acylfulvene-derived prodrug LP-184

A tumor-site activated acylfulvene-derived prodrug and alkylating agent, with potential antineoplastic activity. Upon administration, acylfulvene-derived prodrug LP-184 becomes activated by prostaglandin reductase 1 (PTGR1), an oxidoreductase that is specifically upregulated in certain tumor cell types. The active form of LP-184 covalently binds to and alkylates DNA at N3-adenine, thereby causing double strand breaks. As tumor cells often carry DNA damage repair (DDR) mutations and are therefore deficient in DDR pathways, the DNA damage cannot be repaired. In turn, the damaged DNA causes apoptosis and inhibits proliferation in susceptible DDR mutated tumor cells. PTGR1 is often elevated in solid tumors but not in normal tissues.