GNE-7883 is a pan-TEAD inhibitor that blocks the association of YAP/TAZ with TEAD. GNE-7883 effectively reduces chromatin accessibility at TEAD motifs, inhibits cell proliferation in multiple cell line models, and achieves strong anti-tumor efficacy in vivo. In addition, GNE-7883 effectively overcomes intrinsic and acquired resistance to KRAS (Kirsten rat sarcoma viral oncogene homolog) G12C inhibitors in multiple preclinical models by inhibiting YAP/TAZ activation.
GNE-7883 exhibits strong dose-dependent antiproliferative effects in both OVCAR-8 and NCI-H226 cells, with EC50 values of 115 nM and 333 nM, respectively[3].
GNE-7883 (100 and 250 mg/kg; s.c.; once daily for 4 days) induces tumor growth arrest in NCI-H226 xenograft mice and tumor regression in MSTO-211H xenograft mice[1].
References:
[1]. Hagenbeek TJ, et al. An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance. Nat Cancer. 2023 Jun;4(6):812-828.
[2]. McGee L E. YAP Signaling Promotes Resistance to MEK Inhibition in NF1-Related MPNSTs[M]. Van Andel Research Institute, 2023. [3]. Barry E R, et al. Recent therapeutic approaches to modulate the Hippo pathway in oncology and regenerative medicine[J]. Cells, 2021, 10(10): 2715.