Bafetinib is a dual Bcr-Abl/Lyn tyrosine kinase inhibitor. Bafetinib inhibits Bcr-Abl autophosphorylation and enhances pro-apoptotic protein activity. Bafetinib can be used in research related to chronic myeloid leukemia, chronic lymphocytic leukemia, prostate cancer, and brain tumors[1-4].
In vitro, HEK-293 T cells (stably expressing human ACE2 and TMPRSS2) infected with SARS-CoV-2 Wuhan strain (MOI=0.5i.u./cell) were treated with Bafetinib (0.09, 0.9, and 9μM) for 16-18 hours. Bafetinib significantly inhibited the number of virus-infected cells and suppressed virus-induced syncytium formation[5]. ABCB1-overexpressing SW620/Ad300 and HEK/ABCB1 cells, as well as ABCG2-overexpressing NCI-H460/MX20 and HEK/ABCG2-R482 cells, were pretreated with Bafetinib (1-3 μM) for 1 hour, followed by a 2-hour [³H]-paclitaxel or [³H]-mitoxantrone accumulation assay. Bafetinib significantly increased intracellular drug accumulation and inhibited drug efflux[6].
In vivo, Balb/c mice inoculated with CT26 cells were administered Bafetinib (30mg/kg; once daily) by gavage for 10 days. Bafetinib significantly inhibited tumor growth and markedly suppressed PD-L1 expression[7]. In pain behavior experiments, C57BL/6 mice were administered Bafetinib (10mg/kg; single treatment) by gavage 30 minutes before the test. Bafetinib significantly inhibited PAR2-induced mechanical hyperalgesia[8].
References:
[1] Santos FP, Kantarjian H, Cortes J, et al. Bafetinib, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia. Curr Opin Investig Drugs. 2010 Dec;11(12):1450-65.
[2] Liu D, Jin X, Zeng Y, et al. Bafetinib enhances anti-tumor immunity by activating the NLRP3 inflammasome in macrophage. Autophagy. 2026 Apr 12:1-19.
[3] Kuroda J, Kimura S, Strasser A, et al. Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. Cell Death Differ. 2007 Sep;14(9):1667-77.
[4] Milara J, Martinez-Losa M, Sanz C, et al. Bafetinib inhibits functional responses of human eosinophils in vitro. Eur J Pharmacol. 2013 Sep 5;715(1-3):172-80.
[5] Serra A, Fratello M, Federico A, et al. Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation. Brief Bioinform. 2022 Jan 17;23(1):bbab507.
[6] Zhang YK, Zhang GN, Wang YJ, et al. Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters. Sci Rep. 2016 May 9;6:25694.
[7] Chen X, Du Q, Guo H, et al. Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer. Front Pharmacol. 2022 Jun 2;13:897747.
[8] Grace MS, Lieu T, Darby B, et al. The tyrosine kinase inhibitor bafetinib inhibits PAR2-induced activation of TRPV4 channels in vitro and pain in vivo. Br J Pharmacol. 2014 Aug;171(16):3881-94.
Bafetinib是一种双重Bcr-Abl/Lyn酪氨酸激酶抑制剂。Bafetinib可抑制Bcr-Abl自身磷酸化，增强促凋亡蛋白活性。Bafetinib可用于慢性髓性白血病、慢性淋巴细胞白血病、前列腺癌和脑肿瘤的相关研究[1-4]。
在体外，Bafetinib（0.09、0.9和9μM）处理感染SARS-CoV-2 Wuhan株（MOI=0.5i.u./cell）的HEK-293 T（稳定表达人ACE2和TMPRSS2）细胞16-18小时。Bafetinib显著抑制了病毒感染细胞数量，抑制了病毒诱导的合胞体形成[5]。Bafetinib（1-3μM）预处理ABCB1过表达的SW620/Ad300和HEK/ABCB1细胞以及ABCG2过表达的NCI-H460/MX20和HEK/ABCG2-R482细胞1小时，随后进行2小时[3H]-紫杉醇或[3H]-米托蒽醌积累实验。Bafetinib显著增加了细胞内药物积累，抑制了药物外排[6]。
在体内，Bafetinib（30mg/kg；每日一次）灌胃于接种了CT26细胞的Balb/c小鼠10天。Bafetinib显著抑制了肿瘤生长，同时显著抑制了PD-L1的表达[7]。在疼痛行为实验前30分钟，Bafetinib（10mg/kg；单次处理）灌胃于C57BL/6小鼠。Bafetinib显著抑制了PAR2诱导的机械痛觉过敏[8]。