AA-115

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AA-115 (APG 115) 是一种有效的口服活性 MDM2 抑制剂，Ki <1 nM，有效抑制 SJSA-1 细胞生长，IC50 为 60 nM。

AA-115 (APG 115) is a potent and orally active MDM2 inhibitor with Ki <1 nM, potently inhibits SJSA-1 cell growth with IC50 of 60 nM; exhibits IC50 values of 38, 18, and 104 nM in the RS4;11 acute leukemia, LNCaP prostate cancer, and HCT116 colon cancer cell lines, respectively; effectively inhibits tumor growth and causes no or minimal weight loss.

Cell Proliferation Assay Cell Line:AGS and MKN45 cells Concentration:0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μMIncubation Time:72 hours Result:Inhibited cell proliferation in a concentration-dependent manner.RT-PCRCell 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 Cell Line:AGS and MKN45 cells Concentration:0.02 μM, 0.2 μM Incubation Time:48 hoursResult:Arrested cells at G0/G1 phase.Apoptosis Analysis 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.Western Blot Analysis 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.

Animal Model:Four-week-old male BALB/c athymic nude mice with MKN45 cells Dosage:100 mg/kg Administration:Deliverer orally; once daily; 10 days.Result:Decreased xenograft tumor growth.

AA115 | APG 115

Apoptosis

MDM2-p53

MDM2-p53

Cancer

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1818393-16-6

642.593

C34H38Cl2FN3O4

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (155.62 mM)

O=C1NC2=CC(Cl)=CC=C2[C@]13C4(CCCCC4)N(CC)[C@@H](C(NC5(CC6)CCC6(C(O)=O)CC5)=O)[C@@H]3C7=C(F)C(Cl)=CC=C7

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

(-20℃)

With Ice Pack

≥ 2 years