FGFR Degrader

LC-MF-4 is an orally active VHL-recruiting FGFR3 PROTAC degrader and hERG potassium channel inhibitor. LC-MF-4 has an IC₅₀ of 16.6 nM against human FGFR3, exhibits inhibitory activity against hERG potassium channels, suppresses the expression of genes related to mitochondrial biogenesis and ATP synthesis, inhibits cancer cell proliferation, and shows significant antitumor activity in mice. LC-MF-4 can be used in the research of bladder cancer, urothelial carcinoma, FGFR3^Y373C mutant cancers, and FGFR3-TACC3 fusion-positive cancers.

LC-MB12 is an orally active PROTAC compound targets FGFR2 degradation with a DC₅₀ of 11.8 nM. LC-MB12 contains BGJ398 (a FGFR2 inhibitor), PROTAC linker and CRBN.LC-MB12 inhibits FGFR2 signaling in gastric cancer cells and has anti-tumor activity.

BR-cpd7 is an orally active, selective PROTAC degrader targeting FGFR1 and FGFR2, with a DC₅₀ of 2.2 nM against FGFR1. BR-cpd7 reduces FGFR signaling. BR-cpd7 induces cell cycle arrest and selectively blocks the proliferation of FGFR1/FGFR2-dependent tumor cells. BR-cpd7 exhibits significant antitumor efficacy in FGFR1-dependent lung cancer animal models, while achieving complete depletion of FGFR1. BR-cpd7 can be used for cancer-related research.

DGY-09-192 is a PROTAC FGFR1/2 degrader (FGFR1: DC₅₀ = 4.35 nM; FGFR2: DC₅₀ = 70 nM). DGY-09-192 preferentially degrades wild-type FGFR1/2 and multiple FGFR2 fusion proteins (including FGFR2-PHGDH and FGFR2-OPTN). DGY-09-192 suppresses downstream FGFR signaling (reducing phosphorylation of FRS2 Y196 and ERK1/2 T202/Y204) in vitro and vivo. DGY-09-192 can be used for the study of FGFR-driven cancers.

PROTAC FGFR2 degrader 1 (compound N5) is a PROTAC that effectively targets FGFR2 with DC₅₀ of 6.46 nM, the FGFR2 IC₅₀ is 0.08 nM. PROTAC FGFR2 degrader 1 has anti-proliferative activity and highly selective, induces G0/G1 arrest of KATOIII and SNU16 cell cycle and inhibits apoptosis by reducing the activation of p-ERK and p-PLCγ, the downstream proteins of FGFR2. PROTAC FGFR2 degrader 1 potently inhibits the growth of SNU16 xenograft tumors in mouse model.

PROTAC FGFR3 Degrader-1 is a fibroblast growth factor receptor 3 (FGFR3) PROTAC degrader, promotes FGFR3 degradation via the ubiquitin-proteasome pathway, and inhibits the downstream FGFR3/PI3K/AKT signaling pathway. PROTAC FGFR3 Degrader-1 can be used for the research of hepatocellular carcinoma.

PROTAC FGFR1 degrader-1 (compound S2H) is a PROTAC degrader targeting FGFR1, with IC₅₀=26.81 nM and DC₅₀=39.78 nM in KG1a cells. PROTAC FGFR1 degrader-1 is composed of CRBN-type E3 ligase ligand (blue part) Pomalidomide (HY-10984), target protein ligand (red part) FGFR1 ligand-1 (HY-170871), and PROTAC linker (black part) 9-Bromononanoic acid (HY-W007587), in which the E3 ligase ligand and linker form a conjugate E3 Ligase Ligand-linker Conjugate 164 (HY-170870).

LC-MG-10 is a selective molecular glue degrader targeting FGFR2, with a DC₅₀ of 230.2 nM in KATO III cells. LC-MG-10 induces proteasomal degradation of FGFR2 via a covalent molecular glue mechanism. LC-MG-10 inhibits cancer cell proliferation. LC-MG-10 suppresses FGFR2-mediated PI3K/AKT and MAPK/ERK signaling pathways. LC-MG-10 can be used in studies related to gastric cancer.

LC-MG-5 is a selective molecular glue degrader targeting FGFR2, with a DC₅₀ of 231.7 nM in KATO III cells. LC-MG-5 induces proteasomal degradation of FGFR2 in a DCAF16-dependent manner via a covalent molecular glue mechanism. LC-MG-5 inhibits cancer cell proliferation. LC-MG-5 suppresses PI3K/AKT and MAPK/ERK signaling pathways mediated by FGFR2. LC-MG-5 can be used in the research of gastric cancer.

FGFR2 degrader 1 (compound 28E) is a selectively PROTACS degrader of FGFR2, with the DC₅₀ of 0.645 nM. FGFR2 plays an important role in cancer research (Pink: ligand of target protein; (HY-13304) black: linker; blue: ligand of E3 ligase).

CYB-5067 is a FGFR molecular glue degrader with a DC₅₀ of 27 nM against FGFR2. CYB-5067 inhibits FGFR1, FGFR3, FGFR4 and downstream FGFR signaling pathways, induces antiproliferative activity in vitro, and exhibits sustained target protein inhibition in vivo without obvious hook effect. CYB-5067 shows significant tumor growth inhibitory activity in the ETV6-FGFR2 fusion Ba/F3 xenograft model. CYB-5067 can be used for the research of FGFR-driven cancers.