GMX1778

製品コードS8117 バッチS811701

印刷

化学情報

Chemical Structure Synonyms CHS828 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H22ClN5O
分子量 371.86 CAS No. 200484-11-3
Solubility (25°C)* 体外 DMSO 74 mg/mL (198.99 mM)
Water Insoluble
Ethanol 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 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。

 3.700mg/ml (9.95mM) Taking the 1 mL working solution as an example, add 50 μL of 74 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.
Clear solution
5% DMSO 95% Corn oil

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。

 0.520mg/ml (1.40mM) Taking the 1 mL working solution as an example, add 50 μL of 10.4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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 GMX1778は、ニコチンアミドホスホリボシルトランスフェラーゼ（NAMPT）の強力かつ特異的な阻害剤であり、IC50およびKdはそれぞれ25 nM未満および120 nMです。GMX1778は、アポトーシスを特徴とするプログラム細胞死を誘発します。フェーズ1。
in vitro

GMX1778 induces NAD+ depletion through inhibition of NAD+ biosynthesis, followed by ATP depletion and ultimately resulted in cell death. This compound induces programmed cell death with apoptotic features. It suppresses nuclear factor-kappa B activity in cancer cells through downregulation of IKK activity (IC50=8 nM).

in vivo

GMX1778 (250 mg/kg, p.o.) shows marked antitumoural activity against three different human neuroendocrine tumours, midgut carcinoid (GOT1), pancreatic carcinoid (BON), and medullary thyroid carcinoma (GOT2), transplanted in nude mice.

プロトコル(参考用のみ)

キナーゼアッセイ In vitro coupled-enzyme NAMPT assay
Recombinant NAMPT activity is assessed using a coupled-enzyme assay based on the quantitation of NAD+. Reactions are performed at room temperature for 180 min using mixtures consisting of 50 mM HEPES (pH 7.4), 50 mM KCl, 5 mM MgCl2, 0.5 mM β-mercaptoethanol, 0.005% bovine serum albumin, 1% DMSO, 2.0 U/ml lactate dehydrogenase, 4 mM sodium L-lactate, 0.4 U/ml diaphorase, 6 μΜ resazurin sodium salt, 0.4 mM PRPP, 3.0 nM NMNAT1, 125 μM ATP, 50 μM NM, and 2 to 5 μM recombinant NAMPT. Fluorescence s measured with a Tecan Safire plate reader (excitation wavelength, 560 nm; emission wavelength, 590 nm). Ki values are calculated using Graphpad Prism 4.0 software and the Cheng-Prusoff equation.
細胞アッセイ 細胞株 HeLa cells
濃度 ~100 nM
反応時間 72 h
実験の流れ

Serial dilutions of GMX1778 in DMSO are performed to achieve a final concentration of 0.2% DMSO. Relative ATP levels after 72 h are determined using a ViaLight HS high-sensitivity cytotoxicity and cell proliferation BioAssay kit per the manufacturer's instructions. For this compound cytotoxicity rescue experiments, cells are treated with NA (10 μM)  simultaneously with this chemical. Sigmoidal dose-response curves are generated by nonlinear regression analysis of variable slope using GraphPad Prism version 4.00 (GraphPad Software) to calculate 50% inhibitory (IC50) values.
動物実験 動物モデル Nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors
投薬量 ~250 mg/kg
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/19703994/
  • https://pubmed.ncbi.nlm.nih.gov/11205250/
  • https://pubmed.ncbi.nlm.nih.gov/15197771/
  • https://pubmed.ncbi.nlm.nih.gov/16508338/

カスタマーフィードバック

Data from [Data independently produced by , , Signal Transduction and Targeted Therapy. 2017, volume 2, Article number: 17017.]

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 skin organoid-based infection platform identifies an inhibitor specific for HFMD [ Nat Commun, 2025, 16(1):2513] PubMed: 40082449
Heterogeneous therapy-resistant cancer cells have distinct and exploitable drug sensitivity profiles [ bioRxiv, 2025, 2025.04.25.650475] PubMed: 40654745
NAD+ regulates nucleotide metabolism and genomic DNA replication [ Nat Cell Biol, 2023, 10.1038/s41556-023-01280-z] PubMed: 37957325
Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options [ Cancers (Basel), 2023, 15(5)1415] PubMed: 36900207
Combined Targeting of NAD Biosynthesis and the NAD-dependent Transcription Factor C-terminal Binding Protein as a Promising Novel Therapy for Pancreatic Cancer [ Cancer Res Commun, 2023, 10.1158/2767-9764.CRC-22-0521] PubMed: 37707363
Combined Targeting of NAD Biosynthesis and the NAD-dependent Transcription Factor C-terminal Binding Protein as a Promising Novel Therapy for Pancreatic Cancer [ Cancer Res Commun, 2023, 3(10):2003-2013] PubMed: 37707363
NAMPT Inhibition Suppresses Cancer Stem-like Cells Associated with Therapy-Induced Senescence in Ovarian Cancer. [ Cancer Res, 2020, 80(4):890-900] PubMed: 31857293
Overexpression of the histidine triad nucleotide-binding protein 2 protects cardiac function in the adult mice after acute myocardial infarction. [ Acta Physiol (Oxf), 2020, 10.1111/apha.13439] PubMed: 31900976
Nicotinamide adenine dinucleotide replenishment rescues colon degeneration in aged mice. [ Signal Transduct Target Ther, 2017, 2:17017] PubMed: 29263919

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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