The subject invention concerns methods and compounds for inhibiting Shp2. In one embodiment, a compound of the invention has a chemical structure as shown in formula I or II: wherein X, Y, and Z are independently N or S; R1 is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, any of which can be optionally substituted with one or more of halogen; alkyl; heteroalkyl; —COOH; —C(R3)3, wherein R3 can independently be any of —H or halogen; or —OR4, wherein R4 can be any of H, alkyl, or heteroalkyl; R2 is alkyl, alkylcarbonyl, heteroalkylcarbonyl, aryl, arylcarbonyl, heterocycloalkylcarbonyl, cycloalkylcarbonyl, or —C(O)NR6R7, any of which can be optionally substituted with one or more of halogen; alkyl; heteroalkyl; carbonyl; —OR4, wherein R4 can be —H, alkyl, or heteroalkyl; —OH; —C(R3)3, wherein R3 can independently be any of —H or halogen; aryl, which can be substituted with one or more of halogen or —OR4; heterocycloalkyl; or —C(O)OR5, wherein R5 can be —H or alkyl; R6 and R7 are independently —H, alkyl, heteroalkyl, aryl, or heteroaryl; and R′ is H or alkyl; or a pharmaceutically acceptable salt or hydrate thereof.