RGFP966 is an N-(o-aminophenyl) carboxamide HDAC inhibitor with an IC50 of 0.08 μM for HDAC3, It is a class of slow on/slow off competitive tight binding inhibitors targeting HDAC3. RGFP966 has been demonstrated to suppress inflammatory responses in various inflammatory diseases [1-3].
RGFP966(1μM ;20 h) attenuates the inflammatory gene expression in LPS/IFNγ-stimulated RAW 264.7 macrophage[3]. RGFP966(10-25μM;48h) inhibited both proliferation and migration of HCC cells[4].
RGFP966(10 mg/kg;6h before SBI) inhibited the upregulation of HDAC3 and saved the nerve cells around the damaged area in surgical brain injury (SBI) rats[5]. RGFP966(10 mg/kg/day;i.p; 5days) could improve the LPS-induced depressive-like behaviors in mice. RGFP966 treatment downregulated the expression levels of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-1β (IL-1β) [6]. RGFP966(10 mg/kg or 20 mg/kg) reduce HDAC3 expression and HDAC3 activities, and then eosinophils and mast cells recruitment, goblet cells proliferation and inflammatory cytokines levels are decreased, resulting in the alleviation of allergic and inflammatory responses in allergic rhinitis (AR) mice [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.
RGFP966是一种N-(o-aminophenyl)carboxamide HDAC抑制剂，对HDAC3的IC50为0.08 μM，是一类针对HDAC3的慢开/慢关竞争性紧密结合抑制剂。RGFP966已被证明可以抑制各种炎症性疾病的炎症反应[1-3]。
RGFP966 (1μM ;20 h)可减弱LPS/IFNγ刺激的RAW 264.7巨噬细胞中炎症基因的表达[3]。RGFP966 (10-25μM;48h)对HCC细胞的增殖和迁移均有抑制作用[4]。
RGFP966 (10 mg/kg;6h before SBI)抑制HDAC3的上调，挽救了SBI大鼠损伤区周围的神经细胞[5]。RGFP966 (10 mg/kg/day;i.p; 5days)可改善LPS诱导的小鼠抑郁样行为。RGFP966处理下调toll样受体4 (TLR4)、核苷酸结合寡聚化结构域样受体pyrin domain-containing-3 (NLRP3)、caspase-1和白细胞介素-1β (IL-1β)的表达水平[6]。RGFP966 (10 mg/kg or 20 mg/kg)降低HDAC3的表达和活性，从而降低嗜酸性粒细胞和肥大细胞募集、杯状细胞增殖和炎症因子水平，从而减轻变应性鼻炎(AR)小鼠的过敏和炎症反应[7]。