Modern Condition and Prospects for the Development of Medicines towards Prevention and Early Treatment of Radiation Damage

Abstract

An analysis of the current status and future directions of developing medicines for the prevention and early treatment of radiation damage has been conducted. Among radioprotectors, only B-190 (Indralin) is approved for use in the Russian Federation; the main radioprotector in foreign countries is amifostine (Ethyol). Some prospects in the development of new radioprotectors are associated with inhibitors of NO-synthases from the class of N-acyl-S-alkyl-substituted isothiourea derivatives, among which chemical compounds with a pronounced radioprotective effect are found. A recombinant human interleukin-1β (Betaleukin) has been registered in Russia as a radiomitigator intended for use in the early period after accidental irradiation. The US Food and Drug Administration (FDA) has approved the investigational new drug status for seven radiomitigators, including 5-androstenediol (Neumune), genistein (BIO 300), CBLB502 (Entolimod), a kinase inhibitor ON01210 (Ex-RAD), recombinant human interleukin-12 (HemaMax), beclomethasone (OrbeShield), and a granulocyte colony-stimulating factor (G-CSF, Neupogen). Ondansetron hydrochloride dihydrate (Latran) was registered as an antiemetic drug for prevention and therapy of the primary response to radiation in Russia, and granisetron (Kytril) was registered as an antiemetic drug upon irradiation abroad. Potassium iodide, potassium ferric hexacyanoferrate (Ferrocin), diethylenetriaminepentaacetate calcium trisodium (Pentacin, calcium trisodium pentetate), and 2,3-dimercaptopropansulfonate sodium (Unithiol) are used in Russia for the prevention and treatment of damage from irradiation via incorporated radionuclides. Potassium iodide (ThyroShield), diethylenetriaminepentaacetate zinc trisodium (Zn-DTPA, Pentetate zinc trisodium), diethylenetriaminepentaacetate calcium trisodium (Ca-DTPA, Pentetate calcium trisodium), and ferric hexacyanoferrate (Prussian blue, Radiogardase) are used as decorporation agents abroad. Cytokines, vitamins, low-molecular compounds, inhibitors of apoptosis, etc., are considered promising means for the prevention and early treatment of radiation damage.