Identification of Small Molecule Inhibitors of Jumonji AT-Rich Interactive Domain 1A (JARID1A) and 1B (JARID1B) Histone Demethylase

摘要

The present invention includes a novel high-throughput screen capable of identifying compounds that inhibit JARID1B demethylase activity or JARID1A demethylase activity. The present invention further includes novel inhibitors of JARID1B demethylase activity and/or JARID1A demethylase activity, and methods using the same.

主权项

1. A pharmaceutical composition comprising a compound, or a salt or solvate thereof, selected from the group consisting of:
caffeic acid; esculetin; a compound of formula (I):
wherein in formula (I):R1 is S, O, NH or N(C1-C6 alkyl);R2 is N, CH or C—(C1-C6 alkyl); andn is 0, 1, 2, 3 or 4, wherein each occurrence of R3 is independently selected from the group consisting of C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, substituted heteroaryl, halogen, C1-C6 alkoxy, nitro, amino, acetamido, hydroxy and carboxy; a compound of formula (II): wherein in formula (II):R1 is C1-C6 alkyl, substituted C1-C6 alkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heretocyclyl, acyl, benzoyl, substituted benzoyl or phenylacetyl;R2 is C(R4)2, O, S, C(O), S(O), S(O)2 or Se;n is 0, 1, 2, 3 or 4, wherein:
each occurrence of R3 is independently selected from the group consisting of C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, substituted C3-C7 cycloalkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, substituted heteroaryl, halogen, C1-C6 alkoxy, nitro, amino, acetamido, hydroxy, cyano and carboxy; andeach occurrence of R4 is independently H, C1-C6 alkyl, or substituted C1-C6 alkyl;