AG14361

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Chemical Structure| 328543-09-5 同义名 : -
CAS号 : 328543-09-5
货号 : A813703
分子式 : C19H20N4O
纯度 : 98+%
分子量 : 320.388
MDL号 : MFCD18385009
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(28.09 mM)，配合低频超声，并水浴加热至45℃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

  • PARP1

    PARP1, Ki:<5 nM
描述 Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites[3]. AG14361 is a potent PARP-1 inhibitor, with a Ki of < 5 nM, and in permeabilized SW620 and intact SW620 cells, the IC50s are 29 nM and 14 nM, respectively. AG14361 inhibits the proliferation of human cancer cells, such as A549, LoVo, and SW620 cells, with GI50s of 14 μM, 11.2 μM and 20 μM, respectively[4].AG14361 suppresses breast cancer cells with IC50s of 17 μM and 25 μM for 92 J-wt-BRCA1 and 92 J-sh-BRCA1 cells, respectively. AG14361 induces caspase 3/7 activation and cell cycle abnormalities, and also inhibits NF-κB signaling. AG14361 (5 and 15 mg/kg, i.p.) has no toxicity and does not inhibit the growth of tumor. However, AG14361 markedly enhances NSC 362856 activity against LoVo xenografts and delays tumor growth when combined with NSC 362856. AG14361 (15 mg/kg, i.p.) treatment before irradiation dramaticly increases the sensitivity to radiation therapy of mice bearing LoVo xenografts. AG14361 (30 mg/kg) synergizes lestaurtinib activity on inhibiting breast cancer tumors in allografts[5].AG14361 suppresses breast cancer cells with IC50s of 17 μM and 25 μM for 92 J-wt-BRCA1 and 92 J-sh-BRCA1 cells, respectively. AG14361 induces caspase 3/7 activation and cell cycle abnormalities, and also inhibits NF-κB signaling[2]. AG14361 (0.4 μM) enhances the growth-inhibitory and cytotoxic effects of topoisomerase I poisons, with no obvious effect on the formation and reversal of cleavable complexes, and increases the persistence of camptothecin-induced DNA single-strand breaks[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
LoVo cells Function assay Concentration that gives 50% growth inhibition in LoVo cells, activity expressed as GI50, GI50=11.2 μM 12519059
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.12mL

0.62mL

0.31mL

15.61mL

3.12mL

1.56mL

31.21mL

6.24mL

3.12mL
参考文献

[1]Calabrese CR, Almassy R, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004 Jan 7;96(1):56-67.

[2]Curtin NJ, Wang LZ, et al. Novel poly(ADP-ribose) polymerase-1 inhibitor, AG14361, restores sensitivity to temozolomide in mismatch repair-deficient cells. Clin Cancer Res. 2004 Feb 1;10(3):881-9.

[3]Yijie Wang,et al. PARP-1 and its associated nucleases in DNA damage response. DNA Repair (Amst). 2019 Sep;81:102651.

[4]Calabrese CR, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004 Jan 7;96(1):56-67.

[5] Vazquez-Ortiz G, et al. Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Breast Cancer Res. 2014 Jun 24;16(3):R67.

[6]Smith LM, et al. The novel poly(ADP-Ribose) polymerase inhibitor, AG14361, sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks. Clin Cancer Res. 2005 Dec 1;11(23):8449-57.