RO4929097 (RG-4733)

製品コードS1575 バッチS157506

印刷

化学情報

Chemical Structure Synonyms RG-4733 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H20F5N3O3
分子量 469.4 CAS No. 847925-91-1
Solubility (25°C)* 体外 DMSO 93 mg/mL (198.12 mM)
Ethanol 93 mg/mL (198.12 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.
Clear solution
5%DMSO 95%saline

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.200mg/ml (0.43mM) Taking the 1 mL working solution as an example, add 50 μL of 4 mg/ml clear DMSO stock solution to 950 μL of saline and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 4.700mg/ml (10.01mM) Taking the 1 mL working solution as an example, add 50 μL of 94 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
in vitro RO4929097 decreases the amount of Aβ peptides secreted into the culture medium in HEK293 cells with EC50 of 14 nM. This compound strongly inhibits Notch processing with EC50 of 5 nM in the Notch cell-based reporter assay. The potency of this chemical in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity observed with respect to 75 other proteins of various types including receptors, ion channels, and enzymes (CEREP panel). After 5 days of treatment, it reduces the production of ICN in the human NSCLC A549 cells inducing a flattened and less transformed tumor cell phenotype in tissue culture. [1] It blocks Notch processing in human non-small cell lung carcinoma cells and decreases expression of the Notch transcriptional target gene Hes1. Treatment with this compound reveals a two- to threefold decrease in the expression of direct Notch target genes, Hes1, Hey1, and Heyl in SUM149 and a 3.5- to eightfold decrease in expression in SUM190 cells. It modestly inhibits the growth of SUM149 cells in a dose-dependent manner. At a concentration of 1 μM of this chemical, growth inhibition is 20 % for SUM149 and 10 % for SUM190 cells, relative to vehicle-treated controls. It decreases the production of inflammatory cytokines by T-cells. Furthermore, with this treatment, there is a shift in favor of TH2 over TH1 cytokines. In addition, T-cell activation induced IL-6 production would be increased with this compound. [2] Upon this treatment, the selected melanoma cell lines reveals downregulation of NOTCH downstream effector HES1. A decrease in the amount of melanospheres formed upon this treatment in primary melanoma cell lines is detected. [3]
in vivo Oral injection of 3 to 60 mg/kg RO4929097 once daily or twice daily to nude mice bearing A549 NSCLC xenografts for either 7, 14, or 21 days of a 21-day schedule results in significant tumor growth inhibition compared with vehicle-treated animals. The tumor growth inhibition values ranges from 66% to 91%. When mice are treated with 60 mg/kg of this compound twice daily with the 7+/14- schedule, treatment initially arouses regression of established A549 tumors. At the end of the 21-day cycle (day 47), tumor growth prevention is still 91% compared with vehicle control mice. Inhibition of tumor growth remains prolonged and sustained up to 34 days post-treatment (day 67). On day 67, these mice are retreated with the same dose of this chemical for a second cycle (7 days) until day 74. Importantly, the antitumor effects are sustained after dosing is completed. [1] This compound leads to reduced expression of genes associated with angiogenesis in A549 xenograft model. In contrast, the RO4929097-resistant H460a xenograft displays little change in expression of these genes, underscoring the in vivo anti-angiogenesis mechanism of action of this agent.[2] For IL6 and IL8 overexpressing tumors, it no longer impacts angiogenesis or the infiltration of tumor associated fibroblasts. [4]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro potency assays
After RO4929097 is used, the Aβ peptides are measured by ECL assays using a variety of anti-Aβ antibodies and an Origen 1.5 Analyzer. The 4G8 murine mAb binds an epitope in the Aβ peptide (within amino acids 18–21) that is immediately distal to the α-secretase cleavage site. The G2–10 murine mAb binds the C terminus that is exposed after γ-secretase-mediated cleavage to generate amino acid 40 of the Aβ40 peptide. The FCA3542 rabbit antibody binds the C terminus that is exposed after γ-secretase-mediated cleavage to generate amino acid 42 of the Aβ42 peptide. The 4G8 mAb is biotinylated with biotin-LC-sulfo-N-hydroxysuccinimide-ester. The G2–10 and FCA3542 antibodies are ruthenylated with TAG-N-hydroxysuccinimide ester. Aβ(x-40) is detected with biotinylated 4G8 and ruthenylated G2–10. Aβ(x-42) is detected with biotinylated 4G8 and ruthenylated FCA3542.
細胞アッセイ 細胞株 WM35 and WM98.1 cell lines
濃度 10 μM
反応時間 DMSO
実験の流れ Primary melanoma cell lines, including WM35 and WM98.1, are seeded at 2.5 × 103 cells per well on a 12-well dish in triplicate. The day after (day 0), the medium is replaced, and DMSO or 10 μM RO4929097 is added and changed every 3-4 days. At the indicated time points, cells are fixed in 10% formalin solution and stored in PBS at 4 °C. At day 18-24, all the plates are stained with crystal violet. After color elution with 10% acetic acid, optical density is read at 590 nm.
動物実験 動物モデル Female nude mice bearing Calu-6 cells
投薬量 3 to 60 mg/kg
投与方法 Oral administration

参考

  • https://pubmed.ncbi.nlm.nih.gov/19773430/
  • https://pubmed.ncbi.nlm.nih.gov/22547109/
  • https://pubmed.ncbi.nlm.nih.gov/21980408/
  • https://pubmed.ncbi.nlm.nih.gov/21315665/
  • https://pubmed.ncbi.nlm.nih.gov/10801983/

カスタマーフィードバック

Data from [Stem Cells, 2014, 32(1), 301-12]

Data from [Stem Cells, 2014, 32(1), 301-12]

, 2012, Dr. Barbara Bedogni of Case Western Reserve University

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：

A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling [ Cell Death Dis, 2025, 16(1):150] PubMed: 40032820
Role of the Notch signaling pathway in porcine oocyte maturation [ Cell Commun Signal, 2025, 23(1):1] PubMed: 39748238
BMP, MEK, and WNT inhibition with NGN2 expression for rapid generation of hiPSC-derived neurons amenable to regional patterning [ Stem Cell Reports, 2025, 20(7):102539] PubMed: 40541177
Expression of genes involved in thyroid hormone action in human induced pluripotent stem cells during differentiation to insulin-producing cells: Effects of iopanoic acid on differentiation [ Mol Cell Endocrinol, 2025, 599:112490] PubMed: 39921130
Targeting endothelial PDGFR-β facilitates angiogenesis-associated bone formation through the PAK1/NICD axis [ J Cell Physiol, 2024, 10.1002/jcp.31291] PubMed: 38721633
Xenogenic Engraftment of Human-Induced Pluripotent Stem Cell-Derived Pancreatic Islet Cells in an Immunosuppressive Diabetic Göttingen Mini-Pig Model [ Cell Transplant, 2024, 33:9636897241288932] PubMed: 39401129
Novel Anti-B-cell Maturation Antigen Alpha-Amanitin Antibody-drug Conjugate HDP-101 Shows Superior Activity to Belantamab Mafodotin and Enhanced Efficacy in Deletion 17p Myeloma Models [ Res Sq, 2024, rs.3.rs-3843028] PubMed: 38260385
A precision oncology-focused deep learning framework for personalized selection of cancer therapy [ bioRxiv, 2024, 2024.12.12.628190] PubMed: 39763776
MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling [ Nat Commun, 2023, 14(1):6190] PubMed: 37794006

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。