Retinoblastoma protein (Rb), a tumor suppressor protein, is dysfunctional in several major cancers. Specifically, one of the functions of Rb is to prevent excessive cell growth by inhibiting cell cycle progression until cells are ready to divide. Besides, many studies have shown that all three Rb family pocket proteins (PRb, p107, and p130) are hyperphosphorylated in human melanoma cells. Moreover, Rb plays an important role in the regulation of mammalian cell proliferation through the interaction with the E2F transcription factor family. Furthermore, signal kinase Raf-1 can physically bind to Rb and phosphorylate Rb at the early stage of the cell cycle. Thus it promotes the over phosphorylation of CDK and ultimately inactivating CDK. Furthermore, these results indicate that blocking the binding of Raf-1 with Rb can keep Rb in a low phosphorylated form and exert its anti-cancer effect completely. RRD-251 is an inhibitor of retinoblastoma tumor suppressor protein (Rb)-Raf-1 interaction.

RRD-251 is an inhibitor of Rb-Raf-1 interaction.

But, how does RRD-251 protect against cancer cells via RRD-251? At first, RRD-251 with 10-50 μM of 24 hours inhibits melanoma growth in-vitro. Nonetheless, RRD-251 inhibits Rb-Raf-1 interaction and Rb phosphorylation in non-small cell lung cancer cells. Nonetheless, RRD-251 induces apoptosis and cell cycle arrest. Particularly, RRD-251 alters the expression of cell cycle and apoptosis regulatory protein.

In addition, RRD-251 with 50 mg/kg/qod of i.p. for 14 days has anti-cancer activities in vivo on melanomas. Obviously, RRD-251 inhibits the growth of SK-ME-28 xenograft in nude mice.

All in all, RRD-251 is an inhibitor of Rb-Raf-1 interaction, with potent anti-proliferative, anti-angiogenic, and anti-tumor activities.


Sandeep Singh, et al. Mol Cancer Ther. 2010 Dec; 9(12): 3330–3341.