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

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) produce a 60% reduction of GSH plasma levels and greater than 95 % reduction in GSH tumor levels in both parental and multidrug-resistant tumors. Under these treatment conditions, a combination of D,L-Buthionine-(S,R)-sulfoximine with the maximum tolerated dose of doxorubicin administered at 24 h during a 48-h i.v. infusion of D,L-Buthionine-(S,R)-sulfoximine completely restored the response of MRP-expressing HT1080/DR4 tumors to doxorubicin (overall response rate, 63%; complete response rate, 38%) with no potentiation of host toxicity [2].