TrkA Degrader

CG428 is a potent and selective CRBN-dependent tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 TPM3-TRKA fusion protein in KM12 colorectal carcinoma cells (DC₅₀ = 0.36 nM) and inhibits downstream PLCγ1 phosphorylation (IC₅₀ = 0.33 nM). CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively). CG428 can be used for the research of colorectal carcinoma.

ZW-18-116 (compound 9) is a dual-target PROTAC degrader for the oncoproteins TRKA and RET. ZW-18-116 induces the degradation of oncoproteins TRKA and RET by recruiting the CRBN E3 ligase. ZW-18-116 exhibits potent anti-proliferative activity in various cancer cell lines harboring RET or TRKA fusions. ZW-18-116 can be used for RET or TRKA-derived cancer research, such as thyroid, lung, and colon cancers.

ZW-6-052 (compound 20), the derivative of ZW-18-116 (HY-180550), is a dual-target PROTAC degrader for the oncoproteins TRKA and RET. ZW-6-052 induces degradation of TMP3-TRKA in KM12 mouse xenograft models. ZW-6-052 can be used for RET or TRKA-derived cancer research, such as thyroid, lung, and colon cancers.