For research use only. Not for therapeutic Use.
Zoligratinib (Debio 1347) is an orally available and selective FGFR inhibitor with IC50s of 9.3, 7.6, and 22 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.
Zoligratinib is well balanced in cellular antiproliferative activity against SNU-16 and stability in human liver microsome. The selectivity of 8 to inhibit FGFR over KDR is suggested to be caused by the difference in the interaction with M535 in FGFR1 and L889 in KDR[1]. The IC50 of Zoligratinib is 29 nM for FGF-dependent proliferation and 780 nM for VEGF-dependent proliferation[2].
Zoligratinib treatment shows a dose-dependent tumor regression (tumor growth inhibition (TGI)=106% at 30 mg/kg and 147% at 100 mg/kg) without apparent body weight loss. Zoligratinib treatment also shows significant in vivo efficacy in xenograft mice models with FGFR genetic alterations, such as KG1 (leukemia, FGFR1OP-FGFR1 fusion), MFE280 (endometrial cancer, FGFR2 S252W mutation), UM-UC-14 (bladder cancer, FGFR3 S249C mutation), and RT112/84 (bladder cancer, FGFR3-TACC3 fusion)[1].
| Catalog Number | I001069 |
| CAS Number | 1265229-25-1 |
| Synonyms | [5-amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone |
| Molecular Formula | C20H16N6O |
| Purity | ≥95% |
| InChI | InChI=1S/C20H16N6O/c1-11-23-16-7-6-13(9-17(16)24-11)26-20(21)14(10-22-26)19(27)18-8-12-4-2-3-5-15(12)25-18/h2-10,25H,21H2,1H3,(H,23,24) |
| InChIKey | BEMNJULZEQTDJY-UHFFFAOYSA-N |
| SMILES | CC1=NC2=C(N1)C=C(C=C2)N3C(=C(C=N3)C(=O)C4=CC5=CC=CC=C5N4)N |
| Reference | [1]. Nakanishi Y, et al. The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitor. Mol Cancer Ther. 2014 Nov;13(11):2547-58. [2]. Nakanishi Y, et al. Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3-BAIAP2L1. Mol Cancer Ther. 2015 Mar;14(3):704-12. [3]. Nakanishi Y, et al. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor. Mol Cancer Ther. 2015 Dec;14(12):2831-9. |
