AZD5582

製品コードS7362 バッチS736206

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C58H78N8O8
分子量 1015.29 CAS No. 1258392-53-8
Solubility (25°C)* 体外 Water 50 mg/mL (49.24 mM)
 
 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AZD5582, a novel small-molecule IAP inhibitor, binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP with IC50 values of 15, 21, and 15 nM. AZD5582 induces apoptosis.
in vitro Human pancreatic cancer cells display different sensitivities to the synthetic IAP antagonist, AZD5582. Treating human pancreatic cancer cells with AZD5582 differentially induces apoptosis, dependent on the expression of p-Akt and p-XIAP. It targets cIAP1 to induce TNF-α-induced apoptosis. AZD5582 induces a decrease of Mcl-1 protein, a member of the Bcl-2 family, but not that of Bcl-2 and Bcl-xL[1]. HNSCC (head and neck squamous cell carcinoma) cell lines SCC25, Cal27, and FaDu show a dose-dependent cytotoxic effect after treatment with AZD5582[2].
in vivo After AZD5582 treatment, tumor growth and weight decrease, whereas cleaved caspase 3 expression increases in Panc-1-derived xenograft model[1]. When administered intravenously to MDA-MB-231 xenograft-bearing mice, AZD5582 results in cIAP1 degradation and caspase-3 cleavage within tumor cells and causes substantial tumor regressions following two weekly doses of 3.0 mg/kg. Following a modest 0.5 mg/kg intravenous bolus dose of AZD5582 in mice, unbound plasma levels remain above the concentrations at which apoptosis induction and cell death are observed in MDA-MB-231 cells over the course of several hours. Although cIAP1 degradation happens very quickly upon exposure to AZD5582 in vivo, apoptosis induction (as measured by the amount of cleaved caspase-3) takes longer to reach a maximal effect. A single agent AZD5582 does not exhibit broad-based cytotoxicity but instead should be employed in selected tumor settings expected to be sensitive to IAP inhibitors or in rational combinations with other targeted therapies. The dihydrochloride salt of AZD5582 has sufficient aqueous solubility (>7 mg/mL at pH 4−6) to enable formulation for intravenous administration at the projected efficacious doses. With respect to chemical stability, AZD5582 is found to be photostable and hydrolytically stable between pH 4−6, although some amide hydrolysis is observed under strongly acidic (pH < 1) and basic (pH > 8) conditions. In addition, the compound is stable in the plasma of multiple species, with no compound degradation observed after several hours under physiological conditions[3].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 The human pancreatic cancer cell lines including BxPC-3, Miapaca-2, Panc-1, Panc0813, PL45, Capan-1, Capan-2 and AsPC-1
濃度 0, 0.01, 0.1, 0.5 μM
反応時間 72 h
実験の流れ

DNA or siRNA-transfected or AZD5582-treated cells are collected and cell death is determined by trypan blue exclusion using at least 200∼500 cells. For the MTS assay, pancreatic cancer cells are seeded at 1∼3 × 104 cells/well in a 96-well microtiter plate. The following day, cells are treated with AZD5582, an IAP antagonist, with various doses for 72 h. The MTS assay is performed according to the MTS assay protocol 
動物実験 動物モデル Xenograft tumor (in Balb/c nude mice)
投薬量 3 mg/kg
投与方法 i.v.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

TRAF2/3 deficient B cells resist DNA damage-induced apoptosis via NF-κB2/XIAP/cIAP2 axis and IAP antagonist sensitizes mutant lymphomas to chemotherapeutic drugs [ Cell Death Dis, 2023, 14(9):599] PubMed: 37679334
TRAF2/3 deficient B cells resist DNA damage-induced apoptosis via NF-κB2/XIAP/cIAP2 axis and IAP antagonist sensitizes mutant lymphomas to chemotherapeutic drugs [ Cell Death Dis, 2023, 14(9):599] PubMed: 37679334
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
Mycoplasma hyorhinis infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer [ Heliyon, 2023, 9(10):e20655] PubMed: 37867861
Epigenetic Regulation of HIV-1 Sense and Antisense Transcription in Response to Latency-Reversing Agents [ Noncoding RNA, 2023, 9(1)5] PubMed: 36649034
Epigenetic Regulation of HIV-1 Sense and Antisense Transcription in Response to Latency-Reversing Agents [ Non-Coding RNA, 2023, 9(1), 5] PubMed: None
β-catenin regulates HIV latency and modulates HIV reactivation [ PLoS Pathog, 2022, 18(3):e1010354] PubMed: 35255110
BIRC2-BIRC3 amplification: a potentially druggable feature of a subset of head and neck cancers in patients with Fanconi anemia [ Sci Rep, 2022, 12(1):45] PubMed: 34997070
The Intact Non-Inducible Latent HIV-1 Reservoir is Established In an In Vitro Primary TCM Cell Model of Latency [ J Virol, 2021, JVI.01297-20] PubMed: 33441346
Caspase-1 cleaves Bid to release mitochondrial SMAC and drive secondary necrosis in the absence of GSDMD. [ Life Sci Alliance, 2020, 28;3(6) pii: e202000735] PubMed: 32345661

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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