BI-853520

BI 853520 (IN-10018) is an orally active and potent focal adhesion kinase (FAK) inhibitor (recombinant FAK IC50=1 nM). BI 853520 shows anti-proliferative activity against cancer cells[1][2].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FAK

BI 853520 (0-3 μM; 2 h) inhibits cancer cells growth[2]. BI 853520 (0-30 μM; 4-6 d) represses tumor cell proliferation and invasion only in 3D culture[1]. BI 853520 (0-10 μM; 24 h) represses Y397-FAK autophosphorylation[1]. BI 853520 (0.1 μM; 96 h) shows a fast and potent inhibition of FAK in this highly metastatic murine breast cancer cell line[1]. Cell Viability Assay[2] Cell Line: PC-3 cells Concentration: 0-3 μM Incubation Time: 2 hours Result: Resulted in a concentration-dependent reduction of the signal with a median EC50 value of 1 nM. Cell Proliferation Assay[1] Cell Line: 4T1, Py2T, and Py2T-LT cells Concentration: 0-30 μM Incubation Time: 4-6 days Result: Indicated that the specific inhibition of cell proliferation and invasion at low doses is functional only in three-dimensional cell culture conditions, whereas cells cultured on plastic only respond to BI 853520 at very high, toxic doses. Western Blot Analysis[1] Cell Line: 4T1, Py2T, and Py2T-LT cells Concentration: 0-10 μM Incubation Time: 24 hours Result: Reduced Y397-FAK autophosphorylation in all cell types. Western Blot Analysis[1] Cell Line: 4T1, Py2T, and Py2T-LT cells Concentration: 0.1 μM Incubation Time: 96 hours Result: Decreased Y397-FAK autophosphorylation following 0.1 µM BI 853520 treatment occurred within 10 min and was substantially reduced at least for the following 48 h.

BI 853520 (oral gavage; 50 mg/kg; once daily; 0-8 weeks) treatment significantly suppresses primary tumor growth of all three cell lines in vivo[1]. Animal Model: FVB/N, Balb/c, or immunodeficient nude (nu/nu) mice transplanted with Py2T, 4T1, or MTflECad cells, respectively[1] Dosage: 50 mg/kg Administration: Oral gavage; 50 mg/kg; once daily; 0-8 weeks Result: Decreased tumor volume significantly over time.

[1]. Stefanie Tiede, et al. The FAK inhibitor BI 853520 exerts anti-tumor effects in breast cancer. Oncogenesis. 2018 Sep 20;7(9):73.

[2]. Ulrich A Hirt, et al. Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype. Oncogenesis. 2018 Feb 23;7(2):21.