APG-115-AA-115-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAPG-115Cat. No.: HY-101518CAS No.: 1818393-16-6Synonyms: AA-115分式: CHClFNO分量: 642.59作靶点: MDM-2/p53; Apoptosis作通路: Apoptosis储存式: Please store the product under the recommended conditions inthe COA.BIOLOGICAL ACTIVITY物活性 APG-115 (

2、AA-115)种服活性分 MDM2 蛋抑制剂, 可与 MDM2 蛋结合，IC50 值和 Ki 值分别为3.8 nM 和 1 nM。APG-115 可阻断 MDM2 与 p53 的相互作并且以 p53 依赖性式诱导细胞周 期停滞和凋亡(apoptosis)。IC50 & Target IC50: 3.8 nm (APG-115) 1体外研究APG-115 (0.001-100 M; 72 hours) inhibits cell proliferation in concentration-dependent manner, with IC50sof 18.915.6 nM and 103.51

3、8.3 nM respectively in AGS and MKN45 cells 3.APG-115 (0.02 M, 0.2 M;48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose 3.APG-115 (0.02 M, 0.2 M; 48 hours) affects progression by inducing cells arrested at G0/G1 phase in AGS and MKN45 cellwith wild p53 3.APG-

4、115 (0.02 M, 0.2 M; 24 hours) activates p53 to enhance radiosensitivity in AGS andMKN45 cells; stable knockout of p53 abrogates expression of MDM2, p53, p21, PUMA, BAX, Cleaved-caspase3, H2AX 3.APG-115 (0.3 M, 1 M, 3 M, 10 M; 24 hours) leads to a concentration-dependentcell cycle arrest in G2/M phas

5、es and a decreasing in S-phase in p53 wide-type cell lines (TPC-1, KTC-1) 4.Cell Proliferation Assay 3Cell Line: AGS and MKN45 cellsConcentration: 0.0001 M, 0.001 M, 0.01 M, 0.1 M, 1 M, 10 M, 100 MIncubation Time: 72 hours1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEResult: Inhibited cell prolif

6、eration in a concentration-dependent manner.RT-PCR 3Cell Line: AGS and MKN45 cellsConcentration: 0.02 M, 0.2 MIncubation Time: 48 hoursResult: Elevated MDM2, p21, PUMA and BAX mRNA expression.Cell Cycle Analysis 3Cell Line: AGS and MKN45 cellsConcentration: 0.02 M, 0.2 MIncubation Time: 48 hoursResu

7、lt: Arrested cells at G0/G1 phase.Western Blot Analysis 3Cell Line: AGS and MKN45 cellsConcentration: 0.2 MIncubation Time: 72 hoursResult: Enhanced expressions of MDM2 and p53, stable knockout of p53 abrogated them.Apoptosis Analysis 4Cell Line: DePTC p53 wide-type cell line: TPC-1 cells, KTC-1 cel

8、lsConcentration: 0.3M, 1M, 3M, 10 MIncubation Time: 24 hoursResult: Reduced cell population in S-phase, whereas accumulation of cells at G2/M phases.体内研究APG-115 (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastricadenocarcinoma in vivo 3.Animal Model: Fou

9、r-week-old male BALB/c athymic nude mice with MKN45 cells 3Dosage: 100 mg/kg2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAdministration: Deliverer orally; once daily; 10 daysResult: Decreased xenograft tumor growth.REFERENCES1. Angelo Aguilar, et al. 4-(3R,4S,5R)-6-Chloro-4-(3-chloro-2-fluorophe

10、nyl)-1-ethyl-2-oxodispirocyclohexane-1,2-pyrrolidine-3,3-indoline-5-carboxamido)bicyclo2.2.2octane-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): 28192839.2. A W Tolcher et al, A phase Ib/

11、II study of APG-115 in combination with pembrolizumab in patients with unresectable or metastaticmelanomas 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 ExpClin 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 cancercells. Oncotarget. 2017 Jun 27;8(26):43008-43022.McePdfHeightCaution: Prod