UC2288 is a novel, cell-permeable, and orally active p21 attenuator (relatively selective activity for p21), which is synthesized based Sorafenib . UC2288 decreases p21 mRNA expression independently of p53, and attenuates p21 protein levels with minimal effect on p21 protein stability. UC2288 has no inhibition of VEGFR2 and Raf kinases even at 10 μM[1].
UC2288 (0-10 μM; 24 hours) decreases p21 protein level, but has no effects on other proteins[1].UC2288 (0-10 μM; 24 hours) decreases p21 mRNA expression transcriptionally or post-transcriptionally but independently of p53[1]. Western Blot Analysis[1] Cell Line: HK2 (normal kidney), 786-O (RCC), Caki-1 (RCC), ACHN (RCC) and HEY (ovarian cancer) cells
UC2888 (oral gavage; 15 mg/kg; 3 times a week; 4 weeks) co-treatment with imetelstat significantly suppresses tumor growth and does not effect mice weight[2].UC2288 (intraperitoneal injection; 10 mg/kg; 4 times in 7 days) attenuates MPTP-induced behavioral impairment, prevents activation of MAPK pathway in the MPTP-treated mice brain. MPTP treatment raises TNF-α, IL-6 and IL-1β levels in MPTP treated mice brain, but UC2288 signicantly decreases MPTP-induced TNF-α, IL-6 levels, but IL-1β is not decreased in brain[3]. Animal Model: Eight-week old, athymic nude (NCr nu/nu) mice injected subcutaneously with HCT116 and ACHN cancer cells(2.5x106)[2]
[1]. Hiromi I Wettersten, et al. A Novel p21 Attenuator Which Is Structurally Related to Sorafenib. Cancer Biol Ther. 2013 Mar;14(3):278-85. [2]. Romi Gupta, et al. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3062-71. [3]. Jun Hyung Im, et al. p21 inhibitor UC2288 ameliorates MPTP induced Parkinson’s disease progression through inhibition of oxidative stress and neuroinammation. Translational Medicine.Neurobiology of Disease