Cl-amidine

製品コードS8141 バッチS814102

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

C14H19ClN4O2.C2HF3O2
分子量 424.8 CAS No. 1043444-18-3
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 85 mg/mL (200.09 mM)
Water (warmed with 50ºC water bath) 43 mg/mL (101.22 mM)
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。

 4.250mg/ml (10.00mM) Taking the 1 mL working solution as an example, add 50 μL of 85 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 Cl-amidine is an irreversible pan-peptidylarginine deiminase (PAD) inhibitor with IC50 values of 5.9 ± 0.3 μM, 0.8 ± 0.3 μM, 6.2 ± 1.0 μM for PAD4, PAD1 and PAD3, respectively. Cl-amidine induces apoptosis.
in vitro Cl-amidine antagonizes the PAD4-mediated enhancement of the the p300GBD-GRIP1 interaction in a dose-dependent manner. The inhibitory effect of this compound is not a nonspecific one but is targeted at the active PAD4 enzyme[1]. This compound increases p53 expression in CD45 positive immune cells. It triggers the differentiation and apoptosis of multiple cancer cell lines that are p53+/+ and p53−/− (e.g., HL60, HT29, TK6, and U2-OS cells). This chemical induces the expression of p53 and several downstream target genes including the cyclin dependent kinase inhibitor p21, GADD45, and the proapoptotic protein PUMA in U2-OS osteosarcoma cells[2].
in vivo Cl-amidine treatment inhibits NZM(New Zealand mixed 2328) NET(neutrophil extracellular trap) formation in vivo and significantly alters circulating autoantibody profiles and complement levels while reducing glomerular IgG deposition. Further, this compound increases the differentiation capacity of bone marrow endothelial progenitor cells, improves endothelium-dependent vasorelaxation, and markedly delays time to arterial thrombosis induced by photochemical injury. It delays thrombosis development in NZM mice. This chemical inhibits PADs in mice without significant toxicity and improves disease phenotypes in animal models of inflammatory arthritis and inflammatory bowel disease[3]. And it is shown to reduce disease severity in mouse models of ulcerative colitis and RA[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 CV-1 cells
濃度 0-200 μM
反応時間 40 h
実験の流れ

CV-1 cells are transiently transfected with plasmids encoding a luciferase reporter construct, p300GBD fused to the Gal4 DNA binding domain, the p300 binding domain of GRIP1 (i.e., the AD1 domain) fused to the VP16 activation domain (AD), and either wild-type PAD4 or the catalytically defective C645S mutant. Cl-amidine (0-200 μM) is then added to the cell culture medium and incubated for 40 h. Cell extracts are then prepared, and the luciferase activity present in these extracts is quantified. 
動物実験 動物モデル DSS mouse model of colitis (genetic background：C57BL/6 mice)
投薬量 75 mg/kg (i.p); 5, 25, and 75 mg/kg(oral)
投与方法 by oral gavage or i.p

参考

  • https://pubmed.ncbi.nlm.nih.gov/17002273/
  • https://pubmed.ncbi.nlm.nih.gov/20469888/
  • https://pubmed.ncbi.nlm.nih.gov/23722903/
  • https://pubmed.ncbi.nlm.nih.gov/21415415/

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 bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination [ Immunity, 2025, S1074-7613(25)00069-X] PubMed: 40015270
NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression [ Cell Rep, 2025, 44(2):115226] PubMed: 39827463
Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion [ Nat Commun, 2024, 15(1):8663] PubMed: 39375351
Role of Peptidyl arginine deiminase 4-dependent macrophage extracellular traps formation on Type 1 Diabetes pathogenesis [ Diabetes, 2024, db231000] PubMed: 39137121
Moxibustion-mediated alleviation of synovitis in rats with rheumatoid arthritis through the regulation of NLRP3 inflammasome by modulating neutrophil extracellular traps [ Heliyon, 2024, 10(1):e23633] PubMed: 38187290
Medical ozone alleviates acute lung injury by enhancing phagocytosis targeting NETs via AMPK/SR-A1 axis [ J Biomed Res, 2024, 1-16.] PubMed: 38807426
Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis [ Cell Discov, 2023, 9(1):104] PubMed: 37848438
Metformin potentiates nephrotoxicity by promoting NETosis in response to renal ferroptosis [ Cell Discov, 2023, 9(1):104] PubMed: 37848438
Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathy [ EBioMedicine, 2023, 90:104499] PubMed: 36870200
Fasting-mimicking diet alleviates inflammatory pain by inhibiting neutrophil extracellular traps formation and neuroinflammation in the spinal cord [ Cell Commun Signal, 2023, 21(1):250] PubMed: 37735678

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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