Idasanutlin (RG7388)

製品コードS7205 バッチS720502

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

C31H29Cl2F2N3O4
分子量 616.48 CAS No. 1229705-06-9
Solubility (25°C)* 体外 DMSO 100 mg/mL (162.21 mM)
Water Insoluble
Ethanol 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 Idasanutlin (RG7388) is a potent and selective p53-MDM2 inhibitor with IC50 of 6 nM showing improved in vitro binding as well as cellular potency/selectivity.
in vitro Idasanutlin inhibits cell proliferation with IC50 of 30 nM, and induces dose-dependent p53 stabilization, cell cycle arrest, as well as cell apoptosis in cancer cells expressing wild-type p53. [1]
in vivo In a mouse SJSA human osteosarcoma xenograft model, Idasanutlin (25 mg/kg p.o.) causes tumor growth inhibition and regression. [1] In a SJSA xenograft model, Idasanutlin results in induction of apoptosis and antiproliferation. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Biochemical Binding Affinity – HTRF Assay
The p53-MDM2 HTRF assay is performed in buffer containing 50 mM Tris-HCl, pH 7.4, 100 mM NaCl, 1 mM DTT, 0.02 or 0.2 mg/ml BSA. Small-molecule inhibitors are stored in aliquots as 10 mM stock solutions in DMSO at 4°C in 96-deep-well plates. It is thawed and mixed immediately prior to testing. The compound is incubated with GST-MDM2 and a biotinylated p53 peptide for one hour at 37°C. Phycolink goat anti-GST (Type 1) allophycocyanin and Eu-8044-streptavidin are then added and followed by one hour incubation at room temperature. Plates are read using the Envision fluorescence reader. IC50 values are determined from inter-plate duplicate or triplicate sets of data. Data are analyzed by XLfit4 (Microsoft) using a 4 Parameter Logistic Model (Sigmoidal Dose-Response Model) and the equation Y= (A+ ((B-A)/ (1+ ((C/x)^D)))), where A and B are enzyme activity in the absence or presence of infinite inhibitor compound, respectively, C is the IC50 and D is the Hill coefficient.
細胞アッセイ 細胞株 wt-p53 cancer cell lines (SJSA1, RKO, HCT116)
濃度 ~10 μM
反応時間 24 hours
実験の流れ

Cell proliferation is evaluated by the tetrazolium dye assay. The concentration at which 50% inhibition (IC50) or 90% inhibition (IC90) of cell proliferation is determined from the linear regression of a plot of the logarithm of the concentration versus percent inhibition.
動物実験 動物モデル Mice bearing SJSA human osteosarcoma xenografts
投薬量 ~50 mg/kg daily
投与方法 p.o.

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：

Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape [ Nat Commun, 2024, 15(1):1391] PubMed: 38360943
miR-16-5p enhances sensitivity to RG7388 through targeting PPM1D expression (WIP1) in Childhood Acute Lymphoblastic Leukemia [ Cancer Drug Resist, 2023, 6(2):242-256] PubMed: 37457129
Genome-wide CRISPR/Cas9 screening for therapeutic targets in NSCLC carrying wild-type TP53 and receptor tyrosine kinase genes [ Clin Transl Med, 2022, 12(6):e882] PubMed: 35692096
Epstein Barr virus-positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo [ Blood Adv, 2022, 6(3):891-901] PubMed: 34861697
FOXO1 Is a Key Mediator of Glucocorticoid-Induced Expression of Tristetraprolin in MDA-MB-231 Breast Cancer Cells [ Int J Mol Sci, 2022, 23(22)13673] PubMed: 36430156
Novel MDM2 Inhibitor XR-2 Exerts Potent Anti-Tumor Efficacy and Overcomes Enzalutamide Resistance in Prostate Cancer [ Front Pharmacol, 2022, 13:871259] PubMed: 35548335
p53 Regulates a miRNA-Fructose Transporter Axis in Brown Adipose Tissue Under Fasting [ Front Genet, 2022, 13:913030] PubMed: 35734423
Negative value of CD10-/CD34- immunophenotype in pediatric leukemia and development of a related cell line model for investigating drug resistance [ Clin Transl Oncol, 2022, 10.1007/s12094-021-02755-x] PubMed: 34985639
Suppression of HSF1 activity by wildtype p53 creates a driving force for p53 loss-of-heterozygosity [ Nat Commun, 2021, 12(1):4019] PubMed: 34188043
Epstein Barr virus-positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo [ Blood Adv, 2021, bloodadvances.2021006156] PubMed: 34861697

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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