Abstract
WR-2721 (S-2(3-aminopropylaminoethyl) phosphorothioic acid) is an organic thiophosphate derivative of cysteamine which was developed under the auspices of the Walter Reed Army Institute of Research in an attempt to develop non-toxic means of introducing thiol-containing compounds into tissues. Thiols are known to protect cells against the toxic effects of ionizing radiation and alkylating agent chemotherapy, however agents with free sulfhydryl groups such as cysteamine are very toxic. To avert the toxicity of this reactive group, several thioester derivatives were synthesized (1). Yuhas (2) found that one of the thiophosphates, WR-2721, is accumulated by, and provides radioprotection to normal tissues, but not certain tumors in experimental animals. The mechanism of this tissue selectivity is unknown. In studies in animals and humans, there are few side effects at doses providing radioprotection (3). During initial trials of its efficacy as a radio- and a chemoprotective agent in patients with malignancies, acute transient hypocalcemia was noted; intravenous WR-2721 produced a 20% fall in the serum calcium concentration at four hours and serum calcium levels remained depressed at 24 hours. Serum concentrations of immunoreactive PTH were reduced after infusion of WR-2721 instead of increasing in response to hypocalcemia suggesting that WR-2721 causes hypocalcemia by reducing secretion of PTH (4).
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© 1989 Plenum Press, New York
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Attie, M.F., Goldfarb, S., Fallon, M., Shaker, J., Carmichael, K. (1989). Effects of WR-2721 on Parathyroid Hormone Secretion and Bone. In: Massry, S.G., Fujita, T. (eds) New Actions of Parathyroid Hormone. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0567-5_4
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DOI: https://doi.org/10.1007/978-1-4613-0567-5_4
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