SAR405838

製品コードS7649 バッチS764901

印刷

化学情報

Chemical Structure Synonyms MI-77301, MI-773 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 (warmed with 50ºC water bath) 31 mg/mL (55.11 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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. This compound 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, this compound (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 this compound 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 of SAR405838 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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/25145672/

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：

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations [ Nat Genet, 2025, 57(1):140-153] PubMed: 39774325
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
Functional diversity of the TP53 mutome revealed by saturating CRISPR mutagenesis [ bioRxiv, 2023, 10.1101/2023.03.10.531074] PubMed: None
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

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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