A polycomb repressive complex 1 inhibitor of Formula: wherein A, A' form a AA' bicyclic ring system, wherein said bicyclic ring sytem is an 1H-indole ring; wherein E, and E' are independently selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl rings that are linked to form a bicyclic ring system EE'; wherein R 2 is an aliphatic group, haloalkyl, cycloalkyl, or substituted cycloalkyl; wherein R 4 is (CH 2) 0-5 COOH, (CH 2) 0-6 OH, tetrazole, -(CH 2) 0-5 C NH 2, -(CH 2) 0-5 C NH(CH 2) 0-3, -C O(CH 2) 1-4 (CH 3), -(CH 2) 0-5 SO 2 NH 2, -(CH 2) 0-5 SO 2 CH 3, or -NHSO 2 NH 2; wherein X is, NH, NR 5, or S; wherein R 5, when present, is straight of branched alkyl (e.g. CH 3), (CH 2) 1-6 -COOH, (CH 2) 1-6 -CONH 2, (CH 2) 1-6 -SO 2 NH 2, (CH 2) 1-6 -OH, NH 2, substituted alkyl, heteroalkyl, substituted heteroalkyl, cycloalkyl, substituted cycloalkyl, amide; wherein R A1-5, R A'1-5, R E1-5, and R E'1-5 may be absent or present, may be located at any position on the bicyclic ring system, may be present simultanneously at more than one position, and when present is selected from C 1 -C 8 alkyl, C 1 -C 8 branched alkyl, substituted alkyl, haloalkyl, C 1 -C 8 alkoxy, -OCF 3, -OH, -(CH 2) 1-6 OH, -OR 6, -(CH 2) 1-6 OR 6, amide, substituted amide, -NH 2, substituted amine (-NHR 6), -(CH 2) 1-6 NHR 6, -(CH 2) 0-6 SR 6, carboxy, sulfonamide, substituted sulfonamide, sulphone, phosphonate, -SH, -CN, halogen, aryl, heteroaryl or a ring of selected from the following: and wherein R 6, when present, is C 1 -C 8 alkyl, C 1 -C 8 branched alkyl, alkyne, alkene, substituted alkyl, haloalkyl, C 1 -C 8 alkoxy, -(CH 2) 1-6 OH, ether, amide, amine, substituted amine, C 3 -C 8 saturated non-aromatic ring substituted or non-substituted, C 3 -C 8 heterocyclic saturated ring, aryl, heteroaryl or a ring of selected from the following: wherein A, A' form a AA' bicyclic ring system, wherein said bicyclic ring sytem is an 1H-indole ring; wherein E, and E' are independently selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl rings that are linked to form a bicyclic ring system EE'; wherein R 2 is an aliphatic group, haloalkyl, cycloalkyl, or substituted cycloalkyl; wherein R 4 is (CH 2) 0-5 COOH, (CH 2) 0-6 OH, tetrazole, -(CH 2) 0-5 C NH 2, -(CH 2) 0-5 C NH(CH 2) 0-3, -C O(CH 2) 1-4 (CH 3), -(CH 2) 0-5 SO 2 NH 2, -(CH 2) 0-5 SO 2 CH 3, or -NHSO 2 NH 2; wherein X is, NH, NR 5, or S; wherein R 5, when present, is straight of branched alkyl (e.g. CH 3), (CH 2) 1-6 -COOH, (CH 2) 1-6 -CONH 2, (CH 2) 1-6 -SO 2 NH 2, (CH 2) 1-6 -OH, NH 2, substituted alkyl, heteroalkyl, substituted heteroalkyl, cycloalkyl, substituted cycloalkyl, amide; wherein R A1-5, R A'1-5, R E1-5, and R E'1-5 may be absent or present, may be located at any position on the bicyclic ring system, may be present simultanneously at more than one position, and when present is selected from C 1 -C 8 alkyl, C 1 -C 8 branched alkyl, substituted alkyl, haloalkyl, C 1 -C 8 alkoxy, -OCF 3, -OH, -(CH 2) 1-6 OH, -OR 6, -(CH 2) 1-6 OR 6, amide, substituted amide, -NH 2, substituted amine (-NHR 6), -(CH 2) 1-6 NHR 6, -(CH 2) 0-6 SR 6, carboxy, sulfonamide, substituted sulfonamide, sulphone, phosphonate, -SH, -CN, halogen, aryl, heteroaryl or a ring of selected from the following: and wherein R 6, when present, is C 1 -C 8 alkyl, C 1 -C 8 branched alkyl, alkyne, alkene, substituted alkyl, haloalkyl, C 1 -C 8 alkoxy, -(CH 2) 1-6 OH, ether, amide, amine, substituted amine, C 3 -C 8 saturated non-aromatic ring substituted or non-substituted, C 3 -C 8 heterocyclic saturated ring, aryl, heteroaryl or a ring of selected from the following: