A composition comprising an effective amount of a PFKFB3 inhibitor for use in the treatment of cancer, wherein the composition comprises an effective amount of a compound of Formula: wherein: X, X 2, and X 3 are each C or CH; X 1 is O; R 10 is selected from the group consisting of H, alkyl, halo, cyano, hydroxyl, aryl, and aralkyl; R 11 is selected from the group consisting of H, alkyl, halo, cyano, hydroxyl, aryl, and aralkyl; A 1, A 2, A 3, A 4, and A 5, are each independently N or CR 12, wherein each R 12 is independently selected from the group consisting of H, alkyl, halo, nitro, cyano, hydroxyl, mercapto, amino, alkylamino, dialkylamino, carboxyl, acyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulfate, and a group having the structure: wherein: X 4 is NR 14, wherein R 14 is selected from the group consisting of H, alkyl, hydroxyl, aralkyl, and aryl; X 5 is selected from the group consisting of O, S, C(R 15) 2, and NR 14, wherein each R 15 is independently selected from the group consisting of H, hydroxyl, alkoxy, alkyl, aralkyl, and aryl; and X 6 is selected from H, alkyl, aralkyl, aryl, heteroaryl, alkylamino, dialkylamino, and alkoxy; or wherein R 10 and one R 12 are together alkylene; Ar 2 is selected from the group consisting of and wherein: each Y 6, Y 7, Y 8, Y 9, Y 10, Y 11, Y 12, Y 13, Y 14, Y 15, Y 16, Y 17, Y 18, and Y 19 is independently selected from the group consisting of N and CR 13, wherein each R 13 is independently selected from the group consisting of H, alkyl, halo, nitro, cyano, hydroxyl, mercapto, amino, alkylamino, dialkylamino, carboxyl, acyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulfate, and a group having the structure: wherein: X 4 is NR 14, wherein R 14 is selected from the group consisting of H, alkyl, hydroxyl, aralkyl, and aryl; X 5 is selected from the group consisting of O, S, C(R 15) 2, and NR 14, wherein each R 15 is independently selected from the group consisting of H, hydroxyl, alkoxy, alkyl, aralkyl, and aryl; and X 6 is selected from H, alkyl, aralkyl, aryl, heteroaryl, alkylamino, dialkylamino, and alkoxy; or wherein R 10 and one R 13 are together alkylene; and wherein at least one of A 1, A 2, A 3, A 4, A 5, Y 6, Y 7, Y 8, Y 9, Y 10, Y 11, Y 12, Y 13, Y 14, Y 15, Y 16, Y 17, Y 18, and Y 19 is N; or a pharamaceutically acceptable salt thereof, wherein the compound of Formula is or wherein the compound of Formula is: X, X 2, and X 3 are each C or CH; X 1 is O; R 10 is selected from the group consisting of H, alkyl, halo, cyano, hydroxyl, aryl, and aralkyl; R 11 is selected from the group consisting of H, alkyl, halo, cyano, hydroxyl, aryl, and aralkyl; A 1, A 2, A 3, A 4, and A 5, are each independently N or CR 12, wherein each R 12 is independently selected from the group consisting of H, alkyl, halo, nitro, cyano, hydroxyl, mercapto, amino, alkylamino, dialkylamino, carboxyl, acyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulfate, and a group having the structure: wherein: X 4 is NR 14, wherein R 14 is selected from the group consisting of H, alkyl, hydroxyl, aralkyl, and aryl; X 5 is selected from the group consisting of O, S, C(R 15) 2, and NR 14, wherein each R 15 is independently selected from the group consisting of H, hydroxyl, alkoxy, alkyl, aralkyl, and aryl; and X 6 is selected from H, alkyl, aralkyl, aryl, heteroaryl, alkylamino, dialkylamino, and alkoxy; each Y 6, Y 7, Y 8, Y 9, Y 10, Y 11, Y 12, Y 13, Y 14, Y 15, Y 16, Y 17, Y 18, and Y 19 is independently selected from the group consisting of N and CR 13, wherein each R 13 is independently selected from the group consisting of H, alkyl, halo, nitro, cyano, hydroxyl, mercapto, amino, alkylamino, dialkylamino, carboxyl, acyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, sulfate, and a group having the structure: wherein: X 4 is NR 14, wherein R 14 is selected from the group consisting of H, alkyl, hydroxyl, aralkyl, and aryl; X 5 is selected from the group consisting of O, S, C(R 15) 2, and NR 14, wherein each R 15 is independently selected from the group consisting of H, hydroxyl, alkoxy, alkyl, aralkyl, and aryl; and X 6 is selected from H, alkyl, aralkyl, aryl, heteroaryl, alkylamino, dialkylamino, and alkoxy;