FOLR2 and neoplasm: These agents selectivelytarget cells(including tumor cells) expressing FRα or FRβ while notaffecting cells that express RFC or PCFT.25 These analogs are structurally and functionally distinct from PMX,a 5-substituted pyrrolo[2,3-d]pyrimidine antifolate,6 as well as previously reported 6-substitutedpyrrolo[2,3-d]pyrimidine antifolates.26−30 Isosteric replacement of the fused pyrrole ring with a thiophenering provides an increase in the ring size that more closely resemblesthe 6–6 fused pteridine ring system of naturally occurringfolate cofactors.