LXH-3-71

LXH-3-71 is a PHGDH degrader. LXH-3-71 acts as a molecular glue to enhance the interaction of the PHGDH-DDB1-CRL E3 ligase complex, triggering ubiquitination and proteasomal degradation of PHGDH. LXH-3-71 regulates the stemness of colorectal cancer cells and inhibits tumor proliferation and colony formation. LXH-3-71 can be used in the research of colorectal cancer ^[1].

In Vivo, LXH-3-71 (1-3 mg/kg; i.p.; once daily; for 17 consecutive days) dose-dependently inhibits the growth of subcutaneous colorectal tumors in BALB/c nude mice^[1]. LXH-3-71 (1-3 mg/kg; i.p.; once daily; for 28 consecutive days) significantly reduces lung metastatic burden in a BALB/c nude mouse model of colorectal cancer metastasis^[1].

In Vitro, LXH-3-71 (72 h) inhibits the proliferation of HCT-15, HCT-116, LoVo, SW480, CT26 and RKO colorectal cancer cells in vitro^[1]. LXH-3-71 (2.5-5 μM) inhibits colony formation of HCT-116 and SW480 colorectal cancer cells^[1]. LXH-3-71 (2.5-5 μM; 3 days) reduces the tumorsphere-forming ability of HCT-116 and SW480 colorectal cancer cells in a dose-dependent manner^[1]. LXH-3-71 (0.5-8 μM; 0-24 h) induces dose- and time-dependent degradation of PHGDH protein via the proteasomal pathway in HCT-116 and HCT-15 colorectal cancer cells^[1].

References:
[1]. Huang Z, et al. Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH. Acta Pharm Sin B. 2024;14(9):4001-4013.