APG-115

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. APG-115 blocks the interaction of MDM2 and p53 and induces cell-cycle arrest and apoptosis in a p53-dependent manner.

Product information

CAS Number: 1818393-16-6

Molecular Weight: 642.59

Formula: C34H38Cl2FN3O4

Chemical Name: 4-{[(3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indol]-5'-yl]amido}bicyclo[2.2.2]octane-1-carboxylic acid

Smiles: CCN1[C@H]([C@H](C2C=CC=C(Cl)C=2F)[C@@]2(C3=CC=C(Cl)C=C3NC2=O)C21CCCCC2)C(=O)NC12CCC(CC1)(CC2)C(O)=O

InChiKey: YJCZPJQGFSSFOL-MNZPCBJKSA-N

InChi: InChI=1S/C34H38Cl2FN3O4/c1-2-40-27(28(41)39-32-16-13-31(14-17-32,15-18-32)30(43)44)25(21-7-6-8-23(36)26(21)37)34(33(40)11-4-3-5-12-33)22-10-9-20(35)19-24(22)38-29(34)42/h6-10,19,25,27H,2-5,11-18H2,1H3,(H,38,42)(H,39,41)(H,43,44)/t25-,27+,31?,32?,34+/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (155.62 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. APG-115 (0.02 μM, 0.2 μM; 48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose. 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. 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. 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).

In Vivo:

APG-115 (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastric adenocarcinoma in vivo.

Products are for research use only. Not for human use.