Amifostine