APG-115 free base · Synonyms: Alrizomadlin | AA-115

Alrizomadlin (APG-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.

For research use only. Not for human or veterinary use.

Target MDM-2/p53 E1/E2/E3 Enzyme Apoptosis

Research area Cancer

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Data Sheet SDS COA

APG-115 structure

CAS No.: 1818393-16-6

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 485.00	BP-01934-100mg	In stock	Get quote
250 mg	USD 985.00	BP-01934-250mg	In stock	Get quote
500 mg	USD 1,585.00	BP-01934-500mg	In stock	Get quote
1 g	Inquire	BP-01934-1g	In stock	Inquire
2 g	Inquire	BP-01934-2g	Inquire	Inquire

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Description

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

Biological activity

In Vitro Alrizomadlin (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. Alrizomadlin (0.02 μM, 0.2 μM; 48 hours) enhances the anti-proliferative effect of radiotherapy at different radiation dose. Alrizomadlin (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. Alrizomadlin (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. Alrizomadlin (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 Alrizomadlin (Delivered orally; 100 mg/kg; once daily; 10 days) enhances radiation antitumor effect in gastric adenocarcinoma in vivo.

Identifiers

SMILES: O=C1[C@]2(C3=CC=C(Cl)C=C3N1)C4(CCCCC4)N([C@H]([C@@H]2C5=C(C(Cl)=CC=C5)F)C(NC67CCC(CC6)(CC7)C(O)=O)=O)CC
InChIKey: YJCZPJQGFSSFOL-MNZPCBJKSA-N

Specifications

MW (average): 642.5880
Formula: C₃₄H₃₈Cl₂FN₃O₄
CAS No.: 1818393-16-6
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃ 3 years; 4℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO 100 mg/mL

Documents

References

[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 Do

[2]. A W Tolcher et al, A phase Ib/II study of APG-115 in combination with MK-3475 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.

Same target

Search MDM-2/p53

Same research area

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