BTdCPU is acts as an inhibitor of the formation of the ternary complex of eukaryotic translation initiation factor 2 (eIF2), GTP and the initiator methionine tRNA (Met-tRNAi), a key regulatory step of translation initiation.
BTdCPU is a potent heme-regulated eIF2α kinase (HRI) activator and promotes eIF2α phosphorylation. BTdCPU induces apoptosis in resistant cell. Combination therapy with rapamycin, an mTOR inhibitor, and BTdCPU, an activator of HRI (heme-regulated eIF2α kinase), demonstrated additive effects on apoptosis in dex-resistant cells. Thus, specific activation of the eIF2α kinase HRI is a novel therapeutic target in MM that can augment current treatment strategies[1]. Treatment with 100, 200 or 350 mg per kg body weight per day of BTdCPU had no discernable adverse effect on weight gain, and mice did not show any outward signs of toxicity, even at the highest dose. Administration of 175 mg per kg per day of BTdCPU caused total tumor stasis starting 1 week after the first injection. Treatment with compound BTdCPU significantly elevated phosphorylation of eIF2α[2].
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