VITALETHINE MODULATES ERYTHROPOIESIS AND NEOPLASIA

Novel compounds based upon the thiol N-(carboxy)-beta-alanyl-cysteamin e (vitaletheine) have strikingly potent and seemingly diverse biologic al activities. Concentrations of vitaletheine modulators from 1 femtog rams/ml to 100 picograms/ml medium regulate RBC production from progen itors initially deprived of erythropoietin. Similarly, as little as at tograms/ml concentrations of the disulfide vitalethine stimulate immun ological responses of murine splenocytes toward sheep RBC in a hemolyt ic plaque assay. Because dosages of vitalethine as low as femtograms/k g substantially diminish tumor size and incidence and increase surviva l to 80% in mice inoculated with a uniformly fatal melanoma (Cloudman S-91), activities of these compounds have in vivo significance. A prel iminary probe of the benzyl derivative of vitalethine in a myeloma mod el (NS-1) suggests efficacy (100% survival) as well. The high potencie s of the vitaletheine modulators, both in cell culture and in vivo, in dicate that these or similar regulatory components, if constitutively present, probably occur endogenously at vanishingly small concentratio ns and may be prone to deficiency resulting from metabolic imbalances, irradiation, aging, diet, pathogenic or parasitic infections, or expo sure to environmental pollutants. pathways for the biosynthesis of vit aletheine are proposed and chemical syntheses of the vitaletheine modu lators are described. Possible molecular mechanisms of action, includi ng interactions with peptidyl hormones, other endogenous effecters, an d xenobiotic and pharmaceutical compounds, are explored. Indications f or the treatment of other diseases are identified.