DL-Buthionine-(S,R)-sulfoximine hydrochloride (Buthionine sulfoximine hydrochloride) is a potent and specific inhibitor of glutamylcysteine synthetase biosynthesis.

Buthionine sulfoximine is an analog of methionine sulfoximine that inhibits gamma-glutamylcysteine synthetase about 20 times more effectively than prothionine sulfoximine and at least 100 times more effectively than methionine sulfoximine [1].

Treatment of mice bearing HT1080 and HT1080/DR4 xenografts with a continuous i.v infusion of nontoxic doses of D,L-Buthionine-(S,R)-sulfoximine (300 and 600 mg/kg/day) reduced GSH plasma levels by 60% and GSH tumor levels by over 95% in both parental and multidrug-resistant tumors. Combining D,L-Buthionine-(S,R)-sulfoximine with a maximum tolerated dose of doxorubicin administered 24 hours into a 48-hour i.v. infusion of D,L-Buthionine-(S,R)-sulfoximine fully restored the response of MRP-expressing HT1080/DR4 tumors to doxorubicin (overall response rate, 63%; complete response rate, 38%) without increasing host toxicity [2].