BCI hydrochloride

BCI is an inhibitor of dual specificity phosphatase 6 (DUSP6) and DUSP1.^1,2 (E/Z)-BCI (0.5-2 ?M) inhibits LPS-induced expression of Dusp6 in a concentration-dependent manner and increases nuclear protein levels of Nrf2 in RAW 264.7 macrophages. It also inhibits LPS-induced increases in the production of IL-1β, IL-6, and reactive oxygen species (ROS) in RAW 264.7 and isolated mouse peritoneal macrophages in an ERK-independent manner. (E/Z)-BCI inhibits proliferation, migration, and invasion of gastric cancer cells in an ERK-dependent manner and induces cell death in part via the DNA damage response pathway.² It reduces tumor growth in a gastric cancer patient-derived xenograft (PDX) mouse model when administered at a dose of 35 mg/kg every seven days and has an additive effect when used in combination with CDDP . The (E) isomer of BCI inhibits DUSP6 and DUSP1 in HeLa cells (IC₅₀s = 12.3 and 11.5 ?M, respectively, for the human recombinant enzymes) and prevents pERK2 dephosphorylation induced by DUSP6 in vitro.³ It is selective for DUSP6 and DUSP1 over DUSP3/VHR, Cdc25B, and PTP1B, for which it has no activity. (E)-BCI induces expansion of the cardiac progenitor cell pool and increases heart size in zebrafish embryos. This product is a mixture of the (E) and (Z) isomers of BCI.²

1.Zhang, F., Tang, B., Zhang, Z., et al.DUSP6 inhibitor (E/Z)-BCI hydrochloride attenuates lipopolysaccharide-induced inflammatory responses in murine macrophage cells via activating the Nrf2 signaling axis and inhibiting the NF-κB pathwayInflammation42(2)672-681(2019) 2.Wu, Q.-N., Liao, Y.-F., Lu, Y.-X., et al.Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistanceCancer Lett.412243-255(2018) 3.Molina, G., Vogt, A., Bakan, A., et al.Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineagesNat. Chem. Biol.5(9)680-687(2009)