Abstract
RhoA has been implicated in diverse cellular functions and is a potential cancer therapeutic target. Through virtual screening, we have identified a RhoA inhibitor, DDO-5701. DDO-5701 has an affinity to RhoA at the micromolar level in vitro. By structural modifications, considering the binding activity and synthesis ease of DDO-5701, 17 compounds were designed and synthesized accordingly. Among these compounds, 4 compounds (DDO-5713, DDO-5714, DDO-5715, DDO-5716) exhibited higher RhoA inhibition activities than DDO-5701, while DDO-5716 can effectively reverse the functions of breast cancer cells regulated by RhoA. Thus, the rationally designed small molecule inhibitor of RhoA (DDO-5716) is useful for studying the physiological and pathological roles of Rho GTPase. However, DDO-5701 is an approved drug-proglumide, which makes it and its derived compound DDO-5716 more likely to be well tolerated in humans and could quickly lead to further clinical development.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 56738-56746 |
| Number of pages | 9 |
| Journal | RSC Advances |
| Volume | 6 |
| Issue number | 61 |
| DOIs | |
| State | Published - 2016 |
| Externally published | Yes |
ASJC Scopus subject areas
- General Chemistry
- General Chemical Engineering