RGFP966 (Synonyms: RGFP 966;RGFP-966) |
| カタログ番号GC14285 |
RGFP966はN-(o-アミノフェニル)カルボキサミド系HDAC阻害剤で、HDAC3に対するIC50は0.08μMである。これは、HDAC3を標的とする、スローオン/スローオフ競合タイト結合阻害剤の一種である。
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Cas No.: 1357389-11-7
Sample solution is provided at 25 µL, 10mM.
RGFP966はN-(o-アミノフェニル)カルボキサミド系HDAC阻害剤で、HDAC3に対するIC50は0.08μMである。これは、HDAC3を標的とする、スローオン/スローオフ競合タイト結合阻害剤の一種である。RGFP966は、様々な炎症性疾患において炎症反応を抑制することが証明されている[1-3]。
RGFP966（1μM、20時間）は、LPS/IFNγ刺激を受けたRAW264.7マクロファージにおける炎症性遺伝子の発現を減弱させる[3]。RGFP966（10-25μM；48時間）はHCC細胞の増殖と遊走の両方を阻害した[4]。
RGFP966（10mg/kg；SBIの6時間前）はHDAC3の上方制御を阻害し、外科的脳損傷（SBI）ラットの損傷領域周辺の神経細胞を保護した[5]。RGFP966(10mg/kg/日;i.p;5日間)は、LPS誘発マウスの抑うつ様行動を改善した。RGFP966処理は、toll-like receptor 4（TLR4）、nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 （NLRP3）、カスパーゼ-1、およびinterleukin-1β（IL-1β）の発現レベルをダウンレギュレートした［6］。RGFP966（10mg/kgまたは20mg/kg）はHDAC3の発現およびHDAC3活性を低下させ、そして好酸球と肥満細胞の動員、杯細胞の増殖、炎症性サイトカインのレベルが減少する。その結果、アレルギー性鼻炎（AR）マウスにおけるアレルギー反応と炎症反応が緩和された[7]。
References:
[1]. Malvaez M, McQuown SC, et,al. HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2647-52. doi: 10.1073/pnas.1213364110. Epub 2013 Jan 7. PMID: 23297220; PMCID: PMC3574934.
[2]. Chou CJ, Herman D, et,al. Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases. J Biol Chem. 2008 Dec 19;283(51):35402-9. doi: 10.1074/jbc.M807045200. Epub 2008 Oct 24. PMID: 18953021; PMCID: PMC2602898.
[3]. Leus NG, van der Wouden PE, et,al. HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF-κB p65 transcriptional activity. Biochem Pharmacol. 2016 May 15;108:58-74. doi: 10.1016/j.bcp.2016.03.010. Epub 2016 Mar 16. PMID: 26993378; PMCID: PMC4844503.
[4]. Yu X, Yang F, et,al. RGFP966 Suppresses Tumor Growth and Migration Through Inhibition of EGFR Expression in Hepatocellular Carcinoma Cells in vitro. Drug Des Devel Ther. 2020 Jan 10;14:121-128. doi: 10.2147/DDDT.S234871. PMID: 32021097; PMCID: PMC6959505.
[5]. Gu HP, Wu XF, et,al. RGFP966 exerts neuroprotective effect via HDAC3/Nrf2 pathway after surgical brain injury in rats. Heliyon. 2023 Jul 12;9(7):e18160. doi: 10.1016/j.heliyon.2023.e18160. PMID: 37539293; PMCID: PMC10395478.
[6]. Bian HT, Xiao L, et,al. RGFP966 is protective against lipopolysaccharide-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. Int Immunopharmacol. 2021 Dec;101(Pt B):108259. doi: 10.1016/j.intimp.2021.108259. Epub 2021 Oct 16. PMID: 34666303.
[7]. Zhang W, Sun X, et,al. RGFP966, a selective HDAC3 inhibitor, ameliorates allergic and inflammatory responses in an OVA-induced allergic rhinitis mouse model. Int Immunopharmacol. 2021 Apr;93:107400. doi: 10.1016/j.intimp.2021.107400. Epub 2021 Jan 30. PMID: 33529911.
| 細胞実験[1]: | |
細胞株 | マウスRAW 264.7マクロファージ |
準備方法 | 細胞を1μM RGFP966で20時間インキュベートし、最後の4時間LPS/IFNγで刺激した。 |
反応条件 | 1μM;20時間 |
アプリケーション | RGFP966、刺激したLPS/IFNγ RAW 264.7マクロファージにおける炎症性遺伝子発現を減弱させる。 |
| 動物実験 [2]: | |
動物モデル | 成体雄C57BL/6Jマウス(体重20–22g) |
準備方法 | マウスを対照群、LPS群、LPS+RGFP966群、RGFP966群の4群に分けた。LPSはリン酸緩衝生理食塩水(PBS)に可溶化され、腹腔内(i.p.)に1 mg/kg/日の投与量で合計5回の注射で注入された。RGFP966をジメチルスルホキシド(DMSO)、PEG300、生理食塩水で希釈した後、10mg/kg/dayの用量で合計5回注射した。 |
投与形態 | 10 mg/kg/日; i.p;5日間 |
アプリケーション | RGFP966治療により、マウスのLPS誘発性体重変化が逆転した。 |
参考文献: | |
| Cas No. | 1357389-11-7 | SDF | |
| 同義語 | RGFP 966;RGFP-966 | ||
| Canonical SMILES | C1=CC=C(C=C1)C=CCN2C=C(C=N2)C=CC(=O)NC3=C(C=C(C=C3)F)N | ||
| Formula | C21H19FN4O | M.Wt | 362.4 |
| 溶解度 | ≥ 18.12mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.7594 mL | 13.7969 mL | 27.5938 mL |
| 5 mM | 0.5519 mL | 2.7594 mL | 5.5188 mL |
| 10 mM | 0.2759 mL | 1.3797 mL | 2.7594 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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