Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. N-Acetylcysteine (NAC)

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with idiopathic pulmonary fibrosis and mild-to-moderate lung function impairment, n=264 (acetylcysteine 133, placebo 131), mean age 67, 22% female, 60 weeks; lung only

   PANTHER-IPF measured change in forced vital capacity over 60 weeks and found none: -0.18 L on acetylcysteine versus -0.19 L on placebo (p=0.77), with no difference in mortality. The trial began with a third arm of prednisone, azathioprine and acetylcysteine, which the data and safety monitoring board stopped on 14 October 2011 at a planned interim analysis for increased death and hospitalisation versus placebo. No regulator has approved acetylcysteine for pulmonary fibrosis, and no liver, cardiac or skin fibrosis trial is on file.

   Source PubMed Central 1 primary source read for this row

2. Semaglutide

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with biopsy-defined MASH and stage F2-F3 liver fibrosis, n=800 (semaglutide 2.4 mg once weekly 534, placebo 266), 72-week interim analysis of the phase 3 ESSENCE trial; liver only

   Both endpoints were read from paired liver biopsies and they are separate results: steatohepatitis resolution with no worsening of fibrosis 62.9% vs 34.3% placebo, and fibrosis improvement with no worsening of steatohepatitis 36.8% vs 22.4% placebo. The FDA granted accelerated approval in August 2025 for non-cirrhotic MASH with moderate to advanced fibrosis (F2-F3); cirrhosis was not studied, and no trial of any other organ's fibrosis is on file.

   Source PubMed Central 2 primary sources read for this row

3. Carnosic Acid

   animal in vivo Direct outcome Not approved for this condition

   Who was studied

   male Sprague-Dawley rats, bile-duct-ligation liver fibrosis model, n=8 per group across 5 groups; carnosic acid 30 or 60 mg/kg/day intragastrically for 21 days; liver only

   Liver collagen deposition was measured directly in tissue by Masson staining, with alpha-smooth-muscle actin and collagen 1 protein also reduced. The compound tested is carnosic acid, a rosemary diterpene and not a peptide despite the record's name. No human study in any organ is on file.

   Source PubMed Central 1 primary source read for this row

4. GHK-Cu

   animal in vivo Direct outcome Not approved for this condition

   Who was studied

   C57BL/6J mice, bleomycin-induced pulmonary fibrosis (bleomycin 3 mg/kg by tracheal instillation); GHK-Cu 0.2, 2 or 20 mcg/g/day intraperitoneally on alternate days; lung only

   Lung histology and collagen deposition were measured in tissue and were reduced by the copper complex GHK-Cu. A separate mouse study in the same model used uncomplexed GHK, a different molecule, so the two should not be pooled. No human pulmonary fibrosis study of GHK-Cu is on file, and the topical human work on this compound measured skin appearance, not fibrosis.

   Source PubMed 2 primary sources read for this row

5. Thymosin Beta-4

   animal in vivo Direct outcome Not approved for this condition

   Who was studied

   female C57BL/6 mice, chronic ethanol feeding plus binge ethanol and LPS liver injury model; full-length 43-residue thymosin beta-4, 1 mg/kg intraperitoneally daily for 1 week; liver only

   Liver collagen was measured directly in tissue by Sirius Red staining and hydroxyproline content, both of which fell with treatment. The molecule given was full-length thymosin beta-4, not the 7-residue LKKTETQ fragment sold as TB-500, so this evidence does not transfer to that fragment. No human fibrosis trial of thymosin beta-4 in any organ is on file.

   Source PubMed Central 1 primary source read for this row

6. Angiotensin (1-7)

   animal in vivo Surrogate marker Not approved for this condition

   Who was studied

   male Sprague-Dawley rats, unilateral acid-aspiration lung injury, n=8 treated and n=7 vehicle; angiotensin-(1-7) 300 mcg/kg/day by subcutaneous osmotic mini-pump for 2 weeks; lung only

   Fibrosis was inferred from lung hydroxyproline content, a biochemical collagen assay, which was 649 mcg/lung with angiotensin-(1-7) versus 1117 mcg/lung with vehicle (p=0.006); no histological fibrosis stage and no lung function endpoint was reported. Human trials of angiotensin-(1-7) exist in metastatic sarcoma and in COVID-19, neither of which measured fibrosis, and no human fibrosis trial in any organ is on file.

   Source PubMed Central 1 primary source read for this row

Checked, and nothing recorded

1 compound was checked against fibrosis and produced no gradeable row.

• Relaxin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.