P53R3
目录号 : GC65961
P53R3 是一种有效的 p53 reactivator，可恢复 p53 热点突变体（包括 p53R175H、p53R248W 和 p53R273H）的序列特异性 DNA 结合。P53R3 以比 PRIMA-1 高得多的特异性诱导 p53 依赖性抗增殖作用。P53R3 增强了野生型 p53 和 p53M237I 向几个靶基因启动子的募集。 P53R3 强烈增强死亡受体死亡受体 5 (DR5) 的 mRNA、总蛋白和细胞表面表达。 P53R3 可以用于癌症研究。
Cas No.:922150-12-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
P53R3 is a potent p53 reactivator and restores sequence-specific DNA binding of p53 hot spot mutants, including p53R175H, p53R248W and p53R273H. P53R3 induces p53-dependent antiproliferative effects with much higher specificity than PRIMA-1. P53R3 enhances the recruitment of wild-type p53 and p53M237I to several target gene promoters. P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5). P53R3 is used for cancer research[1].
P53R3 (10 μg/ml; 24 hours; in the absence or presence of the unlabelled p53 consensus oligonucleotide) restores p53-specific DNA binding activity to p53R273H (a DNA contact mutant) and p53R175H (a structural mutant) in WiDr colon tumour cells harbouring p53R273H and KLE cells with p53R175H[1].
P53R3 (1-33 μg/ml; 24 hours) inhibits the proliferation of the LN-308 sublines expressing mutant p53 plasmids in a p53-dependent manner. The p53R175H-dependent effects are strong over a broad range of concentrations, but p53R273H-dependent effects are weaker and requires high concentrations of P53R3[1].
P53R3 induces p53R248W reactivation is more pronounced proliferation inhibition than observed with p53R273H. P53R3 does not exhibit cytotoxic effects even at concentrations close to its solubility limit (33 μg/ml)[1].
P53R3 (33 μg/ml; 18 hours) induces a strong decrease in S phase cells and a G0/G1 cell cycle arrest in LN-308 p53R175H and LN-308 p53R273H cells. But it does not affect cell cycle distribution of LN-308 p53R248W cells[1].
Cell Viability Assay[1]
| Cell Line: | p53 null LN-308 human glioma cells with a control plasmid or plasmids encoding the mutants p53R175H, p53R248W and p53R273H |
| Concentration: | 1-33 μg/mL |
| Incubation Time: | 24 hours |
| Result: | Induced p53-dependent and -independent antiproliferative and cytotoxic effects in vitro. |
| Cas No. | 922150-12-7 | SDF | Download SDF |
| 分子式 | C32H35Cl2N5O2 | 分子量 | 592.56 |
| 溶解度 | DMSO : ≥ 100 mg/mL (168.76 mM) | 储存条件 | 4°C, stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6876 mL | 8.438 mL | 16.8759 mL |
| 5 mM | 0.3375 mL | 1.6876 mL | 3.3752 mL |
| 10 mM | 0.1688 mL | 0.8438 mL | 1.6876 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells
Pharmaceuticals (Basel) 2022 Jul 2;15(7):824.PMID:35890123DOI:10.3390/ph15070824.
Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures. The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The inhibition of HDAC1/4 (MS275), HDAC1/4/SIRT1/DNMT3a (UVI5008) or EHMT2 (BIX01294) induced a significant reduction on the cell viability, even in gemcitabine-resistance cells. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers. Reverting aberrant epigenetic modifications in combination with gemcitabine offers an alternative treatment for PDAC patients, with an important reduction of the therapeutic dose.
A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis
Cell Death Differ 2008 Apr;15(4):718-29.PMID:18202704DOI:10.1038/sj.cdd.4402301.
Reactivation of mutant p53 in tumours is a promising strategy for cancer therapy. Here we characterise the novel p53 rescue compound P53R3 that restores sequence-specific DNA binding of the endogenously expressed p53(R175H) and p53(R273H) mutants in gel-shift assays. Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R273H) in the p53 null glioma cell line LN-308 reveals that P53R3 induces p53-dependent antiproliferative effects with much higher specificity and over a wider range of concentrations than the previously described p53 rescue drug p53 reactivation and induction of massive apoptosis (PRIMA-1). Furthermore, P53R3 enhances recruitment of endogenous p53 to several target promoters in glioma cells bearing mutant (T98G) and wild-type (LNT-229) p53 and induces mRNA expression of numerous p53 target genes in a p53-dependent manner. Interestingly, P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5) whereas CD95 and TNF receptor 1 levels are unaffected. Accordingly, P53R3 does not sensitise for CD95 ligand- or tumour necrosis factor alpha-induced cell death, but displays synergy with Apo2L.0 in 9 of 12 glioma cell lines. Both DR5 surface induction and synergy with Apo2L.0 are sensitive to siRNA-mediated downregulation of p53. Thus this new p53 rescue compound may open up novel perspectives for the treatment of cancers currently considered resistant to the therapeutic induction of apoptosis.
Elevated ribonucleotide reductase levels associate with suppressed radiochemotherapy response in human cervical cancers
Int J Gynecol Cancer 2012 Nov;22(9):1463-9.PMID:23051959DOI:10.1097/IGC.0b013e318270577f.
Objective: Ribonucleotide reductase (RNR) supplies deoxyribonucleotide diphosphates demanded by cells to repair radiation-induced DNA damage. Here, we investigate the impact of pretherapy RNR M1, M2, and M2b (P53R3) subunit level upon human cervical cancer radiochemosensitivity. Materials/methods: Immunohistochemistry was performed on a tissue array comprised of 18 paired benign uterine cervix and stage IB2 cervical cancers to evaluate the relationship between cytosolic RNR M1, M2, and M2b staining intensity and radiochemotherapy cancer response. Patients underwent surgical hysterectomy (n = 8), or daily radiation (45 Gy), coadministered once-weekly cisplatin (40 mg/m), then low-dose rate brachytherapy (30 Gy) followed by adjuvant hysterectomy (n = 10). Radiochemotherapy response was determined by Response Evaluation Criteria In Solid Tumors version 1.0 criteria during brachytherapy. Cancer relapse rates and disease-free survival were calculated. Results: M1, M2, and M2b antibody staining intensity was low (0-1+) in benign uterine cervical tissue. M1 and M2b immunoreactivity was 2+ or 3+ in most (13/18) cervical cancers. M2 immunoreactivity was 3+ in nearly all (16/18) cervical cancers. Cervical cancers overexpressing M1 and M2b had an increased hazard for incomplete radiochemotherapy response, relapse, and shortened disease-free survival. Conclusions: Ribonucleotide reductase subunit levels may predict human cervical cancer radiochemosensitivity and subsequent posttherapy cancer outcome. Further validation testing of RNR subunits as biomarkers for radiochemotherapy response is warranted.