Erdafitinib is an orally available, selective tyrosine kinase inhibitor of the entire FGFR family (FGFR1: IC50 = 1.2nM; FGFR2: IC50 = 2.5nM; FGFR3: IC50 = 3.0nM; FGFR4: IC50 = 5.7nM) [1]. Erdafitinib inhibits the proliferation and survival of cells with abnormal FGFR genes (such as FGFR3 or FGFR2 variants) by blocking phosphorylation and downstream signaling pathways, thereby inducing apoptosis [2-3]. Erdafitinib is primarily used to treat advanced or metastatic urothelial carcinoma harboring FGFR2/3 genetic abnormalities [4].
In HEK293 ABCB1 overexpressing cells, Erdafitinib (0.06-0.6μM; 2 h) enhances the sensitivity of cells to chemotherapeutic drugs [5]. In BV2 microglial cells, Erdafitinib (0.1-20μM; 24h) pretreatment decreases LPS-mediated proinflammatory cytokine expression through NLRP3 [6]. In MDA-MB-231 cells, Erdafitinib (0-100μM; 24h) inhibited the growth of cells in a dose-dependent manner [7].
In A549 cells xenograft tumor mouse model, Erdafitinib (10mg/kg; ip; 21d) suppresses tumor growth, accompanied by decreased CDK2 expression [8]. In SRM KO MGH-U3 cells xenograft tumor mouse model, combination of SRM deletion and Erdafitinib (5mg/kg, 15mg/kg; po; 4 weeks) targeted therapy elicited a complete inhibition of tumor growth [9].
References:
[1]. Perera T P S, Jovcheva E, Mevellec L, et al. Discovery and pharmacological characterization of JNJ-42756493 (Erdafitinib), a functionally selective small-molecule FGFR family inhibitor[J]. Molecular cancer therapeutics, 2017, 16(6): 1010-1020.
[2]. Haura E B, Hicks J K, Boyle T A. Erdafitinib overcomes FGFR3-TACC3–mediated resistance to osimertinib[J]. Journal of Thoracic Oncology, 2020, 15(9): e154-e156.
[3]. Kaur J, Singh A, Shah M, et al. Erdafitinib for tumors with FGFR3 mutation: A promising targeted therapy[J]. Cancer Research, Statistics, and Treatment, 2023, 6(2): 288-295.
[4]. Guercio B J, Sarfaty M, Teo M Y, et al. Clinical and genomic landscape of FGFR3-altered urothelial carcinoma and treatment outcomes with erdafitinib: a real-world experience[J]. Clinical Cancer Research, 2023, 29(22): 4586-4595.
[5]. Feng W, Zhang M, Wu Z X, et al. Erdafitinib antagonizes ABCB1-mediated multidrug resistance in cancer cells[J]. Frontiers in oncology, 2020, 10: 955.
[6]. Lee H, Kim S H, Jung T M, et al. Erdafitinib diminishes LPS-mediated neuroinflammatory responses through NLRP3 in wild-type mice[J]. Frontiers in Pharmacology, 2025, 16: 1572604.
[7]. Luo Q, Zhang L, Hao Y, et al. Erdafitinib inhibits the tumorigenicity of MDA-MB-231 triple-negative breast cancer cells by inducing TRIM25/ubiquitin-dependent degradation of FGFR4[J]. Breast Cancer Research, 2025, 27(1): 128.
[8]. Meng X, Zhu X, Ji J, et al. Erdafitinib inhibits tumorigenesis of human lung adenocarcinoma A549 by inducing S-phase cell-cycle arrest as a CDK2 inhibitor[J]. Molecules, 2022, 27(19): 6733.
[9]. Yu Y, Gao X, Zhao H, et al. A Genome-Wide Synthetic Lethal Screen Identifies Spermidine Synthase as a Target to Enhance Erdafitinib Efficacy in FGFR-Mutant Bladder Cancer[J]. Cancer Research, 2025, 85(12): 2288-2301.
Erdafitinib是一种口服的选择性酪氨酸激酶抑制剂，抑制FGFR家族（FGFR1：IC50 = 1.2nM；FGFR2：IC50 = 2.5nM；FGFR3：IC50 = 3.0nM；FGFR4：IC50 = 5.7nM） [1]。Erdafitinib通过阻断FGFR基因异常（例如FGFR3或FGFR2变体）的磷酸化和下游信号通路，抑制其增殖和存活，从而诱导细胞凋亡 [2-3]。Erdafitinib主要用于治疗伴有FGFR2/3基因异常的晚期或转移性尿路上皮癌 [4]。
在HEK293 ABCB1过表达细胞中，Erdafitinib（0.06-0.6μM；2h）增强细胞对化疗药物的敏感性 [5]。在BV2小胶质细胞中，Erdafitinib（0.1-20μM；24h）预处理可通过NLRP3降低LPS介导的促炎细胞因子表达 [6]。在MDA-MB-231细胞中，Erdafitinib（0-100μM；24h）以剂量依赖性方式抑制细胞的生长 [7]。
在A549细胞异种移植瘤小鼠模型中，Erdafitinib（10mg/kg；ip；21d）可抑制肿瘤生长，并伴随CDK2表达降低 [8]。在SRM KO MGH-U3细胞异种移植肿瘤小鼠模型中，SRM缺失和Erdafitinib（5mg/kg，15mg/kg；po；4周）靶向治疗相结合，可完全抑制肿瘤生长 [9]。