Tocladesine

Tocladesine is a small molecule antimetabolite and a chlorine derivative of the intracellular secondary messenger cyclic adenosine 3,5-monophosphate (cAMP), developed as an investigational antineoplastic agent. It acts as an analog of cAMP and is converted in cells to 8-chloro-adenosine, which is further phosphorylated to form 8-chloro-ATP. This metabolite functions as a purine analogue, competing with ATP in transcription processes, depleting endogenous ATP pools essential for cellular energy transfer. The resulting effects include inhibition of RNA synthesis, blockade of cellular proliferation, and induction of apoptosis. Tocladesine preferentially binds the R2 subunit of protein kinase A (PKA), modulating signal transduction pathways that lead to growth inhibition and cell differentiation. It also activates AMP‑activated protein kinase (AMPK) with downstream activation of p38 MAPK signaling, contributing to its pro-apoptotic effects. Tocladesine has shown selectivity for cancer cells over normal cells in preclinical studies and was evaluated in phase I/II clinical trials for multiple myeloma, plasma cell neoplasms, colorectal cancer, and other cancers[1][2][3][4][5].

Brand names

Adenazole

Other names

8-chloroadenosine-3',5'-cyclic-monophosphate