1818393-16-6
1818393-16-6 structure
- Name: APG-115
- Chemical Name: 15QAU0SI9J
- CAS Number: 1818393-16-6
- Molecular Formula: C34H38Cl2FN3O4
- Molecular Weight: 642.588
- Catalog: Signaling Pathways Apoptosis MDM-2/p53
- Create Date: 2018-06-16 07:38:14
- Modify Date: 2024-01-02 15:36:19
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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].
| Name | 15QAU0SI9J |
|---|---|
| Synonyms |
Bicyclo[2.2.2]octane-1-carboxylic acid, 4-[[[(3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-1'',2''-dihydro-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indol]-5'-yl]carbonyl]amino]-
15QAU0SI9J |
| Description | 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]. |
|---|---|
| Related Catalog | |
| Target |
IC50: 3.8 nm (APG-115)[1] |
| In Vitro | 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 Concentration: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 72 hours Result: Inhibited cell proliferation in a concentration-dependent manner. RT-PCR[3] Cell Line: AGS and MKN45 cells Concentration: 0.02 μM, 0.2 μM Incubation Time: 48 hours Result: Elevated MDM2, p21, PUMA and BAX mRNA expression. Cell Cycle Analysis[3] Cell Line: AGS and MKN45 cells Concentration: 0.02 μM, 0.2 μM Incubation Time: 48 hours Result: Arrested cells at G0/G1 phase. Western Blot Analysis[3] Cell Line: AGS and MKN45 cells Concentration: 0.2 μM Incubation Time: 72 hours Result: Enhanced expressions of MDM2 and p53, stable knockout of p53 abrogated them. Apoptosis Analysis[4] Cell Line: DePTC p53 wide-type cell line: TPC-1 cells, KTC-1 cells Concentration: 0.3μM, 1μM, 3μM, 10 μM Incubation Time: 24 hours Result: Reduced cell population in S-phase, whereas accumulation of cells at G2/M phases. |
| In Vivo | 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] Dosage: 100 mg/kg Administration: Deliverer orally; once daily; 10 days Result: Decreased xenograft tumor growth. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 805.8±65.0 °C at 760 mmHg |
| Molecular Formula | C34H38Cl2FN3O4 |
| Molecular Weight | 642.588 |
| Flash Point | 441.1±34.3 °C |
| Exact Mass | 641.222351 |
| LogP | 7.63 |
| Vapour Pressure | 0.0±3.0 mmHg at 25°C |
| Index of Refraction | 1.658 |