# US 2021/0228583 A1 · Methods and Compositions for Reducing Radiation Induced Toxicity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0228583 A1 - Document ID: US20210228583A1 - Status: Published application - Kind: A1 - Application number: 17/175,227 - Filed: 2021-02-12 - Published: 2021-07-29 - Earliest claimed: 2018-08-14 - Assignees: Tosk, Inc. - Applicants: Tosk, Inc. - Inventors: William A. Garland; Brian D. Frenzel; Philip Liaw - Web page: https://patentgrep.com/patent/US20210228583A1 ## CPC - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine - A61P 39/00: General protective or antinoxious agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Methods for reducing radiation therapy induced toxicity, e.g., mucositis, in a subject are provided. Aspects of the methods include administering an effective amount of a radiation toxicity-reducing adjuvant to the subject. In certain embodiments, the radiation toxicity-reducing adjuvant is a 2,2′-anhydropyrimidine, or a derivative thereof. Also provided are compositions for use in practicing the subject methods. The subject methods and compositions find use in a variety of different applications, including the treatment of a variety of different disease conditions. ## Claims ### Claim 1 A method of reducing radiation therapy induced toxicity in a subject, the method comprising: administering to the subject an effective amount of a 2,2′-anhydropyrimidine or derivative thereof to reduce radiation therapy induced toxicity in the subject. ### Claim 2 (depends on 1) The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is a compound of formula (I): or the pharmaceutically acceptable salts, solvates, hydrates, and prodrug forms thereof, and stereoisomers thereof; wherein: each R1, R2, R3 and R4 is independently selected from the group consisting of hydrogen, substituted or unsubstituted heteroatom, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, carbohydrate, nucleic acid, amino acid, peptide, dye, fluorophore and polypeptide. ### Claim 3 (depends on 2) The method according to claim 2, wherein each R1, R2, R3 and R4 is independently selected from the group consisting of hydrogen, hydroxyl, sulfyhydryl, amino, hydroxymethyl, methoxy, halogen, pseudohalogen, and a substituted or unsubstituted lower hydrocarbon containing 1 to 20 carbons. ### Claim 4 (depends on 2) The method according to claim 2, wherein the lower hydrocarbon is selected from the group consisting of alkyl, alkenyl, alkanoyl, aryl, aroyl, aralkyl and alkylamino, and esters thereof. ### Claim 5 (depends on 2) The method according to claim 2, wherein R1 is hydrogen, fluorine, methyl, ethyl, propyl, benzyl, or 2-bromovinyl; R2 is hydrogen, hydroxyl fluorine, methyl, ethyl, propyl, benzyl, benzoyl, benzoyloxy, or 2-bromovinyl; and each R3 and R4 is independently selected from the group consisting of hydroxyl and benzoyloxy. ### Claim 6 (depends on 5) The method according to claim 5, wherein R1 is hydrogen or methyl; R2 is hydrogen; and each R3 and R4 is independently selected from the group consisting of hydroxyl and benzoyloxy. ### Claim 7 (depends on 1) The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is selected from the group consisting of: 2,2′-anhydro-5-methyluridine; 3′-O-benzoyl-2,2′-anhydrouridine; 3′-O-benzoyl-2,2′-anhydro-5-methyluridine; 5′-O-benzoyl-2,2′-anhydrouridine; and 5′-O-benzoyl-2,2′-anhydro-5-methyluridine. ### Claim 8 (depends on 7) The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 2,2′-anhydro-5-methyluridine. ### Claim 9 (depends on 7) The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 3′-O-benzoyl-2,2′-anhydro-5-methyluridine. ### Claim 10 (depends on 7) The method according to claim 7, wherein the 2,2′-anhydropyrimidine or derivative thereof is 5′-O-benzoyl-2,2′-anhydro-5-methyluridine. ### Claim 11 (depends on 1) The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof comprises a stereoisomer. ### Claim 12 (depends on 11) The method according to claim 11, wherein the stereoisomer is selected from the group consisting of 2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil; 3′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-uracil; 3′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil; 5′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-uracil; and 5′-O-benzoyl-2,2′-anhydro-1-(β-D-arabinofuranosyl)-5-methyluracil. ### Claim 13 (depends on 1) The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is administered to the subject at the same time as radiation therapy. ### Claim 14 (depends on 1) The method according to claim 1, wherein the 2,2′-anhydropyrimidine or derivative thereof is administered to the subject sequentially with radiation therapy. ### Claim 15 (depends on 14) The method according to claim 14, wherein the 2,2′-anhydropyrimidine or derivative thereof is administered to the subject prior to the radiation therapy. ### Claim 16 (depends on 14) The method according to claim 14, wherein the 2,2′-anhydropyrimidine or derivative thereof is administered to the subject after the radiation therapy. ### Claim 17 (depends on 1) The method according to claim 1, wherein the method reduces crypt cell loss as compared to a suitable control. ### Claim 18 (depends on 1) The method according to claim 1, wherein the radiation therapy induced toxicity is mucositis. ### Claim 19 (depends on 1) The method according to claim 1, wherein the subject is suffering from a cellular proliferative disease. ### Claim 20 (depends on 1) The method according to claim 1, wherein a greater radiation therapy is administered to the subject as compared to a suitable control.