Methods and compositions for modulating gene expression

An agent having a formula A-L-B, wherein:

• -L- is a linker;
• A- is a Brd4 binding moiety selected from the group consisting of triazolodiazepines having a structure
• wherein:
• J is N, O or CR11;
• K is N, O or CR11;
• with the proviso that J and K cannot both be —O—;
• P is N, except when one of J or K is —O—, P is C, wherein R11 is a hydrogen or optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group,
• R1 is a hydrogen or optionally substituted alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, halogenated alkyl, hydroxyl, alkoxy, or —COOR4, wherein R4 is a hydrogen, substituted or unsubstituted arylene, aralkylene, cycloalkylene, heteroarylene, heteroaralkylene, heterocycloalkylene, alkylene, alkenylene, alkynylene, or cycloalkylalkylene group optionally interrupted by one or more heteroatoms,
• R2 is an optionally substituted aryl, alkyl, cycloalkyl, or aralkyl group,
• R3 and R10 are each independently a hydrogen, halogen, or optionally substituted alkyl group,
• “x” is an integer of from 1 to 10, and
• Ring E is an optionally substituted aryl or heteroaryl ring;
• and
• thienotriazolodiazepines having a structure
• wherein:
• R2 is an aryl group optionally substituted with one or more substituted or unsubstituted alkyl, alkenyl, alkynyl, halogen, —OR6, —SR6, —N(R6)2, —N(R6)COR9 groups, wherein R6 and R9 are independently a hydrogen or alkyl group,
• R1 and R3 are independently a hydrogen or optionally substituted alkyl group,
• R5 and R7 are each independently a hydrogen, alkyl, alkenyl, alkynyl, halogen, halogenated alkyl, —OH, —SH, or —NH2, and
• “x” is an integer of from 1 to 10;
• and
• —B is a nucleic acid binding moiety that specifically binds to one or more repeats of a target oligonucleotide sequence selected from the group consisting of CGG, CTG, and CCTG.