YK-4-279

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Chemical Structure| 1037184-44-3 同义名 : -
CAS号 : 1037184-44-3
货号 : A144944
分子式 : C17H13Cl2NO4
纯度 : 99%+
分子量 : 366.2
MDL号 : MFCD18382120
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
靶点

  • helicase

  • helicase
描述 The erythroblastosis virus E26 transforming sequences (ETS) family of transcription factors consists of a highly conserved group of genes that play important roles in cellular proliferation, differentiation, migration and invasion. ERG and ETV1 are the most commonly translocated ETS proteins, YK-4-279 is a small molecule antagonist of ETV1[3]. Due to its hydrophobic structure, the bioavailability of YK-4-279 is only 2%-15% when it is administered to mice by oral gavage. Intra-peritoneal administrations of 75 mg/kg YK-4-279 initially leads to a steep rise in plasma concentrations, but is substantially cleared leading to ,1 mM levels by 2 hours[4]. Exposure of LNCaP-luc-M6 cells to 1 mM YK-4-279 resulted in significantly reduced mRNA levels of several ETV1 target genes, including MMP7, MMP13, FKBP10 and GLYATL2, without affecting the expression of ETV1[3]. Maximal YK-4-279 concentrations (Cmax) of 90 and 10 μmol/L, respectively, occurred 30 minutes after i.p. or p.o. dosing. YKPO achieved an oral bioavailability of 61% to 73% and peak serum concentration 6.7-fold higher than the half-maximal inhibitory dose observed in vitro (IC50, 1 μmol/L)[5]. The combination of low-dose docetaxel and YK-4-279 synergistically inhibited growth and induced apoptosis in human prostate cancer cells. The combination also more efficiently suppressed the migration and invasion of LNCaP and PC-3 cells. The combination of low-dose docetaxel and YK-4-279 caused a stronger decrease in the levels of ETV1, AR, PSA, p-STAT3,survivin, Bcl-2, and p-Akt in LNCaP cells and of p-Akt, Bcl-2, and p-STAT3 in PC-3 cells compared with either drug alone[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.73mL

0.55mL

0.27mL

13.65mL

2.73mL

1.37mL

27.31mL

5.46mL

2.73mL
参考文献

[1]Rahim S, Beauchamp EM, et al. YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion. PLoS One. 2011 Apr 29;6(4):e19343.

[2]Erkizan HV, Kong Y, et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med. 2009 Jul;15(7):750-6.

[3] Said Rahim, et al. A small molecule inhibitor of ETV1, YK-4-279, prevents prostate cancer growth and metastasis in a mouse xenograft model. PLoS One. 2014 Dec 5;9(12):e114260.

[4]Barber-Rotenberg JS, Selvanathan SP, Kong Y, Erkizan HV, Snyder TM, et al. (2012) Single enantiomer of YK-4-279 demonstrates specificity in targeting the oncogene EWS-FLI1. Oncotarget 3:172–182.

[5] Salah-Eddine Lamhamedi-Cherradi, et al. An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma. Mol Cancer Ther. 2015 Jul;14(7):1591-604.

[6]Lin Yu,et al. The Effects and Mechanism of YK-4-279 in Combination with Docetaxel on Prostate Cancer. Int J Med Sci. 2017 Apr 7;14(4):356-366.