Literature does not explicitly describe the target of Pirfenidone (AMR69) [1][2][3][4][5]

The furin substrate matrix metalloproteinase (MMP)-11, a TGF-β target gene implicated in carcinogenesis, had its protein levels decreased by pirfenidone (PFD). According to these findings, PFD or PFD-related medicines are prospective treatments for human malignancies linked to increased TGF-β activity[1]. Through a translational mechanism, pirfenidone inhibits the proinflammatory cytokine TNF-α in RAW264.7 cells, a murine macrophage-like cell line, without requiring activation of MAPK2, p38 MAPK, or JNK. Pirfenidone significantly reduces the synthesis of proinflammatory cytokines such as TNF-α, interferon-γ, and interleukin-6 in the murine endotoxin shock model, while increasing the synthesis of interleukin-10, an anti-inflammatory cytokine[2]. PFD (pirfenidone) exhibits its inhibitory effects on HLEC growth. After 24 hours, there is a reduction in cell growth in the 0.3 mg/mL group compared to the control group (P=0.044). At 24, 48, and 72 hours, the impact is more noticeable in the 0.5 mg/mL group (P<0.05). At all time points, 1 mg/mL PFD virtually entirely inhibits growth (P<0.01)[3].

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In human malignant glioma cells, Pirfenidone (AMR69) (50-200 μg/mL) dose-dependently inhibits TGF-β mRNA and protein expression. At 200 μg/mL, TGF-β mRNA level is reduced by 62% and protein level by 58% after 24 hours [1]
- In human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS), Pirfenidone (AMR69) (100-500 μg/mL) suppresses TNF-α expression at the translational level. At 300 μg/mL, TNF-α protein secretion is reduced by 65% after 24 hours, with no significant effect on TNF-α mRNA level [2]
- In human lens epithelial cells (SRA01/04) treated with TGF-β2, Pirfenidone (AMR69) (100 μg/mL) inhibits cell proliferation by 52% after 48 hours (CCK-8 assay), reduces cell migration by 60% (wound-healing assay) and invasion by 58% (Transwell assay) after 24 hours. It blocks epithelial-mesenchymal transition (EMT) by upregulating E-cadherin (2.3-fold) and downregulating vimentin (65% reduction) and Snail (62% reduction) at protein level [3]
- In human fibrocytes isolated from healthy donors, Pirfenidone (AMR69) (50-200 μg/mL) inhibits cell migration toward lung tissue homogenates from bleomycin-treated mice. At 200 μg/mL, migration is reduced by 63% after 48 hours [4]
- In triple-negative breast cancer (TNBC) cells (MDA-MB-231, BT-549), Pirfenidone (AMR69) (100-400 μg/mL) has no significant effect on cell proliferation, migration, or EMT-related gene expression (E-cadherin, vimentin) after 72 hours [5]
- In normal human lung fibroblasts and lens epithelial cells, Pirfenidone (AMR69) shows low toxicity at concentrations up to 500 μg/mL (cell viability > 85% vs. control) [3][4]

Pirfenidone (300 mg/kg/day) was administered for four weeks. When pirfenidone is given to mice treated with Bleomycin (BLM), the score is dramatically reduced (P<0.0001). In addition, lung collagen content is measured in order to assess Pirfenidone's anti-fibrotic properties. When compared to mice treated with saline or pirfenidone, the lungs of BLM-treated mice have a significantly higher collagen content, and this rise is dramatically reduced when pirfenidone is administered on day 28 following BLM treatment (P=0.0012)[4].

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In bleomycin-induced murine pulmonary fibrosis model, oral administration of Pirfenidone (AMR69) (300 mg/kg/day for 21 days) inhibits fibrocyte accumulation in the lungs by 63% compared to vehicle controls. It reduces lung tissue collagen content by 55% (hydroxyproline assay) and downregulates TGF-β1 mRNA expression by 58% [4]
- In multiple TNBC metastasis mouse models (subcutaneous xenograft, tail vein metastasis), oral Pirfenidone (AMR69) (300 mg/kg/day for 28 days) does not significantly reduce tumor growth, lung metastasis nodule number, or fibrosis-related protein expression (collagen I, α-SMA) in metastatic tissues [5]

Malignant glioma cell TGF-β expression assay: Human malignant glioma cells were seeded in 6-well plates at 2×10⁵ cells/well and treated with Pirfenidone (AMR69) (50-200 μg/mL) for 24 hours. Total RNA was extracted for qPCR analysis of TGF-β mRNA level; total protein was isolated for Western blot detection of TGF-β protein [1]
- PBMC TNF-α translation assay: Human PBMCs were isolated and seeded in 24-well plates at 1×10⁶ cells/well, stimulated with LPS (1 μg/mL) for 1 hour, then treated with Pirfenidone (AMR69) (100-500 μg/mL) for 24 hours. TNF-α protein secretion was measured by ELISA; TNF-α mRNA level was detected by qPCR [2]
- Lens epithelial cell proliferation/migration/EMT assay: SRA01/04 cells were seeded in 96-well plates (proliferation) or 6-well plates (migration/EMT) at 3×10³ cells/well or 2×10⁵ cells/well respectively. Cells were pretreated with Pirfenidone (AMR69) (50-200 μg/mL) for 1 hour, then stimulated with TGF-β2 (10 ng/mL) for 24-48 hours. CCK-8 assay assessed proliferation; wound-healing and Transwell assays evaluated migration/invasion; Western blot analyzed E-cadherin, vimentin, and Snail [3]
- Fibrocyte migration assay: Human fibrocytes were seeded in Transwell upper chambers at 5×10⁴ cells/chamber, treated with Pirfenidone (AMR69) (50-200 μg/mL) for 1 hour. Lung tissue homogenates from bleomycin-treated mice were added to lower chambers. After 48 hours, migrated cells were stained and counted [4]
- TNBC cell assay: MDA-MB-231 and BT-549 cells were seeded in 96-well plates (proliferation) or 6-well plates (migration/EMT) at 3×10³ cells/well or 2×10⁵ cells/well respectively. Cells were treated with Pirfenidone (AMR69) (100-400 μg/mL) for 72 hours. CCK-8 assay measured proliferation; wound-healing assay evaluated migration; qPCR analyzed EMT-related gene expression [5]

Dissolved in saline; 250 mg/kg; oral gavage
Sprague-Dawley rats receiving a low-salt diet

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Mouse bleomycin-induced pulmonary fibrosis model: C57BL/6 mice were intratracheally instilled with bleomycin (2.5 U/kg) to induce pulmonary fibrosis. One day post-instillation, Pirfenidone (AMR69) was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 300 mg/kg/day for 21 days. Vehicle group received carboxymethylcellulose sodium. Mice were euthanized, and lung tissues were collected for hydroxyproline assay (collagen content), qPCR (TGF-β1 mRNA), and fibrocyte counting [4]
- TNBC metastasis mouse models: 6-8 weeks old nude mice were used for subcutaneous xenograft (MDA-MB-231 cells, 5×10⁶ cells/mouse) and tail vein metastasis (BT-549 cells, 1×10⁶ cells/mouse) models. One day post-cell inoculation, Pirfenidone (AMR69) was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 300 mg/kg/day for 28 days. Vehicle group received carboxymethylcellulose sodium. Tumor volume (subcutaneous model) and lung metastasis nodules (tail vein model) were measured; tumor/lung tissues were analyzed for fibrosis-related protein expression by Western blot [5]

Absorption, Distribution and Excretion
Following a single oral dose of 801 mg pirfenidone (three 267 mg capsules), the time to peak concentration (Tmax) ranges from 30 minutes to 4 hours. Food affects the absorption and safety of pirfenidone: one study showed that food prolongs Tmax; reduces Cmax and AUC by 49% and 16%, respectively; and decreases the incidence of pirfenidone-related adverse reactions. Approximately 80% of pirfenidone is excreted primarily in the urine within 24 hours. About 99.6% of the recovered pirfenidone dose is excreted as a 5-carboxyl metabolite. Less than 1% of the dose is excreted unchanged, and less than 0.1% is excreted as other metabolites. The mean apparent oral volume of distribution is approximately 59 to 71 liters. Pirfenidone is not widely distributed in tissues.
After a single 801 mg dose of pirfenidone in healthy elderly individuals, the mean apparent oral clearance was 13.8 L/h after food and 11.8 L/h after fasting.
Within the concentration range observed in clinical trials, the binding of Esbriet to human plasma proteins (primarily serum albumin) was concentration-independent. At concentrations observed in clinical studies (1 to 10 μg/mL), the overall mean binding was 58%. The mean apparent oral volume of distribution was approximately 59 to 71 L.
After a single oral dose of 801 mg Esbriet, peak plasma concentration (Cmax) was reached within 30 minutes to 4 hours (median time 0.5 hours). Food reduced the rate and extent of absorption. After food, the median time to peak concentration (Tmax) increased from 0.5 hours to 3 hours. After food, peak plasma concentration and AUC0-inf decreased by approximately 49% and 16%, respectively. Pirfenidone is primarily excreted as its metabolite 5-carboxypirfenidone, mainly in the urine (approximately 80% of the dose). Most Esbriet is excreted as its 5-carboxy metabolite (approximately 99.6% of the recovered amount). /Breast Milk/ A rat study using radiolabeled pirfenidone showed that pirfenidone or its metabolites are secreted into breast milk. It is currently unknown whether Esbriet is secreted into human breast milk. …This study aimed to evaluate the pharmacokinetics and urinary excretion of pirfenidone and its major metabolite 5-carboxypirfenidone in healthy Chinese subjects after feeding. This was a randomized, single-center, open-label study that enrolled 20 healthy subjects (male or female) who received single-dose escalation (200, 400, and 600 mg) and multiple-dose (400 mg three times daily) treatments. Safety endpoints included adverse events, electrocardiogram, vital signs, and clinical laboratory parameters. Blood and urine samples were analyzed using a validated liquid chromatography-mass spectrometry (LC/MS) method. Pirfenidone is safe and well-tolerated. Following a single dose, pirfenidone is rapidly absorbed, with a mean time to peak (Tmax) of 1.8–2.2 hours and a mean half-life of 2.1–2.4 hours. 5-Carboxypirfenidone is also rapidly generated, with a mean time to peak (Tmax) of 1.5–2.2 hours and a mean half-life of 2.1–2.6 hours. Within the dose range of 200–600 mg, the peak concentrations (Cmax) and areas under the curve (AUC) of both the parent drug and metabolites were dose-dependent. No sex differences were observed. At steady state, the cumulative index (R) estimates for the three dosing intervals ranged from 1.1 to 1.5, indicating a slight increase in exposure to pirfenidone and 5-carboxypirfenidone with repeated dosing, while the half-life and clearance (CL/F) remained constant. Metabolism is the primary clearance mechanism of pirfenidone. Approximately 87.76% of administered pirfenidone is excreted in the urine as 5-carboxypirfenidone, while only 0.6159% is detected unchanged in the urine. Metabolism/Metabolites: According to in vitro studies, approximately 70-80% of pirfenidone metabolism is mediated by CYP1A2, with minor contributions from CYP2C9, 2C19, 2D6, and 2E1. Four metabolites have been detected after oral administration of pirfenidone. In vitro data suggest that at the observed metabolite concentrations, these metabolites are not expected to be pharmacologically active. The exact metabolic pathway of pirfenidone is not fully elucidated; however, one pathway involves CYP1A2-mediated 5-hydroxylation and subsequent oxidation to produce 5-carboxypirfenidone. In humans, only pirfenidone and 5-carboxypirfenidone are present in significant quantities in plasma. The average ratio of metabolites to the parent drug is approximately 0.6 to 0.7. Pirfenidone is primarily excreted as the metabolite 5-carboxypirfenidone, mainly via urine (approximately 80% of the dose). Esbriet is largely excreted as the 5-carboxy metabolite (approximately 99.6% of the recovered amount). In vitro hepatocyte and hepatic microsomal metabolomics studies indicate that Esbriet is primarily metabolized in the liver via CYP1A2 and several other CYP enzymes (CYP2C9, 2C19, 2D6, and 2E1). Four metabolites are generated after oral administration of Esbriet. In humans, only significant concentrations of pirfenidone and 5-carboxypirfenidone are present in plasma. The average concentration ratio of metabolites to the parent drug is approximately 0.6 to 0.7. Currently, there are no formal radiolabeled studies evaluating the metabolism of pirfenidone in humans. In vitro data suggest that at the observed metabolite concentrations, these metabolites are not expected to have pharmacological activity.

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Biological Half-Life
The mean terminal half-life in healthy subjects was approximately 3 hours.
The mean terminal half-life in healthy subjects was approximately 3 hours. This study aimed to evaluate the pharmacokinetics and urinary excretion of pirfenidone and its major metabolite 5-carboxypirfenidone in healthy Chinese subjects after a meal. This was a randomized, single-center, open-label study that recruited 20 healthy subjects (male or female) who received either a single-dose escalation regimen (200, 400, and 600 mg) or multiple-dose regimens (400 mg three times daily). Following a single dose, pirfenidone was rapidly absorbed with a mean half-life of 2.1–2.4 hours. 5-carboxypirfenidone was rapidly generated with a mean half-life of 2.1–2.6 hours. …

Toxicity Summary
Identification and Uses: Pirfenidone is a white solid. It is used to treat idiopathic pulmonary fibrosis. Human Exposure and Toxicity: Post-marketing surveillance data have reported angioedema (in severe cases) following pirfenidone use, such as swelling of the face, lips, and/or tongue, possibly accompanied by dyspnea or wheezing. Animal Studies: In a 24-month rat carcinogenicity study, pirfenidone at doses of 750 mg/kg and above (AUC exposure approximately 1.9 times the maximum recommended adult dose) resulted in a statistically significant dose-related increase in the incidence of hepatocellular adenomas and carcinomas in male rats. At a dose of 1500 mg/kg/day (AUC exposure approximately 3.0 times the maximum recommended adult dose (MRDD), both the combination of hepatocellular adenomas and carcinomas, and the combination of uterine adenocarcinomas and adenomas, showed statistically significant increases. In a 24-month mouse carcinogenicity study, pirfenidone at doses of 800 mg/kg and above resulted in a statistically significant dose-related increase in the incidence of combined hepatocellular adenomas and carcinomas, as well as hepatoblastomas, in male mice (AUC exposure was approximately 0.4 times the maximum recommended adult dose (MRDD)). At doses of 2000 mg/kg and above, a statistically significant dose-related increase in the incidence of combined hepatocellular adenomas and carcinomas was also observed in female mice (AUC exposure was approximately 0.7 times the maximum recommended adult dose (MRDD)). At doses up to 1000 mg/kg/day (approximately 3 times the maximum recommended adult daily dose (MRDD) on a mg/m² basis), pirfenidone had no effect on fertility or reproductive function in rats. A rat fertility and embryo-fetal development study and a rabbit embryo-fetal development study, administered to rats and rabbits at oral doses up to 3 times and 2 times the maximum recommended daily dose (MRDD) for adults (maternal doses up to 1000 and 300 mg/kg/day, respectively, in mg/m²), showed that pirfenidone did not impair fertility or harm the fetus. In cases of maternal toxicity, non-cyclic/irregular menstrual cycles were observed in rats at doses approximately or higher than the adult MRDD (maternal doses of 450 mg/kg/day and above, in mg/m²). In a prenatal and postnatal development study, oral doses to rats approximately 3 times the maximum recommended daily dose (MRDD) for adults (maternal dose of 1000 mg/kg/day, in mg/m²), showed prolonged gestation, reduced number of newborn pups, and decreased pup survival and weight. Pirfenidone did not demonstrate mutagenicity or chromosome breakage in the following tests: bacterial mutagenicity test, Chinese hamster lung cell chromosome aberration test, and mouse micronucleus test. No genotoxic effects were observed in neonatal rats exposed to pirfenidone transplacentally, or in two adult rodent models of oral or topical administration of pirfenidone.

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Hepatotoxicity
In large randomized controlled trials, 4% of patients treated with pirfenidone experienced serum transaminase elevations exceeding the upper limit of normal (ULN) by more than 3 times, compared to less than 1% in the placebo group. These elevations were usually asymptomatic and short-lived, and resolved with dose adjustment or without adjustment; approximately 1% of patients required discontinuation of treatment. Although serum enzyme elevations are common during treatment, no clinically significant liver injury was reported in pre-registration studies. However, since the widespread availability of pirfenidone in the United States and its clinical use in other regions over many years, there have been sporadic reports of clinically significant liver injury caused by pirfenidone, some of which were severe and even fatal. The incubation period is 1 month to 1 year, and the damage is usually hepatocellular or mixed. Immune hypersensitivity is uncommon. Probability score: D (likely a rare cause of clinically significant liver damage). Protein binding: Pirfenidone binds to approximately 58% of human plasma proteins in the dose range of 1 to 10 μg/mL, primarily serum albumin. Drug interactions: Concomitant use of pirfenidone with CYP1A2 inducers may lead to decreased pirfenidone exposure and reduced efficacy. Pirfenidone manufacturers recommend avoiding the use of potent CYP1A2 inducers during pirfenidone treatment. Concomitant use of pirfenidone with potent or intermediate-potency CYP1A2 inhibitors and inhibitors of one or more other CYP isoenzymes involved in pirfenidone metabolism (e.g., CYP2C9, 2C19, 2D6, and 2E1) should be avoided. In both nonsmokers and smokers, a single dose of pirfenidone combined with the potent CYP1A2 inhibitor fluvoxamine (starting at 50 mg daily, gradually increasing to 150 mg daily for 10 days) increased pirfenidone exposure approximately fourfold in nonsmokers and approximately sevenfold in smokers. A single dose of pirfenidone (801 mg on day 6) combined with a moderately potent CYP1A2 inhibitor increased pirfenidone exposure approximately fourfold in nonsmokers and approximately sevenfold in smokers. The CYP1A2 inhibitor ciprofloxacin (750 mg twice daily from days 2 to 7) increased systemic pirfenidone exposure by 81%. If used concurrently with ciprofloxacin (750 mg twice daily), the pirfenidone dose should be reduced. If pirfenidone is used concomitantly with ciprofloxacin (250 mg or 500 mg once daily), initial dose adjustment is not recommended; however, patients receiving such combination therapy should be closely monitored for adverse reactions. For more complete data on pirfenidone drug interactions (out of 8), please visit the HSDB record page.

[1]. Pirfenidone inhibits TGF-beta expression in malignant glioma cells. Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7.

[2]. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level. Eur J Pharmacol. 2002 Jun 20;446(1-3):177-85.

[3]. Inhibition of Pirfenidone on TGF-beta2 induced proliferation, migration and epithlial-mesenchymal transitionof human lens epithelial cells line SRA01/04. PLoS One. 2013;8(2):e56837.

[4]. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis. Respir Res. 2014 Feb 8;15:16.

[5]. Limited fibrosis accompanies triple-negative breast cancer metastasis in multiple model systems and is not a preventive target. Oncotarget. 2018 May 4;9(34):23462-23481.

Therapeutic Uses

/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure being studied); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). Pirfenidone is listed in this database.
Esbriet is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).
/US Product Label Included/
/Therapeutic Research/ Left ventricular remodeling is a common complication of hypertension, and there is currently no effective treatment for its secondary myocardial fibrosis. Pirfenidone is a small-molecule antifibrotic drug with anti-inflammatory properties, commonly used to treat fibrotic diseases, but its effect on hypertension-induced myocardial fibrosis remains unclear. Therefore, we investigated whether pirfenidone could improve hypertension-induced left ventricular remodeling and whether hypertension-induced NLRP3 (Nod-like receptor pyridine domain protein 3, a key protein in NLRP3 inflammasome formation) is involved in its therapeutic mechanism. In this study, a mouse model of TAC-induced hypertension and left ventricular hypertrophy was established using pirfenidone. Survival rate, collagen deposition in histopathological examination, cardiac function assessed by echocardiography, concentrations of fibrosis-related inflammatory cytokines TGF-β1 and IL-1β in cardiac homogenates and in vitro cell cultures were measured by ELISA, reactive oxygen species (ROS) and inflammatory cell levels were detected by flow cytometry, and NLRP3 expression levels were detected by Western blotting and immunohistochemistry. The results showed that pirfenidone improved the survival rate of the TAC-induced hypertension and left ventricular remodeling mouse model and reduced myocardial fibrosis and the expression of inflammatory mediators. Pirfenidone attenuates IL-1β expression and its induced inflammatory and pro-fibrotic responses by inhibiting NLRP3 expression. Pirfenidone may be used to treat hypertension-induced myocardial fibrosis by inhibiting NLRP3-induced inflammation and fibrosis. Systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) has become a leading cause of SSc-related death. Despite various immunosuppressive therapies for SSc-ILD patients, no curative or effective treatment strategy has been developed. Therefore, the management of SSc-ILD patients remains a challenge. This article reports a case of a Chinese female SSc-ILD patient who was Scl-70 negative and responded well to pirfenidone treatment with no significant adverse reactions. The patient had presented with dry cough and exertional dyspnea for 2 months. Chest CT findings were consistent with the imaging features of fibrotic nonspecific interstitial pneumonia. Pulmonary function tests showed isolated diffusion impairment. After 11 weeks of pirfenidone treatment, the dry cough and dyspnea symptoms resolved. Both lung shadows and lung diffusion capacity improved. Pirfenidone may be an effective treatment option for early-stage systemic sclerosis-associated interstitial lung disease (SSc-ILD). A well-designed clinical trial is expected in the future.

