AG-14361
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AG-14361是一种选择性的PARP-1抑制剂,Ki50值小于5 nM [1].
PARP1是PRAP家族的成员,在许多细胞过程(比如DNA修复\程序性细胞死亡)中发挥着重要作用.经发现,PARP1在多种肿瘤中异常表达,许多PARP抑制剂已被开发为抗肿瘤药物[1] [2] [3, 4].
AG-14361是一种强效的PARP-1抑制剂.当HR和BRCA2缺陷的细胞与亲代细胞暴露于AG-14361时,即使在非细胞毒性浓度下,HR缺陷的细胞对AG-14361高度敏感,缺乏BRCA2使得细胞对AG-14361更加敏感[5].在人类K562细胞中,AG14361用药16小时可通过抑制PARP-1来显著增强(约2倍)喜树碱(camptothecin)诱发的生长抑制作用(GI50, 16小时, 喜树碱 + AG14361 2.4 ± 0.1 nmol/L)\细胞毒性(LC50, 喜树碱 + AG14361 2.77 ± 0.55 nmol/L),以及DNA单链断裂[1].当用MMR健全细胞(HCT-Ch3\A2780及CP70-ch3)和MMR缺陷细胞(HCT116\CP70及CP70-ch2)测试时,暴露于可抑制PARP1活性的AG-14361后,与MMR缺陷细胞相比,MMR健全细胞对替莫唑胺更敏感[2].
在异种移植BRCA2缺陷细胞和BRCA-2健全肿瘤细胞的小鼠模型中,AG-14361用药后,即使在肿瘤完全消退的情况下,BRCA2缺乏组比BRCA-2健全组更具反应性[5].
参考文献:
[1]. Smith, L.M., 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. 11(23): p. 8449-57.
[2]. Curtin, N.J., et al., Novel poly(ADP-ribose) polymerase-1 inhibitor, AG14361, restores sensitivity to temozolomide in mismatch repair-deficient cells. Clin Cancer Res, 2004. 10(3): p. 881-9.
[3]. Calabrese, C.R., et al., Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst, 2004. 96(1): p. 56-67.
[4]. Veuger, S.J., et al., Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res, 2003. 63(18): p. 6008-15.
[5]. Kyle, S., et al., Exploiting the Achilles heel of cancer: the therapeutic potential of poly(ADP-ribose) polymerase inhibitors in BRCA2-defective cancer. Br J Radiol, 2008. 81 Spec No 1: p. S6-11.
- 1. Megha Jhanji, Chintada Nageswara Rao, et al. "Cis-and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration." Nat Commun. 2022 Jun 10;13(1):3244. PMID: 35688816
- 2. Soni H, Kaminski D, et al. "Cisplatin-induced oxidative stress stimulates renal Fas ligand shedding." Ren Fail. 2018 Nov;40(1):314-322. PMID: 29619879
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 320.39 |
Cas No. | 328543-09-5 |
Formula | C19H20N4O |
Solubility | insoluble in H2O; ≥10.14 mg/mL in EtOH with gentle warming and ultrasonic; ≥16 mg/mL in DMSO |
Chemical Name | 1-(4-((dimethylamino)methyl)phenyl)-8,9-dihydro-2,7,9a-triazabenzo[cd]azulen-6(7H)-one |
SDF | Download SDF |
Canonical SMILES | O=C1N([H])C([H])([H])C([H])([H])N2C3=C1C([H])=C([H])C([H])=C3N=C2C(C([H])=C4[H])=C([H])C([H])=C4C([H])([H])N(C([H])([H])[H])C([H])([H])[H] |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
A549、LoVo和SW620细胞 |
溶解方法 |
在DMSO中的溶解度大于16 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
0.4 μM,5 d |
应用 |
浓度为0.4 μM的AG14361可以抑制85%的PARP-1活性,但是对癌细胞的基因表达和生长没有影响。AG14361增加topotecan和temozolomide的抗增殖效应,抑制LoVo细胞从γ辐射损伤中恢复。 |
动物实验[2]: | |
动物模型 |
6-8周龄的老年雌性裸鼠 |
剂量 |
30 mg/kg,腹腔内给药 |
应用 |
小鼠在移植ES细胞一天前给药,持续9天。和对照组相比,BRCA1-/- ES源性肿瘤的形成减少了90%,而BRCA1+/+ ES源性肿瘤只减少了22%。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Calabrese C R, Almassy R, Barton S, et al. Anticancer chemosensitization and radiosensitization by the novel poly (ADP-ribose) polymerase-1 inhibitor AG14361[J]. Journal of the National Cancer Institute, 2004, 96(1): 56-67. [2]. De Soto J A, Wang X, Tominaga Y, et al. The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors[J]. Int J Biol Sci, 2006, 2(4): 179-185. |
AG14361 is a potent inhibitor of PARP1 with Ki of <5 nM. | ||||||
Targets | PARP1 | |||||
IC50 | < 5 nM (Ki) |
质量控制和MSDS
- 批次: