A compound having structural formula I: or a pharmaceutically acceptable salt or tautomer thereof, wherein: Z is C(R 9) or N; one of Y 1 or Y 2 is N and the other is C; one of X 1, X 2, X 3, or X 4 is N and each of the others is independently C(R 5); each of R 1, R 2 and R 9 is independently selected from hydrogen, halo, -OH, -CN, C 1 -C 4 alkyl, -O-(C 1 -C 4 alkyl), -N(R 7) 2, -(C 0 -C 4 alkylene)-aryl, -(C 0 -C 4 alkylene)-heteroaryl, -(C 0 -C 4 alkylene)-heterocyclyl, and -(C 0 -C 4 alkylene)-carbocyclyl; or R 1 and R 9 are taken together with atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl ring; or R 2 and R 9 are taken together with atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl ring; each of R 3, R 4 and R 5 is independently selected from hydrogen, halo, -CN, -(C 0 -C 4 alkylene)-R 8, -(C 2 -C 6 alkenylene or alkynylene)-R 6, -(C 1 -C 4 alkylene)-O-R 6, -(C 1 -C 4 alkylene)-O-(C 1 -C 4 alkylene)-R 8, -O-(C 0 -C 4 alkylene)-R 6, -O-(C 2 -C 4 alkylene)-O-R 8, -O-(C 1 -C 4 alkylene)-R 6, -(C 0 -C 4 alkylene)-N(R 7) 2, -(C 0 -C 4 alkylene)-C -O-R 6, -(C 0 -C 4 alkylene)-O-C -R 6, -(C 0 -C 4 alkylene)-C -N(R 7) 2, -(C 0 -C 4 alkylene)-N(R 7)-C -R 6, -O-(C 1 -C 4 alkylene)-C -N(R 7) 2, -O-(C 2 -C 4 alkylene)-N(R 7)-C -(R 7), -(C 0 -C 4 alkylene)-S -R 8, -(C 0 -C 4 alkylene)-S 2 -R 8, -(C 0 -C 4 alkylene)-S 2 -N(R 7) 2, -(C 0 -C 4 alkylene)-N(R 7)-S 2 -R 8, and -(C 0 -C 4 alkylene)-C -R 8; each R 6 is independently selected from hydrogen or R 8; each R 7 is independently selected from hydrogen, -(C 0 -C 4 alkylene)-R 6, -(C 0 -C 4 alkylene)-O-R 6, -S 2 -R 8, -C(=O)-R 8, -C(=O)-N(R 6) 2, -(C 1 -C 4 alkylene)-O-C(=O)-R 8 and -(C 0 -C 4 alkylene)-C(=O)-O-R 6; or two R 7 are taken together with the nitrogen atom to which they are commonly bound to form an optionally substituted heterocyclyl or heteroaryl; R 8 is selected from C 1 -C 4 alkyl, aryl, heteroaryl, carbocyclyl and heterocyclyl; wherein unless otherwise designated any alkyl, alkylene, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl or carbocyclyl portion of the compound is optionally substituted. Z is C(R 9) or N; one of Y 1 or Y 2 is N and the other is C; one of X 1, X 2, X 3, or X 4 is N and each of the others is independently C(R 5); each of R 1, R 2 and R 9 is independently selected from hydrogen, halo, -OH, -CN, C 1 -C 4 alkyl, -O-(C 1 -C 4 alkyl), -N(R 7) 2, -(C 0 -C 4 alkylene)-aryl, -(C 0 -C 4 alkylene)-heteroaryl, -(C 0 -C 4 alkylene)-heterocyclyl, and -(C 0 -C 4 alkylene)-carbocyclyl; or R 1 and R 9 are taken together with atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl ring; or R 2 and R 9 are taken together with atoms to which they are bound to form an aryl, heteroaryl, heterocyclyl, or carbocyclyl ring; each of R 3, R 4 and R 5 is independently selected from hydrogen, halo, -CN, -(C 0 -C 4 alkylene)-R 8, -(C 2 -C 6 alkenylene or alkynylene)-R 6, -(C 1 -C 4 alkylene)-O-R 6, -(C 1 -C 4 alkylene)-O-(C 1 -C 4 alkylene)-R 8, -O-(C 0 -C 4 alkylene)-R 6, -O-(C 2 -C 4 alkylene)-O-R 8, -O-(C 1 -C 4 alkylene)-R 6, -(C 0 -C 4 alkylene)-N(R 7) 2, -(C 0 -C 4 alkylene)-C -O-R 6, -(C 0 -C 4 alkylene)-O-C -R 6, -(C 0 -C 4 alkylene)-C -N(R 7) 2, -(C 0 -C 4 alkylene)-N(R 7)-C -R 6, -O-(C 1 -C 4 alkylene)-C -N(R 7) 2, -O-(C 2 -C 4 alkylene)-N(R 7)-C -(R 7), -(C 0 -C 4 alkylene)-S -R 8, -(C 0 -C 4 alkylene)-S 2 -R 8, -(C 0 -C 4 alkylene)-S 2 -N(R 7) 2, -(C 0 -C 4 alkylene)-N(R 7)-S 2 -R 8, and -(C 0 -C 4 alkylene)-C -R 8; each R 6 is independently selected from hydrogen or R 8; each R 7 is independently selected from hydrogen, -(C 0 -C 4 alkylene)-R 6, -(C 0 -C 4 alkylene)-O-R 6, -S 2 -R 8, -C(=O)-R 8, -C(=O)-N(R 6) 2, -(C 1 -C 4 alkylene)-O-C(=O)-R 8 and -(C 0 -C 4 alkylene)-C(=O)-O-R 6; or two R 7 are taken together with the nitrogen atom to which they are commonly bound to form an optionally substituted heterocyclyl or heteroaryl; R 8 is selected from C 1 -C 4 alkyl, aryl, heteroaryl, carbocyclyl and heterocyclyl;