MI-773 (SAR405838)

製品コードS7649 バッチS764902

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

C29H34Cl2FN3O3
分子量 562.50 CAS No. 1303607-60-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (177.77 mM)
Ethanol 31 mg/mL warmed with 50ºC water bath (55.11 mM)
Water Insoluble
* <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 MI-773 (SAR405838) is an orally available MDM2 antagonist with Ki of 0.88 nM. Phase 1.
in vitro MI-773 binds to MDM2 with Ki of 0.88 nM. MI-773 potently inhibits cell growth in cancer cell lines, including SJSA-1 (IC50, 0.092 μM), RS4;11 (IC50, 0.089 μM), LNCaP (IC50, 0.27 μM), and HCT-116 (IC50, 0.20 μM) cells, and displays high selectivity over cancer cell lines with mutated or deleted p53, including SAOS-2 (IC50, >10 μM), PC-3 (IC50, >10 μM), SW620 (IC50, >10 μM), and HCT-116 (p53-/-) (IC50, >20 μM) cells. [1]
in vivo In the SJSA-1 osteosarcoma, acute lymphoblastic leukemia RS4;11, LNCaP prostate cancer, and HCT-116 colon cancer xenograft model, MI-773 (p.o.) effectively inhibits tumor growth in a dose-dependent manner (10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg,). [1]

プロトコル(参考用のみ)

キナーゼアッセイ Fluorescence-polarization binding assay
Binding affinities of MDM2 inhibitors and p53 peptide to MDM2 protein are determined using an Fluorescence-polarization (FP) binding assay. Binding affinities of MI-773 to Bcl-2, Bcl-xL, Mcl-1, and β-catenin are determined using a competitive FP-based assay, and its binding affinity to MDMx is determined using Biolayer Interferometry technology.
細胞アッセイ 細胞株 SJSA-1, RS4;11, LNCaP, SAOS-2, PC-3, SW620, HCT-116, and HCT-116 (p53-/-) cells
濃度 100 μM
反応時間 ~48 h
実験の流れ Cell growth inhibition activity is determined in a water-soluble tetrazolium-based assay. Cell death is measured by trypan blue staining and apoptosis is determined using an Annexin V-FLUOS staining kit.
動物実験 動物モデル SCID mice with SJSA-1 osteosarcoma (females), acute lymphoblastic leukemia RS4;11 (females), LNCaP prostate cancer (males), or HCT-116 colon cancer (females) xenograft model
投薬量 200 mg/kg
投与方法 p.o.

カスタマーフィードバック

Data from [Data independently produced by , , Oncotarget, 2016, 7(50):82757-82769]

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：

High-Throughput/High Content Imaging Screen Identifies Novel Small Molecule Inhibitors and Immunoproteasomes as Therapeutic Targets for Chordoma [ Pharmaceutics, 2023, 15(4)1274] PubMed: 37111759
BCL6 inhibition ameliorates ruxolitinib resistance in CRLF2-rearranged acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280879] PubMed: 36005560
LIN28B inhibition sensitizes cells to p53-restoring PPI therapy through unleashed translational suppression [ Oncogenesis, 2022, 11(1):37] PubMed: 35780125
Nucleotide biosynthesis links glutathione metabolism to ferroptosis sensitivity [ Life Sci Alliance, 2022, 5(4)e202101157] PubMed: 35074928
Compartmentalization-aided interaction screening reveals extensive high-order complexes within the SARS-CoV-2 proteome [ Cell Rep, 2021, 36(5):109482] PubMed: 34297909
Pharmacogenomics characterization of the MDM2 inhibitor MI-773 reveals candidate tumours and predictive biomarkers [ NPJ Precis Oncol, 2021, 5(1):96] PubMed: 34711913
Paracrine Placental Growth Factor Signaling in Response to Ionizing Radiation Is p53-Dependent and Contributes to Radioresistance [ Mol Cancer Res, 2021, 19(6):1051-1062] PubMed: 33619227
MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1 [ Oncol Lett, 2021, 22(6):838] PubMed: 34712362
MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models [ Cancers (Basel), 2020, 12(8):E2157] PubMed: 32759684
Residual apoptotic activity of a tumorigenic p53 mutant improves cancer therapy responses [ EMBO J, 2019, 38(20):e102096] PubMed: 31483066

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。