BGJ398 (Infigratinib) is an oral, ATP-competitive pan-FGFR tyrosine kinase inhibitor (FGFR1: IC50 = 0.9nM; FGFR2: IC50 = 1.4nM; FGFR3: IC50 = 1nM; FGFR4: IC50 = 60nM) [1]. BGJ398 targets the fibroblast growth factor receptors FGFR1, FGFR2, FGFR3, and FGFR4, thereby blocking signal transduction mediated by these receptors and inhibiting FGFR-dependent tumor cell proliferation and angiogenesis [2-3]. BGJ398 is primarily used to treat dwarfism in children [4].
In SKOV3ip1 cells, the survival rate of cell in spheroid culture was significantly reduced after BGJ398 (0.3125-5µM; 72h) treatment [5]. In UMUC-14 cells, the combination of paclitaxel and BGJ398 (0-10µM; 72h) can produce a synergistic effect in promoting cell apoptosis [6].
In TMK-1 cells xenograft mice model, treatment with BGJ398 (10mg/kg; po; 20d) significantly inhibited tumor growth [7]. In Snu16R‑derived xenograft mice model, knockdown of BAG3 enhances the anti-tumor effect induced by BGJ398 (30mg/kg; po; 4 weeks) [8].
References:
[1]. Guagnano V, Furet P, Spanka C, et al. Discovery of 3-(2, 6-dichloro-3, 5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase[J]. Journal of medicinal chemistry, 2011, 54(20): 7066-7083.
[2]. Szymczyk J, Sluzalska K D, Materla I, et al. FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance[J]. Cancers, 2021, 13(22): 5796.
[3]. Agrawal S, Maity S, AlRaawi Z, et al. Targeting drugs against fibroblast growth factor (s)-induced cell signaling[J]. Current drug targets, 2021, 22(2): 214-240.
[4]. Högler W, Ward L M. New developments in the management of achondroplasia[J]. Wiener Medizinische Wochenschrift, 2020, 170(5): 104-111.
[5]. Cha H J, Choi J H, Park I C, et al. Selective FGFR inhibitor BGJ398 inhibits phosphorylation of AKT and STAT3 and induces cytotoxicity in sphere-cultured ovarian cancer cells[J]. International Journal of Oncology, 2017, 50(4): 1279-1288.
[6]. Kim S H, Ryu H, Ock C Y, et al. BGJ398, a pan-FGFR inhibitor, overcomes paclitaxel resistance in urothelial carcinoma with FGFR1 overexpression[J]. International journal of molecular sciences, 2018, 19(10): 3164.
[7]. Schmidt K, Moser C, Hellerbrand C, et al. Targeting fibroblast growth factor receptor (FGFR) with BGJ398 in a gastric cancer model[J]. Anticancer Research, 2015, 35(12): 6655-6665.
[8]. Li K, Deng X, Feng G, et al. Knockdown of Bcl-2-associated athanogene-3 can enhance the efficacy of BGJ398 via suppressing migration and inducing apoptosis in gastric cancer[J]. Digestive Diseases and Sciences, 2021, 66(9): 3036-3044.
BGJ398 (Infigratinib)是一种口服的ATP竞争性泛FGFR酪氨酸激酶抑制剂（FGFR1：IC50 = 0.9nM；FGFR2：IC50 = 1.4nM；FGFR3：IC50 = 1nM；FGFR4：IC50 = 60nM） [1]。BGJ398靶向成纤维细胞生长因子受体FGFR1、FGFR2、FGFR3和FGFR4，从而阻断这些受体介导的信号转导，抑制FGFR依赖性的肿瘤细胞增殖和血管生成 [2-3]。BGJ398主要用于治疗儿童侏儒症 [4]。
在SKOV3ip1细胞中，BGJ398（0.3125-5µM；72h）处理后，球状培养细胞的存活率显著降低 [5]。在UMUC-14细胞中，paclitaxel与BGJ398（0-10µM；72h）联合应用可产生促进细胞凋亡的协同作用 [6]。
在TMK-1细胞异种移植小鼠模型中，BGJ398（10mg/kg；po；20d）治疗显著抑制肿瘤生长 [7]。在Snu16R衍生的异种移植小鼠模型中，BAG3的敲低增强了BGJ398（30mg/kg；po；4周）诱导的抗肿瘤作用 [8]。