YK 3-237

YK-3-237, a SIRT1 activator, targets mutant p53. YK-3-237 inhibits the proliferation of triple-negative breast cancer cells[1].

Signaling Pathways >> Epigenetics >> Sirtuin

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin

SIRT1

YK-3-237 exhibits the anti-proliferative activities toward most of the breast cancer cell lines tested at submicromolar concentration. YK-3-237 preferentially inhibits the proliferation of breast cancer cell lines carrying mtp53[1]. YK-3-237 inhibits the proliferation of triple-negative breast cancer (TNBC) HS578T, MDA-MB-453, SUM1315MO2, SUM149PT, BT549, MDA-MB-231, MDA-MB-436, MDA-MB-468, HCC1937 with IC50s of 0.160±0.043, 0.241±0.086, 0.253±0.028, 0.289±0.066, 0.353±0.017, 0.431±0.136, 0.501±0.062, 1.436±0.754, 5.031±2.010 µM, respectively[1]. YK-3-237 inhibits the proliferation of Luminal T47D, MCF7, and ZR-75-1 with IC50s of 1.573±0.370, 2.402±0.256, 3.822±0.967 µM, respectively[1]. YK-3-237 inhibits the proliferation of HER2 BT474 and SK-BR-3 with IC50s of 1.249±0.372 and 0.346±0.066 µM, respectively[1]. YK-3-237 (0.01-10 µM; 24 hours) deacetylates mtp53 in TNBC cell lines[1]. YK-3-237 is a potent activator of Sirt1, on the activation of renal interstitial fibroblasts using NRK-49F cells[2]. Exposure of cells to YK-3-237 also significantly reduces expression of α-SMA and fibronectin in a dose-dependent manner, with the maximum inhibition occurring at 10 μM[2]. Cell Viability Assay[1] Cell Line: BT549, MDA-MB-468, HS578T, SUM149PT Concentration: 0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 µM Incubation Time: 24 hours Result: Reduced both the acetylation of K382 and the level of mtp53 in a dose-dependent manner in mtp53 TNBC cell lines.

[1]. Yong Weon Yi, et al. Targeting mutant p53 by a SIRT1 activator YK-3-237 inhibits the proliferation of triple-negative breast cancer cells. Oncotarget. 2013 Jul;4(7):984-94.

[2]. Murugavel Ponnusamy, et al. Activation of Sirtuin-1 Promotes Renal Fibroblast Activation and Aggravates Renal Fibrogenesis. J Pharmacol Exp Ther. 2015 Aug;354(2):142-51.