Golvatinib (E7050) is a a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family, as well as c-Kit and Ron, with an IC50 for c-Met of 0.001μM, for Eph members (A6, B2, A8, A7, B4, B1, and A5) between 0.007 and 0.018μM, for Kit of 0.010μM, and for Ron of 0.017μM[1]. Golvatinib directly modulates ABCG2 transporter activity, restoring cellular sensitivity to representative ABCG2 substrates by inhibiting efflux of substrates and increasing intracellular drug accumulation [2]. Golvatinib effectively interferes with the binding of the non-structural protein 1 (Nsp1) of SARS-CoV-2 to the host 40S ribosomal subunit, thereby preventing SARS-CoV-2 infection[3]. Golvatinib has been widely used to reduce tumor angiogenesis and inhibit the growth of various tumor cells[4].
In vitro, Golvatinib treatment for 72 hours significantly inhibited the viability of A549, HeLa, and MCF-7 cells, with IC50 values of 6.89µM, 4.14µM and 20.61µM, respectively[5]. Treatment of mouse macrophages with 0.3µM Golvatinib for 24 hours inhibited the upregulation of Tie2 expression induced by hypoxia and angiopoietin-2[6]. 5µM of Golvatinib incubation for 48 hours inhibited the proliferation and migration of A375 cells and aggravated cell senescence[7].
In vivo, oral administration of Golvatinib at a dose of 50mg/kg daily for 12 days significantly suppressed tumor growth in the A375 xenograft mouse model[7]. Daily oral administration of Golvatinib at a dose of 100mg/kg for 14 consecutive days markedly restrained systemic metastasis of small-cell lung cancer cells in SCID mice[8].
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[2] Chen X Y, Cao L Q, Chen X, et al. Golvatinib (E7050) restores chemosensitivity in multidrug-resistant cancer cells by inhibiting ABCG2 transporter[J]. Pathology-Research and Practice, 2026: 156663.
[3] Shen M, Ding P, Luan G, et al. The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients[J]. Frontiers in Cellular and Infection Microbiology, 2023, 13: 1141274.
[4] Nakagawa T, Matsushima T, Kawano S, et al. Lenvatinib in combination with golvatinib overcomes hepatocyte growth factor pathway‐induced resistance to vascular endothelial growth factor receptor inhibitor[J]. Cancer Science, 2014, 105(6): 723-730.
[5] Xiong H, Zhang J, Zhang Q, et al. Design, synthesis and biological evaluation of 4-(pyridin-4-yloxy) benzamide derivatives bearing a 5-methylpyridazin-3 (2H)-one fragment[J]. Bioorganic & Medicinal Chemistry Letters, 2020, 30(9): 127076.
[6] Nakazawa Y, Kawano S, Matsui J, et al. Multitargeting strategy using lenvatinib and golvatinib: Maximizing anti‐angiogenesis activity in a preclinical cancer model[J]. Cancer science, 2015, 106(2): 201-207.
[7] Qiu Z, Sun C, Wang J, et al. USP10 stabilizes FOXM1 through KAT5-mediated acetylation to suppress cell senescence and promote melanoma malignant progression[J]. International Journal of Biological Sciences, 2026, 22(14): 8029.
[8] Taniguchi H, Yamada T, Takeuchi S, et al. Impact of MET inhibition on small‐cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway[J]. Cancer Science, 2017, 108(7): 1378-1385.