A new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses

International Journal of Radiation Oncology Biology Physics

Volumn 82, Issue 5, 2012, Pages

  Soref, Cheryl M ^a   Hacker, Timothy A ^b   Fahl, William E ^a,c  

^a ProCertus BioPharm Inc   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^c UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Amifostine toxicity; Aminothiol; Oral radioprotection; PrC 210; Survival assay

Indexed keywords

AMIFOSTINE; AMINOTHIOLS; BODY WEIGHT; DRUG DEVELOPMENT; EQUIVALENT DOSE; HEALTHY HUMANS; INTRAPERITONEAL; MAXIMUM TOLERATED DOSE; MOUSE MODELS; NUCLEAR ACCIDENTS; ORALLY ACTIVE; PRC-210; RADIOPROTECTION; SIDE EFFECT; SPACE TRAVEL; WHOLE-BODY;

ANIMALS; IRRADIATION;

RATS;

AMIFOSTINE; AMINOTHIOL; LOPERAMIDE; PRC 210; RADIOPROTECTIVE AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTERY CATHETERIZATION; ARTICLE; BLOOD PRESSURE MONITORING; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EFFECT; DRUG FECES LEVEL; DRUG MEGADOSE; FEEDING; FEMALE; FERRET; HYPOTENSION; LETHALITY; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RADIATION DOSE; RADIATION PROTECTION; RAT; RETCHING; SURVIVAL RATE; SURVIVAL TIME; SYNCOPE; TIME TO MAXIMUM PLASMA CONCENTRATION; WHOLE BODY RADIATION;

ADMINISTRATION, ORAL; AMIFOSTINE; ANIMALS; DIAMINES; DRUG EVALUATION, PRECLINICAL; FEMALE; FERRETS; HYPOTENSION; INFUSIONS, INTRA-ARTERIAL; INFUSIONS, PARENTERAL; INJECTIONS, SUBCUTANEOUS; MALE; MAXIMUM TOLERATED DOSE; MICE; MICE, INBRED ICR; NAUSEA; RADIATION INJURIES, EXPERIMENTAL; RADIATION-PROTECTIVE AGENTS; RATS; RATS, SPRAGUE-DAWLEY; SULFHYDRYL COMPOUNDS; VOMITING;

EID: 84858706707     PISSN: 03603016     EISSN: 1879355X     Source Type: Journal    
DOI: 10.1016/j.ijrobp.2011.11.038     Document Type: Article

References (19)

1. Weiss JF, Landauer MR. History and development of radiationprotective agents. Int J Radiat Biol Phys 2009;85:539-573.
2. Winczura P, Jassem J. Combined treatment with cytoprotective agents and radiotherapy. Cancer Treat Rev 2010;36:268-275.
3. Augustine AD, Gondré-Lewis T, McBride W, et al. Animal models for radiation injury, protection and therapy. Radiat Res 2005;164:100-109. (Pubitemid 40885234)
4. Langell J, Jennings R, Clark J, et al. Pharmacological agents for the prevention and treatment of toxic radiation exposure in spaceflight. Aviat Space Environ Med 2008;79:651-660. (Pubitemid 351915299)
5. American Society of Clinical Oncology. 2008 clinical practice guideline update: Use of chemotherapy and radiation therapy protectants. J Clin Oncol 2009;27:127-145.
6. Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: Results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996;14:2101-2112. (Pubitemid 26230113)
7. Rose PG. Amifostine cytoprotection with chemotherapy for advanced ovarian carcinoma. Semin Oncol 1996;23(4 Suppl. 8):83-89. (Pubitemid 26321678)
8. Kligerman MM, Turrisi AT 3rd, Urtasun RC, et al. Final report on phase I trial of WR-2721 before protracted fractionated radiation therapy. Int J Radiat Oncol Biol Phys 1988;14:1119-1122.
9. Ethyol package insert. http://www.ethyol.com/resources/pdf/Ethyol-PI.pdf.
10. Verhey LJ, Sedlacek R. Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin. Radiat Res 1983;93:175-183. (Pubitemid 13180401)
11. Montana GS, Anscher MS, Mansbach CM, et al. Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis. A Phase I/II trial. Cancer 1992;69:2826-2830.
12. Fahl WE, Peebles DD, Copp RR. Amino thiol compounds and compositions for use in conjunction with cancer therapy. United States patent US 7,314,959.
13. Peebles DD, Soref CM, Copp RR, et al. ROS-Scavenger and Radioprotective Efficacy of the New PrC-210 Aminothiol. Radiat Res. In press.
14. Copp RR, Peebles DD, Fahl WE, et al. Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors. Bioorg Med Chem Lett 2011;21: 7426-7430.
15. Copp RR, Peebles DD, Soref CM, et al. Radioprotection conferred by a new family of aminothiol analogs. (submitted).
16. Chu KM, Ngan MP, Wai MK, et al. Olvanil: A non-pungent TRPV1 activator has anti-emetic properties in the ferret. Neuropharmacology 2010;58:383-391.
17. Bogdanich W. Radiation offers new cures, and ways to do harm. The New York Times; 2010 Jan 23, http://www.nytimes.com/2010/01/24/ health/24radiation. html.
18. du Sert NP, Holmes AM, Wallis R, et al. Predicting the emetic liability of novel chemical entities: A comparative study. Br J Pharmacol 2011;1476-1481.
19. Einstein AJ, Moser KW, Thompson RC, et al. Radiation dose to patients from cardiac diagnostic imaging. Circulation 2007;116: 1290-1305. (Pubitemid 47517541)