R1530 is a potent and orally active inhibitor of mitosis/angiogenesis [1].
Mitosis is a part of the cell cycle process by which chromosomes in a cell nucleus are separated into two identical sets with each in its own nucleus. Angiogenesis refers to the growth of new blood vessels and is an essential component in the progression and metastasis of tumors [1].
R1530 showed potent inhibitory activities against cyclin-dependent kinases, such as CDK2 and CDK4, and angiogenesis-related growth factor receptor, such as KDR, FGFr, PDGFr, and EGFr [1]. In a series of human tumor cell lines, R1530 inhibited the growth of cells with IC50 values ranging from 0.22 to 3.43 μM. Also, R1530 strongly inhibited human umbilical vein endothelial cells (HUVEC) growth driven by VEGF or bFGF with IC50 values of 49 nM and 118 nM, respectively [2].
In nude mice bearing human H460 tumor xenografts, R1530 (3 to 25 mg/kg, orally twice a day, 20 days) inhibited tumor growth in a dose-dependent way. R1530 (the 25 mg/kg dose) reduced tumor size by 58% in average [3].
References:
[1]. Liu JJ, Higgins B, Ju G, et al. Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors. ACS Med Chem Lett, 2013, 4(2): 259-263.
[2]. Kolinsky K, Tovar C, Zhang YE, et al. Preclinical evaluation of the novel multi-targeted agent R1530. Cancer Chemother Pharmacol, 2011, 68(6): 1585-1594.
[3]. Tovar C, Higgins B, Deo D, et al. Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 2010, 9(16): 3364-3375.