View article

LY309887, a reduced analogue of folic acid, is a potent inhibitor of glycinamide ribonucleotide formyltransferase and possesses a broad spectrum of antitumor activity. During preclinical studies using supplementation with oral folic acid, this second-generation inhibitor displayed both the desired safety profile and the pharmacology to warrant clinical investigation. A sensitive analytical method was needed to assess the pharmacokinetics of LY309887 due to the low doses planned for Phase I studies and the potential for low concentrations in plasma long after i.v. administration. We therefore undertook the development of a competitive RIA. A highly specific antiserum was raised in rabbits following immunization with LY309887 coupled to BSA. A RIA tracer was prepared by radioiodination of compound 389753, the adduct of LY309887 with p-tyramine. We developed a competitive-binding RIA procedure and used …