RET Degrader

RET ligand-5 is a PROTAC target protein ligand that can be used for synthesis of PROTACs, such as PROTAC RET Degrader 1 (HY-178964). PROTAC RET Degrader 1 is a potent RET PROTAC degrader with anti-tumor activity.

QZ2135 (compound 20) is a RET-targeted PROTAC degrader with in vivo antitumor properties in a Ba/F3-KIF5B-RET-G810C xenograft mouse model. The degradation activities of QZ2135 targeting KIF5B-RET have DC₅₀ values of 4.7 nM (WT), 17.2 nM (V804M), and 73.8 nM (G810C), respectively. QZ2135 is composed of a target protein ligand (red part) RET ligand-3 (HY-170853), an E3 ligase ligand (blue part) Lenalidomide-F (HY-W039233), and a PROTAC Linker (black part) 7-Iodohept-1-yne (HY-W587352), in which the target protein ligand + linker form a conjugate RET Ligand-Linker Conjugate-1 (HY-170854).

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.

YW-N-7 (TFA) is a PROTAC that targets both the inhibition and degradation of RET kinase, with a DC₅₀ of 88 nM. YW-N-7 (TFA) exhibits antitumor activity in a KIF5B-RET-driven xenograft mouse tumor model and can be used in the area of cancer (Structure: red part represents the target protein ligand: HY-170856; blue part represents the E3 ligase ligand: HY-1708557; black part represents the linker; E3 ligase ligand + linker: HY-170858).

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.

RET ligand-3 is the ligand for targeting RET PROTAC QZ2135 (HY-170852).

PROTAC RET Degrader 2 is a RET degrader with a target IC₅₀ of 0.36 nM. PROTAC RET Degrader 2 is mainly composed of RET-IN-34 (HY-183729) and Thalidomide (HY-14658). PROTAC RET Degrader 2 mediates RET degradation via the ubiquitin-proteasome system. PROTAC RET Degrader 2 induces apoptosis, inhibits colony-forming ability, and exhibits antiproliferative activity in cancer cells. PROTAC RET Degrader 2 suppresses tumor growth in xenograft models. PROTAC RET Degrader 2 can be used in research related to medullary thyroid carcinoma, papillary thyroid carcinoma, and RET fusion-positive lung adenocarcinoma.

PROTAC RET Degrader 1 (Compound 20) is an orally active and blood-brain barrier-crossing RET PROTAC degrader with DC₅₀ values for RET (WT), RET (G810S), RET (G810C), and RET (G810R) of 1.7, 3, 12, and 21 nM, respectively. PROTAC RET Degrader 1 exhibits potent anti-proliferative activity in cancer cell lines carrying oncogenic RET fusions (such as KIF5B-RET, CCDC6-RET) or mutations (such as RET (C634W)). PROTAC RET Degrader 1 shows significant anti-tumor activity in human tumor xenograft (PDX) mouse models. PROTAC RET Degrader 1 can be used for the study of RET-positive cancers Pink: RET ligand (HY-179308); Blue: CRBN ligand (HY-179307); Black: Linker).

PROTAC HyTTD Degrader-1 (Compound B2) is a hydrophobic tag tethered degrader (HyTTD) targeting RET, as well as a degrader of the CCDC6-RET fusion protein. PROTAC HyTTD Degrader-1 induces the degradation of the CCDC6-RET fusion protein via the ubiquitin-proteasome pathway. PROTAC HyTTD Degrader-1 is applicable to the research of RET-driven cancers.

RD-23 is an orally active and selective RET PROTAC degrader, with DC₅₀ values of 5.6 nM and 11.7 nM against RET^WT and RET^G810C mutants, respectively. RD-23 inhibits purified RET kinase activity with an IC₅₀ of 0.371 nM. RD-23 suppresses the activation of downstream Shc signaling and induces apoptosis. RD-23 can be used for the research of RET-related cancers.