PD-166866 is a selective and orally active FGFR1 (fibroblast growth factor receptor 1) tyrosine kinase inhibitor, with an IC₅₀ of 52.4nM[1]. FGFR1 is a transmembrane receptor tyrosine kinase that, upon ligand binding, activates downstream signaling cascades regulating cell proliferation, differentiation, and survival[2]. PD-166866 inhibits FGFR1 tyrosine kinase activity through an ATP-competitive mechanism and is widely used to study FGFR-driven signaling in tumor growth, angiogenesis, and related pathophysiological processes[3].
In vitro, treatment of lymphatic endothelial cells with 1μM PD-166866 for 48h significantly inhibited the proliferation, migration, invasion, and tube formation, reduced the phosphorylation levels of FGFR1, PTEN, and AKT, and decreased CXCL9 secretion[4]. PD-166866 (0.1-50μM; 24h) reduced cell viability, increased membrane damage, induced DNA fragmentation, and accumulated PARP in HeLa cells[5].
In vivo, PD-166866 (0.1 or 0.5mg/day; i.p.; 2 weeks) significantly reduced tumor volume and decreased the number of proliferating cell nuclear antigen (PCNA)-positive cells in SYO-1 xenograft tumors in BALB/c nu/nu mice[6]. Combination of PD-166866 (30mg/kg; every 2 days for 14 days; i.p.) and rapamycin significantly inhibited the growth and progression of T-ALL cells and prolonged the survival time of the Jurkat cell-derived xenograft NCG mice[7].
References:
[1] Panek RL, Lu GH, Dahring TK, et al. In vitro biological characterization and antiangiogenic effects of PD 166866, a selective inhibitor of the FGF-1 receptor tyrosine kinase. J Pharmacol Exp Ther. 1998;286(1):569-577.
[2] Kaur N, Gare SR, Shen J, Raja R, Fonseka O, Liu W. Multi-organ FGF21-FGFR1 signaling in metabolic health and disease. Front Cardiovasc Med. 2022;9:962561.
[3] Calandrella N, Risuleo G, Scarsella G, et al. Reduction of cell proliferation induced by PD166866: an inhibitor of the basic fibroblast growth factor. J Exp Clin Cancer Res. 2007;26(3):405-409.
[4] Kang J, Cheng A, Chen G, Zhu L, Han Z, Xu Q. Tumor Cells-Derived FGF-2 Promotes Lymphangiogenesis as a Prognostic Marker in OSCC. J Oral Pathol Med. 2025;54(8):694-705.
[5] Risuleo G, Ciacciarelli M, Castelli M, Galati G. The synthetic inhibitor of fibroblast growth factor receptor PD166866 controls negatively the growth of tumor cells in culture. J Exp Clin Cancer Res. 2009;28(1):151.
[6] Ishibe T, Nakayama T, Okamoto T, et al. Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy. Clin Cancer Res. 2005;11(7):2702-2712.
[7] Zhang ZJ, Wu QF, Ren AQ, et al. ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming. Acta Pharmacol Sin. 2023;44(11):2282-2295.
PD-166866是一种选择性且具有口服活性的FGFR1（成纤维细胞生长因子受体1）酪氨酸激酶抑制剂，IC50为52.4nM[1]。FGFR1是一种跨膜受体酪氨酸激酶，配体结合后可激活下游信号级联反应，调节细胞增殖、分化和存活[2]。PD-166866通过ATP竞争机制抑制FGFR1酪氨酸激酶活性，广泛用于研究FGFR驱动的肿瘤生长、血管生成及相关病理生理过程中的信号传导[3]。
在体外实验中，用1μM PD-166866处理淋巴管内皮细胞48小时显著抑制了细胞的增殖、迁移、侵袭和管状形成能力，降低了FGFR1、PTEN和AKT的磷酸化水平，并减少了CXCL9的分泌[4]。在HeLa细胞中，PD-166866（0.1-50μM；处理24小时）降低了细胞活性，增加了膜损伤，诱导了DNA片段化，并使PARP蛋白积累[5]。
在体内实验中，PD-166866（0.1或0.5mg/天；腹腔注射；2周）显著减少了SYO-1异种移植瘤在BALB/c nu/nu小鼠中的肿瘤体积，降低了增殖细胞核抗原（PCNA）阳性细胞的数量[6]。PD-166866（30mg/kg；每2天一次；共14天；腹腔注射）与雷帕霉素联合使用，显著抑制了T-ALL细胞的生长和进展，并延长了Jurkat细胞衍生异种移植NCG小鼠的存活时间[7]。