Nutlin-3a chiral
(Synonyms: Nutlin-3a;Nutlin 3a) 目录号 : GC10470
Nutlin-3a 手性是 Nutlin-3 的活性异构体，是鼠类双微体 2 (MDM2) 拮抗剂，IC50 值为 0.09μM。
Cas No.:675576-98-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Nutlin-3a chiral, an active isomer of Nutlin-3, is a murine double microbody 2 (MDM2) antagonist with IC50 value of 0.09μM . Nutlin-3a chiral inhibits MDM2-p53 interaction and activates wild-type p53, inducing cell cycle arrest and apoptosis[2].
Incubation with 10 μm Nutlin-3a chiral for 7 days resulted in > 90% inhibition of NIH/3T3 cell growth but did not affect MEF proliferation, in which both targets of the drug were eliminated[3].
Nutlin-3a chiral was able to increase the sensitivity to BBR and certain NAX compounds. The effects of Nutlin-3a chiral were usually more substantial in those cells containing an introduced WT TP53 gene[6]. Nutlin-3a chiral binds MDM2 in the TP53-bindingpocket, thereby interfering with MDM2-directed TP53 degradation. This has been shown to cause cell cycle arrest, growth inhibitionand apoptosis in both solid tumors and lymphoid neoplasms.In mantle cell lymphoma(MCL), Nutlin-3a chiral can inhibit cell growth and activate apoptosis in bothwt-TP53(IC50 of 1 to 10μM) and mt-TP53(IC50 of 22.5μM) cells[4]. Nutlin-3a chiral can also effectcell cycle in gastric cancer cell lines. It induces G1 arrest inMKN-45 and SNU-1 cell lines[5].LA-N-5(human neuroblastoma) and SMS-KCNR cells pretreated with Nutlin-3a chiral were significantly more susceptible to DNAM-1-engineered NK cells than NK cells transfected with the empty vector suggesting that the combined use of DNAM-1-chimeric receptor-engineered NK cells and Nutlin-3a chiral may represent a novel therapeutic approach for the treatment of solid tumors, such as NB, carrying dysfunctional p53[7].
In Sjsa-1 tumor-bearing nude mice, Nutlin-3a chiral inhibited xenograft growth in a dose-dependent manner, with the highest dose (200 mg/kg) showing significant tumor shrinkage[3].
References:
[1]: Yang X, Liu J, et,al. miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities. Oncogenesis. 2021 Feb 12;10(2):15. doi: 10.1038/s41389-021-00304-3. PMID: 33579899; PMCID: PMC7881152.
[2]: Crane EK, Kwan SY, et,al. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas. PLoS One. 2015 Aug 6;10(8):e0135101. doi: 10.1371/journal.pone.0135101. PMID: 26248031; PMCID: PMC4527847.
[3]: Tovar C, Rosinski J, et,al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27. PMID: 16443686; PMCID: PMC1413632.
[4]: Roscoe I, Parker M, et,al. Human Serum Albumin and the p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells. Mol Pharm. 2018 Nov 5;15(11):5046-5057. doi: 10.1021/acs.molpharmaceut.8b00647. Epub 2018 Oct 10. PMID: 30226785.
[5]: Chen R, Zhou J, et,al. A Fusion Protein of the p53 Transaction Domain and the p53-Binding Domain of the Oncoprotein MdmX as an Efficient System for High-Throughput Screening of MdmX Inhibitors. Biochemistry. 2017 Jun 27;56(25):3273-3282. doi: 10.1021/acs.biochem.7b00085. Epub 2017 Jun 14. PMID: 28581721.
[6]: Abrams SL, Akula SM, et,al. Effects of the MDM2 inhibitor Nutlin-3a on sensitivity of pancreatic cancer cells to berberine and modified berberines in the presence and absence of WT-TP53. Adv Biol Regul. 2022 Jan;83:100840. doi: 10.1016/j.jbior.2021.100840. Epub 2021 Nov 23. PMID: 34866036.
[7]: Focaccetti C, Benvenuto M, et,al. DNAM-1-chimeric receptor-engineered NK cells, combined with Nutlin-3a, more effectively fight neuroblastoma cells in vitro: a proof-of-concept study. Front Immunol. 2022 Jul 28;13:886319. doi: 10.3389/fimmu.2022.886319. PMID: 35967339; PMCID: PMC9367496.
