In Vivo Screening of Radioprotectors.
Annual summary rept. Aug 81-Mar 82,
LITTLE (ARTHUR D) INC CAMBRIDGE MA
Pagination or Media Count:
This report describes results of In Vivo screening of potential radiation protectant agents as part of the USAMRDC antiradiation drug development program. These agents included the known protectors WR 3689 and WR 168643, seven structural analogs of WR 168643, and twelve diverse compounds synthesized by contractors to the USAMRDC. Both WR 3689 and WR 168643 protected mice from bone marrow lethiality when administered intraperitoneally or orally. Oral administration of WR 3689 was maximally effective when given 45 minutes prior to irradiation. Oral WR 168643 produced greatest protection 5 to 15 minutes prior to radiation. Four of seven analogs of WR 168463 exhibited insufficient activity to warrant further study. The remaining three analogs may warrant additional characterization. Among the 12 recently synthesized chemical compounds, only 5 produced greater than 50 survivors when administered intraperitioneally to mice 15 to 30 minutes before irrdiation with a dose previously determined to result in 100 mortality in unprotected mice. One of these agents, WR 249708, which is an analog of WR2721, produced 100 survival at 2 of 3 dose levels tested. This compound will be more fully characterized to determine its oral effectiveness and to compare its protectant properties with that of the parent compound.