The organic extract of the fermentation broth of an unidentified fungus was found to contain three epidermal growth factor (EGF) receptor antagonists: SCH 64874 (1), SCH 64875 (2), SCH 64877 (3). These compounds belong to a family of thiodiketopiperazine derivatives and are esters of an eight carbon aliphatic acid, 2,4-dimethyl-3- hydroxyhexanoic acid and a thiodiketopiperazine, aranotin, They exhibited potent EGF receptor antagonist activity. The ICs0 in EGF receptor assays for compounds l, 2 and 3 are 1.0, 1.0 and 1.25 gg/ml, respectively. © 1997, Elsevier Science Ltd. All rights reserved.