UC2288

A cell-permeable compound that selectively downregulates the expression of p21 (~10 µM), independent of p53.expression, at either transcription or post-transcriptional level.

A cell-permeable phenylcyclohexyl-urea compound that downregulates cellular p21/Cip1/CKI/Waf1 protein level (by >95% in HCT116 cells after 24 h UC2288 treatment at 2.5 µM), presumably by means of a yet undetermined transcriptional or post-transcriptional regulation without affecting p21 cellular half-life or inhibiting the kinase activities of C-raf, B-raf^V600E, or VEGFR2 (IC₅₀ >10 µM). Dual telomerase and p21, but not p16 or p27 (gene = CDKN1A, CDKN2A, CDKN1B, respectively), knockdown/inhibition is demonstrated to effectively kill cancer cells both in vitro (% viability inhibition/% Annexin V+ cells induction = 20%/2% or 77%/55%, respectively, following telomerase inhibition by Imetelstat with or without 2.5 µM UC2288 for 24 h in HCT116 colon cancer cultures) and in mice in vivo (% tumor expansion suppression by UC2288 alone/Imetelstat alone/combined treatment = 13%/42%/90%/HCT116 and 4%/23%/92%/ACHN; 30 mg Imetelstat/kg via i.p. and/or 15 mg UC2288/kg via p.o. 3X/wk for 3 wk) by inducing p53- and E2F1-dependent PUMA expression, while p21 overexpression, p53 inactivation by mutation, shRNA-mediated E2F1 or PUMA downregulation abolishes such synergized cell killing. Likewise, reactivating mutant p53 activitiy by CP-31398 (Cat. No. 506166) treatment is reported to resensitize DLD1 (p53 S241F) and A375.S2 (p53 R273H & P309S) to p21 shRNA- & Imetelstat-induced apoptotic cell death and tumor growth inhibition.

Cell permeable: yes

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Use only fresh DMSO for reconstitution.

Gupta, R., et al. 2014. Proc. Natl. Acad. Sci. USA111, E3062.
Wettersten, H.I., et al. 2013. Cancer Biol. Ther.14, 278.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)