APG-115 (Synonyms: AA-115) |
カタログ番号GC35367
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APG-115 (APG-115) は、それぞれ 3.8 nM および 1 nM の IC50 および Ki 値で MDM2 タンパク質に結合する経口活性 MDM2 タンパク質阻害剤です。 APG-115 は MDM2 と p53 の相互作用を遮断し、p53 依存的に細胞周期の停止とアポトーシスを誘導します。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1818393-16-6
Sample solution is provided at 25 µL, 10mM.
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APG-115 (AA-115) is an orally active MDM2 protein inhibitor binding to MDM2 protein with IC50 and Ki values of 3.8 nM and 1 nM, respectively[1]. APG-115 blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner[2][3]. IC50: 3.8 nm (APG-115)[1]
APG-115 (0.001-100 μM; 72 hours) inhibits cell proliferation in concentration-dependent manner, with IC50s of 18.9 ± 15.6 nM and 103.5 ± 18.3 nM respectively in AGS and MKN45 cells[3].APG-115 (0.02 μM, 0.2 μM; 48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose[3].APG-115 (0.02 μM, 0.2 μM; 48 hours) affects progression by inducing cells arrested at G0/G1 phase in AGS and MKN45 cell with wild p53[3].APG-115 (0.02 μM, 0.2 μM; 24 hours) activates p53 to enhance radiosensitivity in AGS and MKN45 cells; stable knockout of p53 abrogates expression of MDM2, p53, p21, PUMA, BAX, Cleaved-caspase3, γH2AX[3].APG-115 (0.3 μM, 1 μM, 3 μM, 10 μM; 24 hours) leads to a concentration-dependent cell cycle arrest in G2/M phases and a decreasing in S-phase in p53 wide-type cell lines (TPC-1, KTC-1)[4]. Cell Proliferation Assay[3] Cell Line: AGS and MKN45 cells
APG-115 (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastric adenocarcinoma in vivo[3]. Animal Model: Four-week-old male BALB/c athymic nude mice with MKN45 cells[3]
[1]. Angelo Aguilar, et al. 4-((3′R,4′S,5′R)-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development. J Med Chem. 2017 Apr 13; 60(7): 2819-2839. [2]. A W Tolcher et al, A phase Ib/II study of APG-115 in combination with pembrolizumab in patients with unresectable or metastatic melanomas or advanced solid tumors, Ann Oncol. 2019 Feb 1; 30(Supplement_1). pii: mdz027. [3]. Hanjie Yi ea al, A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma, J Exp Clin Cancer Res. 2018 May 2;37(1):97. [4]. Chen H, et al. Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses dedifferentiated papillary thyroid cancer cells. Oncotarget. 2017 Jun 27;8(26):43008-43022.
| Cas No. | 1818393-16-6 | SDF | |
| 同義語 | AA-115 | ||
| Canonical SMILES | O=C1NC2=CC(Cl)=CC=C2[C@]13C4(CCCCC4)N(CC)[C@@H](C(NC56CCC(CC6)(C(O)=O)CC5)=O)[C@@H]3C7=C(C(Cl)=CC=C7)F | ||
| Formula | C34H38Cl2FN3O4 | M.Wt | 642.59 |
| 溶解度 | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5562 mL | 7.781 mL | 15.562 mL |
| 5 mM | 311.2 μL | 1.5562 mL | 3.1124 mL |
| 10 mM | 155.6 μL | 778.1 μL | 1.5562 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)