1-Isobutanoil-2-isopropylisothiourea Phosphate, T1082: A Safe and Effective Prevention of Radiotherapy Complications in Oncology

The radioprotective effects of a new 1-isobutanoil-2-isopropylisothiourea derivative named T1082 are presented. Research methods included toxic characteristics, radioprotective activity (Till– McCulloch’s test and 30-day survival test) in γ-ray total-body-irradiated mice, and a clinical and histological study of the effect of T1082 on acute radiation skin reactions (RSR) in rats after a single or fractionated β-ray local irradiation. T1082 is more effective than its analogue, the NOS inhibitor T1023, at low concentrations and doses (1/12–1/8 LD10 ), both parenterally and intragastrically. In this case, its therapeutic index (LD50 /ED50 ) reaches 30, and the optimal radioprotective doses (ED84–98 —141–224 mg/kg) are an order less than the maximum tolerated doses—1/16–1/10 LD10 . These properties allowed T1082, at a low intragastrical dose (160 mg/kg; 1/14 LD10), to significantly limit the severity of acute RSR after single (40 Gy) and fractionated (78 Gy) β-ray irradiation. The results confirm T1082 as one of the safest emergency radioprotectors and indicate the prospects for its further development as a pharmacological agent for the prevention of RT complications. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Filimonova M.1 , Saburova A.1 , Shevchenko L.1 , Makarchuk V.1 , Shitova A.1 , Soldatova O.1 , Rybachuk V.1 , Kosachenko A.1 , Nikolaev K.1 , Demyashkin G.1 , Saburov V.1 , Koryakin S.1 , Shegay P.2 , Kaprin A. 2, 3 , Ivanov S. 1, 3 , Filimonov A.1
Publisher
MDPI AG
Number of issue
5
Language
English
Status
Published
Number
2697
Volume
23
Year
2022
Organizations
  • 1 A. Tsyb Medical Radiological Research Center—Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk, 249036, Russian Federation
  • 2 National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk, 249036, Russian Federation
  • 3 Medical Institute (RUDN University), Peoples’ Friendship, University of Russia, Moscow, 117198, Russian Federation
Keywords
Pharmacological safety; Radiation-induced tissue toxicity; Radiotherapy; Selective radiation protection
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