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Busulfan, a common name for the dimethanesulfonate ester of 1,4-butanediol, is an older chemotherapy drug sold under the trade names Myleran, Busulfex, and many others. It was described as a leukemia treatment by inventor Geoffrey M. Timmins in a 1959 US Patent to Burroughs Wellcome (Tuckahoe, NY; now part of GlaxoSmithKline).
Busulfan’s mode of action is as a bifunctional alkylating agent, which has an immunosuppressive effect on bone marrow. It stops tumor growth by cross-linking guanine bases in DNA double-helix strands. This makes the strands unable to uncoil and separate. Because this process is necessary for DNA replication, the tumor cells can no longer divide. In addition, busulfan adds methyl groups where they do not belong, which leads to DNA miscoding.
Almost a decade before the Timmins patent was issued, busulfan was implicated in the death of a 67-year-old breast cancer patent. An anonymous 1950 article in the British Medical Journal titled “Death after new drug” compared busulfan to the properties of nitrogen mustards, war gases that were also being tried as anticancer agents. The article suggested that busulfan behaved anomalously in the body compared with other compounds with similar properties.
Despite this mishap and its dangerous properties (see the hazard information table), busulfan continued to be developed as a cancer drug. In 1999, it was approved by the US Food and Drug Administration for treating chronic myeloid leukemia. Its use was soon reduced because of the emergence of Novartis’s imatinib1, which was approved by the FDA for treating cancer 2 years after busulfan. Imitanib, however, has its own adverse effects and is more expensive, and busulfan is still on the market. It is currently listed as an orphan drug by the FDA.
1. CAS Reg. No. 152459-95-5.
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