BAY-8002 is a potent, selective, orally active inhibitor of monocarboxylate transporter 1 (MCT1), with an IC50 of 85nM[1]. BAY-8002 targets MCT1 to regulate the MCT1-mTOR signaling pathway, thereby increasing autophagy and influencing the formation of mineralized nodules and the expression of osteogenic-related proteins[2]. BAY-8002 has been widely used to regulate the expression of SLC16A1 to alter the response of prostate cancer cells to afatinib[3].
In vitro, BAY-8002 treatment (10µM) for 5 days significantly inhibited lipid accumulation in immortalized mouse E12.5 hepatic progenitor (iHPx) cells, and reduced the expression of genes involved in the synthesis and regulation of triglycerides and fatty acids[4]. Treatment with 1µM BAY-8002 for 1 hour increased the nuclear translocation of the DNA-PK catalytic subunit (DNA-PKcs), enhanced lactate flux, and decreased the transduction efficiency of lentivirus in HeLa cells[5]. 100nM of BAY-8002 incubated for 24 hours, which restrained the migration of MCF-7 cells stimulated by matrix cell-conditioned medium (CM)[6]. 75µM of BAY-8002 pretreatment for 1 hour reduced the extracellular lactate level and inhibited the expression of IL-9 in human T helper 9 (TH9) cells[7].
In vivo, BAY-8002 treatment via oral administration at a dose of 160mg/kg twice daily for 28 days significantly suppressed tumor growth in Raji Burkitt lymphoma tumor-bearing mice, without affecting the body weight[1].
References:[1] Quanz M, Bender E, Kopitz C, et al. Preclinical efficacy of the novel monocarboxylate transporter 1 inhibitor BAY-8002 and associated markers of resistance[J]. Molecular Cancer Therapeutics, 2018, 17(11): 2285-2296.
[2] Luo Y, Gou H, Chen X, et al. Lactate inhibits osteogenic differentiation of human periodontal ligament stem cells via autophagy through the MCT1-mTOR signaling pathway[J]. Bone, 2022, 162: 116444.
[3] Matheux A, Gassiot M, Fromont G, et al. PXR modulates the prostate cancer cell response to afatinib by regulating the expression of the monocarboxylate transporter SLC16A1[J]. Cancers, 2021, 13(14): 3635.
[4] Gou Y, Li A, Dong X, et al. Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease[J]. Genes & Diseases, 2025, 12(4): 101554.
[5] Wagner W, Sobierajska K, Kania K D, et al. Lactate suppresses retroviral transduction in cervical epithelial cells through DNA-PKcs modulation[J]. International Journal of Molecular Sciences, 2021, 22(24): 13194.
[6] Vera M J, Ponce I, Almarza C, et al. CCL2 and lactate from chemotherapeutics-treated fibroblasts drive malignant traits by metabolic rewiring in low-migrating breast cancer cell lines[J]. Antioxidants, 2024, 13(7): 801.
[7] Bertschi N L, Steck O, Luther F, et al. PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis[J]. Nature Communications, 2023, 14(1): 2471.