6-ethylthioinosine

6-ethylthioinosine (6-ETI) is a novel nucleoside analog and pro-drug that is selectively activated via phosphorylation by adenosine kinase (ADK), an enzyme frequently overexpressed in certain hematological and solid malignancies. Primarily investigated for its activity against plasma cell neoplasms such as primary effusion lymphoma (PEL), multiple myeloma (MM), and plasmablastic lymphoma (PBL), 6-ETI also demonstrates potency against colorectal and pancreatic adenocarcinomas. Its mechanism of action involves the depletion of cellular nucleotide pools and the inhibition of DNA synthesis, leading to S-phase arrest and necrosis. Additionally, 6-ETI treatment is associated with the activation of AMP-activated protein kinase (AMPK) and the subsequent suppression of the PI3K/mTOR/p70S6K signaling axis. High expression of ADK serves as a critical predictive biomarker for therapeutic response, while loss or mutation of ADK is a primary mechanism of resistance.

Other names

6-ethylmercaptopurine riboside