Nutlin-3a 手性是 Nutlin-3 的活性异构体,是鼠类双微体 2 (MDM2) 拮抗剂,IC50 值为 0.09μM。 Nutlin-3a 手性抑制 MDM2-p53 相互作用并激活野生型 p53,诱导细胞周期停滞和细胞凋亡[2]。
与 10 μm Nutlin-3a 手性孵育 7 天产生 >； 90%抑制NIH/3T3细胞生长但不影响MEF增殖,药物的两个靶点均被消除[3]。
Nutlin-3a 手性能够提高对 BBR 和某些 NAX 化合物的敏感性。 Nutlin-3a 手性的作用通常在那些含有引入的 WT TP53 基因的细胞中更为显着[6]。 Nutlin-3a 手性结合 TP53 结合袋中的 MDM2,从而干扰 MDM2 定向的 TP53 降解。这已被证明会导致实体瘤和淋巴肿瘤的细胞周期停滞、生长抑制和细胞凋亡。在套细胞淋巴瘤 (MCL) 中,Nutlin-3a 手性可抑制细胞生长并激活 wt-TP53 的细胞凋亡（IC50 为 1 至 10μM ) 和 mt-TP53(IC50 为 22.5μM) 细胞[4]。 Nutlin-3a 手性也可以影响胃癌细胞系的细胞周期。它在 MKN-45 和 SNU-1 细胞系中诱导 G1 期阻滞[5]。用 Nutlin-3a 手性预处理的 LA-N-5（人神经母细胞瘤）和 SMS-KCNR 细胞对 DNAM 更敏感-1 工程 NK 细胞比用空载体转染的 NK 细胞表明 DNAM-1 嵌合受体工程 NK 细胞和 Nutlin-3a 手性的联合使用可能代表治疗实体瘤的新治疗方法,例如注意,携带功能失调的 p53[7]。
在 Sjsa-1 荷瘤裸鼠中,Nutlin-3a 手性以剂量依赖的方式抑制异种移植物的生长,最高剂量（200 mg/kg）显示出显着的肿瘤缩小[3].
| Cell experiment [1]: | |
|
Cell lines |
Mouse NIH/3T3 fibroblasts |
|
Preparation Method |
Exponentially growing mouse NIH/3T3 fibroblasts (wt-TP53) were incubated for 7 days in the presence of Nutlin-3a chiral and stained live by acridine orange. |
|
Reaction Conditions |
10 μM Nutlin-3a chiral for 7 days |
|
Applications |
When tested the activity of Nutlin-3a chiral, on exponentially proliferating mouse NIH/3T3 fibroblasts that express wild-type p53, Seven days of incubation with 10 μM Nutlin-3a chiral led to >90% inhibition of NIH/3T3 cells growth. |
| Animal experiment [2]: | |
|
Animal models |
Sjsa-1 tumor-bearing nude mice |
|
Preparation Method |
Mice were given an oral dose of 200 mg/kg Nutlin-3a chiral twice daily for 2 weeks (LnCaP and 22Rv1) or 3 weeks (MHM) |
|
Dosage form |
200mg/kg Nutlin-3a chiral for 2 or 3 weeks |
|
Applications |
Nutlin-3a chiral inhibited xenograft growth in a dose-dependent manner, with the highest dose (200 mg/kg) showing significant tumor shrinkage |
|
References: [1]. Tovar C, Rosinski J, et,al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. doi: 10.1073/pnas.0507493103. Epub 2006 Jan 27. PMID: 16443686; PMCID: PMC1413632. |
|
| Cas No. | 675576-98-4 | SDF | |
| 别名 | Nutlin-3a;Nutlin 3a | ||
| 化学名 | 4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one | ||
| Canonical SMILES | CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl | ||
| 分子式 | C30H30Cl2N4O4 | 分子量 | 581.49 |
| 溶解度 | ≥ 29.0745 mg/mL in DMSO, ≥ 104.4 mg/mL in EtOH | 储存条件 | Store at -20°C,protect from light |
| 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7197 mL | 8.5986 mL | 17.1972 mL |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL |
| 10 mM | 0.172 mL | 0.8599 mL | 1.7197 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet