Clinical Evaluation of Puromycin in Human neoplastic Disease

Abstract

Puromycin (Stylomycin) * is an antibiotic obtained from a species of actinomycete, Streptomyces albo-niger.† In addition to its inhibitory action on some Gram-positive and Gram-negative bacteria and on Trypanosoma equiperdum, Trypanosoma cruzi, and Trypanosoma gambiense,‡ it was found to have inhibitory activity against certain tumors.§ Puromycin shows appreciable inhibition against the mammary adenocarcinoma of the C3H mouse, the mammary adenocarcinoma 755 of the C57BL mouse, and a glioblastoma cultivated in the chick embryo. The structure, chemical properties, and synthetic studies of puromycin have been reported by Waller and co-workers⁸ and Baker and his co-workers.⁹ Puromycin is 6-dimethylamino-9-(3'-p-methoxy-L-phenylalanylamino-3'-deoxy-D-ribosyl)-purine (Fig. 1). Toxicity studies in mice indicate the LD₅₀ values of puromycin to be 360 mg/kg. intravenously, 520 mg/kg. intraperitoneally, and 678 mg/kg. orally. Loss of weight was produced by the antibiotic in the mouse. In rats receiving repeated dosages of 25 to 100 mg/kg. parenterally from one to four weeks, evidence of