RRD-251 is an Rb-Raf-1 interaction inhibitor that induces apoptosis in metastatic melanoma cells and synergizes with dacarbazine[1].

RRD-251 (10-50 μM; 24 hours) inhibits melanoma growth in-vitro [1]. RRD-251 (50 μM; 2 hours) inhibits Rb-Raf-1 interaction and Rb phosphorylation in non-small cell lung cancer cells [1]. RRD-251 induces apoptosis (50 μM; 18 hours) and cell cycle arrest (20-50 μM; 4 hours) [1]. RRD-251 alters the expression of cell cycle and apoptosis regulatory protein [1]. Cell Proliferation Assay [1] Cell Line: SK-MEL-28 cells, SK-MEL-5 cells, SK-MEL-2 cells Concentration: 10 μM, 20 μM, 50 μM Incubation Time: 24 hours Result: Inhibited melanoma growth in-vitro. Western Blot Analysis [1] Cell Line: SK-MEL-28 cells, SK-MEL-5 cells, SK-MEL-2 cells Concentration: 50 μM Incubation Time: 2 hours Result: Showed the depletion of phosphorylated-Rb in RRD-251 treated cells. Apoptosis Analysis [1] Cell Line: SK-MEL-28 cells, SK-MEL-5 cells, SK-MEL-2 cells Concentration: 50 μM Incubation Time: 18 hours Result: Induced apoptosis. Cell Cycle Analysis [1] Cell Line: SK-MEL-28 cells, SK-MEL-5 cells Concentration: 20 μM, 50 μM Incubation Time: 4 hours Result: Resulted in a dose dependent inhibition of cell cycle progression in SK-MEL-28 and SK-MEL-5 cells, respectively.

RRD-251 (50 mg/kg; i.p.; q.o.d; for 14 days) has anti-cancer activities in vivo on melanomas [1]. Animal Model: 8-wk-old female athymic nude mice, with SK-ME-28 xenograft [1] Dosage: 50 mg/kg Administration: Intraperitoneal administration, qod, for 14 days Result: Inhibits the growth of SK-ME-28 xenograft in nude mice.