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PRT4165

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Chemical Structure| 31083-55-3 同义名 : NSC600157
CAS号 : 31083-55-3
货号 : A295342
分子式 : C15H9NO2
纯度 : 98%+
分子量 : 235.238
MDL号 : MFCD00435709
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(106.28 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • E3 Ligase

    Bmi1/Ring1A, IC50:3.9 μM
描述 Polycomb-repressive complex 1 (PRC1) is a histone H2A/H2AX E3 ubiquitin ligase. PRC1 has a critical role in the regulation of differentiation and the maintenance of stem cell populations[2]. PRT4165 is a potent inhibitor of PRC1-mediated H2A ubiquitylation that inhibits the PRC1 subunits BMI1/RING1 with IC50 value of 3.9μM[3]. In vitro, treatment with 50μM PRT4165 in A375 cells or 100μM in Hela cells for 3h leaded to disappearance of the speckled staining in the nuclei and appearance of Bmi1 also in the cytoplasm[3]. PRT4165 inhibited H2AUB and sphere formation with IC50 values of 3.52mM and 1.05mM in PC3 cells [4]. Treatment PRT4165 at dose of 50μM PRT4165 suppressed growth of leukemia cell lines THP-1, TMD7, OCI/AML772, OCI/AML5, Jurkat and KOPT-K1 by apoptosis. In addition, PRT4165 inhibited the expression of NOTCH1 in KOPT-K1, OCI/ALML2 and OCI/AML5 cells. PRT4165 also inhibited the expression of NOTCH1, MYC, and HES1 in KOPT-K1 cells[5]. In vivo, administration of 8mg/kg PRT4165 caused disruption of decidualization and polyploidy development during early pregnancy by inhibition of PRC1 in mice[6].
作用机制 PRT4165 inhibits PRC1-mediated histone H2A ubiquitylation and the accumulation of ubiquitin at the DNA double-strand break sites [2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.25mL

0.85mL

0.43mL

21.26mL

4.25mL

2.13mL

42.51mL

8.50mL

4.25mL
参考文献

[1]Ismail IH, McDonald D, et al. A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. J Biol Chem. 2013 Sep 13;288(37):26944-54.

[2] Ismail IH. A small molecule inhibitor of polycomb repressive complex 1 inhibits ubiquitin signaling at DNA double-strand breaks. J Biol Chem. 2013 Sep 13;288(37):26944-54. doi: 10.1074/jbc.M113.461699. Epub 2013 Jul 30.

[3] Alchanati I. The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target. PLoS One. 2009 Dec 1;4(12):e8104. doi: 10.1371/journal.pone.0008104.

[4]Su W. The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer Metastasis by Coordinating Stemness and Immune Suppression. Cancer Cell. 2019 Aug 12;36(2):139-155.e10. doi: 10.1016/j.ccell.2019.06.009. Epub 2019 Jul 18.

[5]Ohtaka M, Itoh M, Tohda S. BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute Leukemia Cells. Anticancer Res. 2017 Nov;37(11):6047-6053. doi: 10.21873/anticanres.12052.

[6]Bian F. Polycomb repressive complex 1 controls uterine decidualization. Sci Rep. 2016 May 16;6:26061. doi: 10.1038/srep26061.