Bifunctional chimeric molecules for labeling of kinases with target binding moieties and methods of use thereof

A chimeric small molecule according to the formula A-L1-E-B or A-L1-E-L2-B,

• wherein A is a kinase protein binding moiety selected from the group consisting of FKBP, PKC, AMPK, ABL, PK, IRTK, MAPK, p38a MAPK, EGFR, FGFR, NGFR, TrkA, ABL, CDK, PI3K, VEGFR, BRAF, MEK, AKT, ALK, BTK, BCKDK, FLT3, JAK2, AURKA, c-MET, DDR, INSR, JNK, IkB, IKK, Lyn, mTOR, PAK, PDK, PTK2/FAK, pyruvate kinases, RAC-a, RIPK, TYK2, SHP, aPKC, NOP, GPC family, μ opioid receptor, δ opioid receptor, UMPK, SphK, PDGFR, and GSK-3 binding moiety;
• B is a target oncogenic protein binding moiety selected from the group consisting of KRAS, RAS, FKPB12F36V, EGFR, HSP90, BTK, MDM2, BRD4, BCR-ABL, NF-kB, LDH-A, p53, GP73, MUC1, MUC16, CD44, GPCR, HMGB1, RIOK1, CHK1, UBE2F, HuR, PTEN, STAT-3, Osteopontin, AKT, DAPK1, Rho, Ubc9, FOXK2, HIC1, HER2, BRAF, BCL-2, CD117, c-KIT, ALK, PI3K, Delta, DNMT1, and SMO;
• L1 and L2 are each a linker;
• and
• E is an electrophilic reactive group and is selected from the group consisting of: