Pirfenidone

Pirfenidone is an anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II. Pirfenidone has well-established antifibrotic and anti-inflammatory properties in various in vitro systems and animal models of fibrosis. A number of cell-based studies have shown that pirfenidone reduces fibroblast proliferation, inhibits TGF-β stimulated collagen production and reduces the production of fibrogenic mediators such as TGF-β.

Product information

CAS Number: 53179-13-8

Molecular Weight: 185.22

Formula: C12H11NO

Synonym:

AMR69

Pirespa

Pirfenex

Etuary

brand name

Chemical Name: 5-methyl-1-phenyl-2-(1H)-pyridone

Smiles: CC1=CN(C(=O)C=C1)C1C=CC=CC=1

InChiKey: ISWRGOKTTBVCFA-UHFFFAOYSA-N

InChi: InChI=1S/C12H11NO/c1-10-7-8-12(14)13(9-10)11-5-3-2-4-6-11/h2-9H,1H3

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Pirfenidone (PFD) reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-β target gene and furin substrate involved in carcinogenesis. These data define PFD or PFD-related agents as promising agents for human cancers associated with enhanced TGF-β activity. In RAW264.7 cells, a murine macrophage-like cell line, Pirfenidone suppresses the proinflammatory cytokine TNF-α by a translational mechanism, which is independent of activation of the MAPK2, p38 MAPK, and JNK. In the murine endotoxin shock model, Pirfenidone potently inhibits the production of the proinflammatory cytokines, TNF-α, interferon-γ, and interleukin-6, but enhances the production of the anti-inflammatory cytokine, interleukin-10. Pirfenidone (PFD) shows its inhibitory effects on the proliferation of HLECs. Cell proliferation is attenuated in the 0.3 mg/mL group after 24 hours compare with the control group (P=0.044). The effect is more apparent in the 0.5 mg/mL group at 24, 48, and 72 hours (P<0.05). The proliferation is almost completely inhibited with 1 mg/mL PFD at all the time-points (P<0.01).

In Vivo:

Administration of Pirfenidone (300 mg/kg/day) for 4 wk. Pirfenidone significantly attenuates the score when administered in Bleomycin (BLM)-treated mice (P<0.0001). Moreover, collagen content is quantified in the lungs to evaluate the anti-fibrotic effects of Pirfenidone. The collagen content in the lungs of BLM-treated mice is significantly increased compared with that in saline- or Pirfenidone-treated mice, and this increase is significantly attenuated by Pirfenidone administration on day 28 after BLM treatment (P=0.0012).

References:

1. Cottin V, Maher T. Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. Eur Respir Rev. 2015 Mar;24(135):58-64. doi: 10.1183/09059180.00011514. Review. PubMed PMID: 25726556.
2. Poletti V, Ravaglia C, Tomassetti S. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Rev Respir Med. 2014 Oct;8(5):539-45. doi: 10.1586/17476348.2014.915750. Epub 2014 Aug 12. Review. PubMed PMID: 25113033.
3. Takeda Y, Tsujino K, Kijima T, Kumanogoh A. Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis. Patient Prefer Adherence. 2014 Mar 21;8:361-70. doi: 10.2147/PPA.S37233. eCollection 2014. Review. PubMed PMID: 24711695; PubMed Central PMCID: PMC3968083.
4. Kreuter M. Pirfenidone: an update on clinical trial data and insights from everyday practice. Eur Respir Rev. 2014 Mar 1;23(131):111-7. doi: 10.1183/09059180.00008513. Review. PubMed PMID: 24591668.
5. Xaubet A, Serrano-Mollar A, Ancochea J. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Opin Pharmacother. 2014 Feb;15(2):275-81. doi: 10.1517/14656566.2014.867328. Epub 2013 Dec 6. Review. PubMed PMID: 24308635.

Products are for research use only. Not for human use.