RO3280

Uses

Ro3280 is a Polo-like kinase 1 (PLK1) inhibitor. Ro3280 shows strong antitumor activity in xenograft mouse models, has good selectivity against other kinases and has excellent in vitro cellular potency.

Biological Activity

ro3280 is a selective inhibitor of plk1 with ic50 value of 3 nm [1].polo-like kinase 1 (plk1) is an enzyme and plays an important role in regulating cell cycles as an early trigger for g2/m phase transition. it has been shown that plk1 is over-expressed in a variety of cancer cells and thus is regarded as a promising target for cancer drugs [2].when tested with a panel of acute leukemia cell lines, ro3280 showed inhibitory function on u937, hl 60, nb4, k562, mv4-11, and ccrf with ic50 value of 186 nm, 175 nm, 74 nm, 797 nm, 120 nm, and 162 nm, respectively. it was interesting to notice that all cells (35.49-110.76 nm) were more sensitive to ro3280 compared with aml cells (ic50, 52.80-147.50 nm). further, it was showed that ro3280 treatment decreased cell viability, induced apoptosis and disrupted cell cycle [3]. in h82 (lung cancer), ht-29 (colon cancer), mda-mb-468 (breast cancer), pc3 (prostate cancer), and a375 (cutaneum carcinoma), ro3280 treatment inhibited plk1 with the ic50 was 5 nm, 10 nm, 19 nm, 12 nm, and 70 nm, respectively [1].in nude mice model with ht-29 cells subcutaneous xenograft, administration of ro3280 caused significant anti-tumor activity with 78% reduction at the dose of 40 mg/kg, once a week and then completely regressed tumor when more drug and more frequent [1].

in vivo

target

PLK1

IC 50

PLK1: 0.09 nM (Kd); ALK: 230 nM (Kd); CAMKK1: 1100 nM (Kd); CAMKK2: 87 nM (Kd); DAPK1: 100 nM (Kd); DAPK3: 70 nM (Kd); FER: 53 nM (Kd); GAK: 87 nM (Kd); MYLK: 170 nM (Kd); PTK2: 84 nM (Kd); PTK2B: 130 nM (Kd); RPS6KA6 (KinDom.2): 560 nM (Kd); TTK: 51 nM (Kd)

References

[1]. chen, s., et al., identification of novel, potent and selective inhibitors of polo-like kinase 1. bioorg med chem lett, 2012. 22(2): p. 1247-50.
[2]. czaplinski, s., et al., polo-like kinase 1 inhibition sensitizes neuroblastoma cells for vinca alkaloid-induced apoptosis. oncotarget, 2015.
[3]. wang, n.n., et al., molecular targeting of the oncoprotein plk1 in pediatric acute myeloid leukemia: ro3280, a novel plk1 inhibitor, induces apoptosis in leukemia cells. int j mol sci, 2015. 16(1): p. 1266-92.