Erdafitinib (Balversa™) is an innovative drug developed by Janssen Pharmaceutical Companies. It is an orally administered pan-fibroblast growth factor receptor (FGFR) inhibitor. Erdafitinib is effective in treating cancers that have FGFR amplifications, mutations, or fusions. Currently, it is approved for patients with urothelial cancer whose tumors contain FGFR2 or FGFR3 mutations or fusions. Beyond urothelial cancer, researchers are exploring its potential for treating other types of cancer, including breast, liver, lung, prostate, and esophageal cancers.
Note: MCE can provide Erdafitinib for research use only. We do not sell to patients.
Erdafitinib is a potent and orally available FGFR family inhibitor
Erdafitinib is a strong inhibitor of the FGFR family. It targets FGFR1, FGFR2, FGFR3, and FGFR4 with IC50 values of 1.2, 2.5, 3.0, and 5.7 nM, respectively. This means that it effectively inhibits these receptors even at low concentrations. In contrast, Erdafitinib is less effective against the related VEGFR2 kinase, which has an IC50 value of 36.8 nM. Additionally, Erdafitinib binds to FGFR1, FGFR3, FGFR4, and FGFR2 with Kd values of 0.24, 1.1, 1.4, and 2.2 nM, respectively. The Kd value for VEGFR2 is higher at 6.6 nM. Erdafitinib also reduces the proliferation of FGFR-expressing cells, with IC50 values of 22.1, 13.2, and 25 nM for FGFR1, FGFR3, and FGFR4, respectively.
Study of Erdafitinib’s Effects on Lung Adenocarcinoma
Researchers recently studied the effects of Erdafitinib on lung adenocarcinoma (LADC) using both in vitro and in vivo models. They used human lung adenocarcinoma A549 cells. Initial experiments showed that FGFR1 was highly expressed in these cells and that Erdafitinib treatment down-regulated FGFR1.
Further analysis revealed that Erdafitinib affected A549 cell viability by inducing S-phase cell-cycle arrest. The study identified CDK2 as a key regulatory target of Erdafitinib. When researchers overexpressed CDK2, they found that it reduced the effects of Erdafitinib on cell-cycle arrest and apoptosis. Additional tests showed that CDK2 influenced the transcriptional activity and expression of E2F1, which in turn affected CDK1 expression. This indicated that Erdafitinib regulates E2F1-CDK1 signaling by impacting CDK2 levels (Figure).
To confirm the drug’s in vivo effects, researchers established an A549 xenograft mouse model. They injected nude mice with either a vehicle or Erdafitinib at 10 mg/kg/day for 21 days. Erdafitinib significantly inhibited tumor growth and reduced tumor volume. Histological analysis of resected tumor tissues showed morphological changes, including signs of cell necrosis and inflammation. Erdafitinib treatment also decreased Ki67-positive cells, indicating reduced cell proliferation, and increased TUNEL-positive cells, showing enhanced apoptosis. Additionally, CDK2 expression was reduced in the treated tumors.
In conclusion, Erdafitinib is a promising selective pan-FGFR inhibitor. Its effectiveness in treating various cancers, especially lung adenocarcinoma, highlights its potential in cancer research and therapy.
Refernces
[1] Perera TPS, et al. Mol Cancer Ther. 2017 Jun;16(6):1010-1020.
