Ro3280

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].

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.

Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells.[Pubmed:25574601]

Int J Mol Sci. 2015 Jan 7;16(1):1266-92.

Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. Ro3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 +/- 110.28 vs. 6.36 +/- 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of Ro3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of Ro3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. Ro3280 induced apoptosis and cell cycle disorder in leukemia cells. Ro3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of Ro3280 for AML therapy; however, the underlying mechanisms remain to be determined.

Ro3280 is a potent, highly selective inhibitor of PLK1 with an IC50 and a Kd of 3 nM and 0.09 nM, respectively, and nearly has no effect on PLK2 and PLK3.

Ro3280,1062243-51-9,Natural Products,PLK, buy Ro3280 , Ro3280 supplier , purchase Ro3280 , Ro3280 cost , Ro3280 manufacturer , order Ro3280 , high purity Ro3280