YK 4-279 is an inhibitor of RNA Helicase A (RHA) binding to the oncogenic transciption factor EWS-FLI1. YK-4-279 inhibits Ewing’s sarcoma family tumor (ESFT) cell growth; YK-4-279 induces apoptosis.

≥98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

YK 4-279

White or off white solid

DMSO : 25 mg/mL (68.27 mM)

RNA helicase A

YK-4-279 eliminates cyclin D levels by blocking the interaction of EWS-FLI1 with RHA in EWS-FLI1-containing TC32 cells. YK-4-279 also specifically inhibits ESFT cell growth and induces apoptosis. YK-4-279 also inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells, and further decreases cell motility and invasion.

In vivo, YK-4-279 (1.5 mg/dose i.p.) inhibits the growth of ESFT xenograft tumors. In mouse model, YK-4-279 selectively prevents prostate cancer growth and metastasis in fusion-positive LNCaP-luc-M6 tumors.

YK-3-237 is a chalcone derivative and an activator of sirtuin 1 (SIRT1).It inhibits colchicine binding to tubulin in a concentration-dependent manner and tubulin polymerization (IC50 = 31 μM) and induces microtubule loss in A-10 cells (EC50 = 16.5 μM). YK-3-237 inhibits cell growth in a panel of leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast cancer cell lines (GI50s = <0.01-20.9 μM). It inhibits tube formation by human umbilical vein endothelial cells (HUVECs) when used at a concentration of 1 μM and inhibits functional angiogenesis in isolated rat aortic rings. YK-3-237 activates SIRT1 in a concentration-dependent manner and reduces acetylation of wild-type and mutant p53 in a SIRT1-dependent manner. It also inhibits cell growth in panel of 9 triple-negative breast cancer (TNBC) cell lines (EC50s = 0.160-5.031 μM).

≥98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

YK 3-237

Powder

Soluble to 100 mM in DMSO and to 100 mM in ethanol

Ewing’s sarcoma is characterized by the formation of an oncogenic fusion protein, EWS-FLI1, which binds to RNA helicase central to disease. YK-4-279 binds to EWS-FLI1 (K_d = 9.48 μM), blocking the interaction of EWS-FLI1 and RNA helicase and driving apoptosis in Ewing’s sarcoma family tumors.¹ Through these effects, YK-4-279 reduces the growth of Ewing’s sarcoma orthotopic xenografts. Importantly, it is effective in Ewing’s sarcoma cells, both in vitro and in vivo, that are chemotherapy-resistant.² YK-4-279 also binds the ETS transcription factors ERG and ETV1 (K_d = 11.7 and 17.4, respectively), which form fusion proteins that contribute to some types of prostate cancer.³ (+)-YK-4-279 is a highly purified enantiomer of YK-4-279. Its properties have not been characterized.

≥98%

Store at -20℃

1.Erkizan, H.V.,Kong, Y.,Merchant, M., et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing’s sarcoma. Nature Medicine 15(7), 750-756 (2009).

2.Awad, O.,Yustein, J.T.,Shah, P., et al. High ALDH activity identifies chemotherapy-resistant Ewing’s sarcoma stem cells that retain sensitivity to EWS-FLI1 inhibition. PLoS One 5(11), 1-17 (2010).

3.Rahim, S.,Beauchamp, E.M.,Kong, Y., et al. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion. PLoS One 6(4), 1-8 (2011).