Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) using S-adenosyl-L-methionine as the methyl donor. TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified. S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether. mercaptopurine + S-adenosyl-L-methionine = 6-methylthiopurine + H(+) + S-adenosyl-L-homocysteine Monomer. Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.