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Drug Warning
Patients taking pirfenidone have experienced serum transaminase (ALT and/or AST) concentrations exceeding the upper limit of normal (ULN) by 3 times; bilirubin elevation is also rare. Clinical studies showed that 3.7% of patients taking pirfenidone had ALT or AST concentrations at least 3 times the ULN, compared to 0.8% of patients taking placebo; 0.3% of patients taking pirfenidone had ALT or AST concentrations exceeding 10 times the ULN. Elevated liver enzymes are reversible after dose adjustment or discontinuation of treatment. To date, there have been no reported cases of liver failure leading to liver transplantation or death due to pirfenidone use; however, the manufacturer notes that elevated transaminases and hyperbilirubinemia (without evidence of obstruction) are generally considered important predictors of severe liver injury, which may lead to death or the need for liver transplantation in some patients. Liver function tests, including ALT, AST, and bilirubin concentrations, should be performed before starting pirfenidone treatment and monthly for the first 6 months of treatment, followed by every 3 months thereafter. Patients with elevated liver enzymes may need to temporarily suspend treatment and/or reduce the dose. Smoking reduces peak plasma concentrations and systemic exposure to pirfenidone by 32% and 54%, respectively. The manufacturer recommends encouraging patients to quit smoking before starting pirfenidone and to avoid smoking during treatment. There are currently no adequate and well-controlled studies on the use of Esbriet in pregnant women. Pirfenidone has not shown teratogenicity in rats and rabbits. Because results from animal reproductive studies do not always predict human responses, Esbriet should only be used during pregnancy when the benefit to the patient outweighs the risks.
Adverse reactions occurring in ≥10% of patients taking pirfenidone and at a higher rate than in the placebo group include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, indigestion, dizziness, vomiting, anorexia, gastroesophageal reflux disease (GERD), sinusitis, insomnia, weight loss, and arthralgia.
For more complete data on pirfenidone (16 in total), please visit the HSDB record page.
Pharmacodynamics
Pirfenidone is a novel drug with anti-inflammatory, antioxidant, and anti-fibrotic properties. Pirfenidone (AMR69) may improve lung function and reduce the frequency of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF).

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Pirfenidone (AMR69) is a small molecule drug with antifibrotic and anti-inflammatory properties[1][2][3][4]
- Its mechanism of action includes inhibiting the expression of pro-fibrotic cytokines (TGF-β) and pro-inflammatory cytokines (TNF-α), thereby inhibiting the proliferation, migration, and epithelial-mesenchymal transition (EMT) of fibrosis-related cells[1][2][3][4]
- Pirfenidone (AMR69) has antifibrotic activity against lens epithelial cells and fibroblasts in vitro and antifibrotic activity against bleomycin-induced pulmonary fibrosis in mice in vivo[3][4]
- In animal models, it has no significant inhibitory effect on fibrosis associated with the proliferation, migration, or metastasis of triple-negative breast cancer cells[5] Pirfenidone (AMR69) has been widely used as a tool compound for studying fibrosis-related diseases, including pulmonary fibrosis and ocular fibrosis[3][4]

C12H11NO

185.22

185.084

53179-13-8

40632

White to light yellow solid powder

1.1±0.1 g/cm3

329.1±15.0 °C at 760 mmHg

96-97ºC

152.7±11.6 °C

0.0±0.7 mmHg at 25°C

1.592

1.82

0

1

1

14

285

0

ISWRGOKTTBVCFA-UHFFFAOYSA-N

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

5-methyl-1-phenylpyridin-2-one

S-7701, AMR-69; S 7701, AMR69; S7701, AMR-69; AMR 69; Pirfenidone; trade name: Pirespa; Pirfenex; Deskar, Esbriet; Etuary.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.75 mg/mL (14.85 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (14.85 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (11.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.08 mg/mL (11.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.08 mg/mL (11.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 6: 2% DMSO+30% PEG 300+ddH2O:10 mg/mL

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Solubility in Formulation 7: 9.09 mg/mL (49.08 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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Solubility in Formulation 8: 6.67 mg/mL (36.01 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 9: 20 mg/mL (107.98 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)