AI Article Synopsis
- c-Met and VEGFR-2 are crucial targets in cancer treatment, leading to the design of new dual inhibitors.
- A series of [1,4]dioxino[2,3-f]quinazoline derivatives were created, showing strong inhibition of both targets, particularly compounds 7m and 7k.
- Compound 7k exhibited significant anti-tumor effects in a mouse model for hepatocellular carcinoma, suggesting its potential as a cancer therapy.
Article Abstract
Both c-Met and VEGFR-2 were important targets for cancer therapies. In order to develop reversible and non-covalent c-Met and VEGFR-2 dual inhibitors, a series of [1,4]dioxino[2,3-f]quinazoline derivatives were designed and synthesized. The enzyme assay demonstrated that most target compounds had inhibition potency on both c-Met and VEGFR-2 with IC values in nanomolar range especially compounds 7m and 7k. Based on further cell proliferation assay in vitro, compound 7k showed significantly anti-tumor activity in vivo on a hepatocellular carcinoma (MHCC97H cells) xenograft mouse model. We docked the compound 7m with c-Met and VEGFR-2 kinases, and interpreted the SAR of these analogues. All results indicated that the target compounds were dual inhibitors of c-Met and VEGFR-2 kinases that held promising potential in cancer therapy.
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| http://dx.doi.org/10.1016/j.bioorg.2019.04.010 | DOI Listing |
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