RG-7112

製品コードS7030 バッチS703002

印刷

化学情報

Chemical Structure Synonyms RO5045337 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C38H48Cl2N4O4S
分子量 726.28 CAS No. 939981-39-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (137.68 mM)
Ethanol 100 mg/mL (137.68 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 RG7112 (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor with HTRF IC50 of 18 nM.
in vitro RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies. RG7112 binds MDM2 with high affinity (KD of 10.7 nM), blocking its interactions with p53 in vitro. A crystal structure of the RG7112–MDM2 complex reveals that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activates the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 shows potent antitumor activity against a panel of solid tumor cell lines. However, its apoptotic activity varies widely with the best response observed in osteosarcoma cells with MDM2 gene amplification. [1]
in vivo RG7112 activates p53 pathway and induces apoptosis in tumor cells in vivo. Oral administration of RG7112 to human xenograft-bearing mice at nontoxic concentrations caused dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. Notably, RG7112 is highly synergistic with androgen deprivation in LNCaP xenograft tumors. [1]

プロトコル(参考用のみ)

キナーゼアッセイ p53-MDM2 binding assay
Homogeneous time-resolved fluorescence (HTRF) assay measures the signal generated by 2 components when they are in close proximity. The p53–MDM2 binding assay uses a biotinylated peptide derived from the MDM2-binding domain of p53 and a truncated N-terminal portion of recombinant human GST-tagged MDM2 protein containing the p53-binding domain. Proteins for crystal structure studies are expressed in E. coli strain BL21 using the helper plasmid pUBS 520 coding for the lacIq repressor and the rare tRNAArg [AGA/AGG]. For crystallization, the frozen protein is thawed and concentrated to 9.8 mg/mL using a Centricon concentrator (3,000 MW cutoff). The complex is then formed by combining the protein with a slight molar excess of the inhibitor (stock solution is 100 mM in DMSO) and this solution is allowed to sit for 4 hours at 4°C. Cryopreserved crystals are used to collect diffraction data on beamline X8C.
動物実験 動物モデル SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice
投薬量 25–200 mg/kg
投与方法 oral

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：

Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs [ Biomolecules, 2023, 13(8)1257] PubMed: 37627322
Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs [ Biomolecules, 2023, 13(8)1257] PubMed: 37627322
Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells [ Cancers -Basel), 2023, 15(17)4326] PubMed: 37686602
Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells [ Cancers (Basel), 2023, 15(17)4326] PubMed: 37686602
Combined Mcl-1 and YAP1/TAZ inhibition for treatment of metastatic uveal melanoma [ Melanoma Res, 2023, 10.1097/CMR.0000000000000911] PubMed: 37467061
Multi-omics analysis reveals the mechanisms of action and therapeutic regimens of traditional Chinese medicine, Bufei Jianpi granules: Implication for COPD drug discovery [ Phytomedicine, 2022, 98:153963] PubMed: 35121390
Poroptosis: A form of cell death depending on plasma membrane nanopores formation [ iScience, 2022, 25(6):104481] PubMed: 35712073
Cell cycle block by p53 activation reduces SARS-CoV-2 release in infected alveolar basal epithelial A549-hACE2 cells [ Front Pharmacol, 2022, 13:1018761] PubMed: 36582523
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746
Preclinical Evaluation of Trabectedin in Combination With Targeted Inhibitors for Treatment of Metastatic Uveal Melanoma [ Invest Ophthalmol Vis Sci, 2022, 63(13):14] PubMed: 36515935

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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