Cell lines

AN3CA, MFE296, MFE280, SNGM and HEC1A cells

Preparation method

The solubility of this compound in DMSO is

Reaction Conditions

0.5 μM, 72 hours

Applications

Exposure of AN3CA, MFE296, and MFE280 cells to the inhibitor led to a significant increase in the fraction of cells in G0–G1 arrest and to a significant increase in the fraction of cells undergoing apoptosis, when compared with untreated controls. In contrast, NVP-BGJ398 treatment did not alter the fractions of cells in G0–G1 arrest in the FGFR2 wild-type endometrial cancer cell lines SNGM or HEC1A in vitro. Moreover, NVP-BGJ398 treatment had no effect on apoptosis in the FGFR2 wild-type endometrial cancer cell line HEC1A.

Animal models

Nude mice bearing AN3CA, MFE296, SNGM or HEC1A xenografts

Dosage form

Oral administration, 30 or 50 mg/kg, daily

Applications

NVP-BGJ398 significantly delayed the growth of FGFR2-mutated endometrial cancer xenograft tumors. In contrast, NVP-BGJ398 had no in vivo inhibitory effects in the long-term study using the FGFR2 wild-type endometrial cancer cell line SNGM, but surprisingly did show in vivo activity in HEC1A cells by delaying tumor growth in these cells.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

NVP-BGJ398 is a potent, selective, and orally bioavailable inhibitor of the FGFR tyrosine kinases. NVP-BGJ398 is a small molecular with the formula of C₂₆H₃₁Cl₂N₇O₃and Molecular Weight of 560. The fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, and FGFR4, encompasses the receptors for 18 different FGF ligands. These ligand–receptor combinations regulate a broad spectrum of signaling during development and in normal growth control. BGJ398 inhibits the cell proliferation and induces apoptosis in cancer cells and suppresses tumor growth in xenograft model.

References:
1. Fibroblast Growth Factor Receptors as Novel Therapeutic Targets in SNF5-Deleted Malignant Rhabdoid Tumors. S Wöhrle, A Weiss, M Ito, A Kauffmann, M Murakami. PLOS ONE. 2013
2. Rescue screens with secreted proteins reveal compensatory potential of receptor tyrosine kinases in driving cancer growth. F Harbinski, VJ Craig, S Sanghavi, D Jeffery, L Liu. Cancer Discovery, 2012