	US 12,404,348 B2
	Bifunctional chimeric molecules for labeling of kinases with target binding moieties and methods of use thereof
Amit Choudhary, Boston, MA (US); Vika Anokhina, Cambridge, MA (US); Santosh Chaudhary, Cambridge, MA (US); Prashant Singh, Cambridge, MA (US); Sameek Singh, Cambridge, MA (US); Veronika Shoba, Cambridge, MA (US); Uttam Dhawa, Cambridge, MA (US); Ashley Modell, Cambridge, MA (US); and Praveen Tiwari, Boston, MA (US)
Assigned to The Brigham and Women's Hospital, Inc., Boston, MA (US); and The Broad Institute, Inc., Cambridge, MA (US)
Filed by The Brigham and Women's Hospital, Inc., Boston, MA (US); and The Broad Institute, Inc., Cambridge, MA (US)
Filed on Nov. 18, 2022, as Appl. No. 18/057,127.
Claims priority of provisional application 63/281,538, filed on Nov. 19, 2021.
Prior Publication US 2023/0192904 A1, Jun. 22, 2023
Int. Cl. A61K 49/00 (2006.01); C07K 16/40 (2006.01); C07K 19/00 (2006.01)

CPC C07K 19/00 (2013.01) [A61K 49/0017 (2013.01); C07K 16/40 (2013.01)]

27 Claims

1. 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, FKPB^12F36V, 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: