Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production. Pirfenidone inhibits fibroblast, epidermal, platelet-derived, and transforming beta-1 growth factors, thereby slowing tumor cell proliferation. This agent also inhibits DNA synthesis and the production of mRNA for collagen types I and III, resulting in a reduction in radiation-induced fibrosis.

0.5% Pirfenidone流食处理可以降低大鼠肝损伤程度,这与肝星状细胞增殖及胶原沉积降低有关.0.5% Pirfenidone流食处理可以使大鼠二甲基亚硝胺诱导的原骨胶原α1(I), TIMP-1 和 MMP-2转录水平下调 50-60%.在小鼠中,Pirfenidone（250 mg/kg）明显抑制促炎细胞因子的产生包括TNF-α,INF-γ和IL-6,但会促进抗炎细胞因子产生,如IL-10.在接受低盐饮食的Sprague-Dawley大鼠中,Pirfenidone（250 mg/kg/day）可改善约50%的环孢素诱导的纤维化并使TGF-β1蛋白表达下降80%.在每天静脉注射bleomycin后肺纤维化的ICR小鼠中,Pirfenidone（400 mg/kg）对热休克蛋白47阳性细胞和肌成纤维细胞具有抑制作用,这些细胞是造成细胞外基质积聚的主要细胞.

在CCL-64细胞中,Pirfenidone（< 5 mM）通过影响TGF-β2 mRNA的表达和pro-TGF-β过程进而降低TGF-β生物活性。在LN-308细胞中,Pirfenidone（< 8.3 mM）对重组弗林蛋白酶活性及MMP-11表达均有剂量依赖性的抑制效果。在LN-18,T98 g,LNT-229和LN-308细胞系中,Pirfenidone（<10 mM）浓度依赖性地使胶质瘤细胞密度降低并具有。在RAW264.7细胞中,Pirfenidone（< 300 μg/mL）通过翻译机制抑制TNF-α ,该过程与促分裂原活化蛋白激酶2,p38MAP激酶及JNK的激活无关。

Pirfenidone (PFD) is dissolved in DMSO and stored, and then diluted with appropriate media before use[3]. HLECs are seeded in 96-well plates (1×104 cells/well) for 24 hours in α-MEM/10% FBS/1%NEAA, and are cultured in stationary tubes in serum-free medium for 24 hours. And then the culture medium is removed and cells are bathed in α-MEM with 10% FBS and 1% NEAA supplemented with 0, 0.01, 0.1, 0.2, 0.3, 0.5, or 1 mg/mL Pirfenidone for 0, 4, 12, 24, 48, or 72 hours. After incubation with 180 μL α-MEM and 20 μL of 5 mg/mL MTT for 4 hours at 37°C, the MTT solution is discarded. The Formosan precipitates are dissolved in 180 μL DMSO by agitating the dishes for 10 minutes at 200 rpm on an orbital shaker. The absorbance at 490 nm in each well is read with a micro plate reader. We further examined the effects of PFD by refining the concentrations at 0.2, 0.25, 0.3, 0.4, 0.5 and 0.6 mg/mL using the MTT assay[3].

53179-13-8

C12H11NO

185.226

S-7701,AMR-69;AMR69;吡非尼酮;S-7701;Pirfenidone

[1]Kakugawa T, et al. Eur Respir J, 2004, 24(1), 57-65. [2]Di Sario A, et al. Dig Liver Dis, 2004, 36(11), 744-751. [3]Burghardt I, et al. Biochem Biophys Res Commun, 2007, 354(2), 542-547. [4]Nakazato H, et al. Eur J Pharmacol, 2002, 446(1-3), 177-185. [5]Shihab FS, et al. Am J Transplant, 2002, 2(2), 111-119.

[1]Hong M J, Hao M J, Zhang G Y, et al. Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus Exophiala oligosperma MCCC 3A01264. Marine Drugs. 2022, 20(7): 448

DMSO:199.8 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years