Table 1 In vitro/in vivo studies and clinical trials on medications affected fibrotic disorder-affected fibrosis genes
Product name | Description and fibrosis-affected mechanism | Status of clinical development for fibrotic disorders (in vivo/in vitro studies) | NCT number for fibrosis disorders | Proposed dose for fibrotic disorders | Side effects |
|---|---|---|---|---|---|
Imatinib (Gleevec, Glivec STI-571, CGP 57148) | Specific tyrosine kinase receptor inhibitor, e.g., Imatinib mesylate binds to the amino acids of the BCR/ABL tyrosine kinase ATP binding site | Phase II, III clinical trial nephrogenic systemic fibrosis Phase II and III clinical trial IPF and pulmonary fibrosis Phase II clinical trial SSc | NCT00677092 NCT00981942 NCT00131274 NCT00613171 | 600 mg orally, once per day for approximately 2 years | Include vomiting, diarrhea, muscle pain, headache, rash, fluid retention, gastrointestinal bleeding, bone marrow suppression, liver problems, and heart failure |
Ambrisentan (Letairis) | A endothelin receptor antagonist and is selective for the type ETA receptor | Phase II, III clinical trial idiopathic pulmonary fibrosis Clinical study SSc-PAH | NCT00768300 NCT00879229 NCT03074149 NCT03827200 | 5 or10 mg tablet administered orally once daily for 4 weeks | Stuffy nose, runny nose, sinus pain, headache, abdominal/stomach pain, vomiting, constipation, and sore throat |
Sirolimus (Rapamycin) | A macrolide compound that is used to mTOR inhibition | Phase II, III clinical trial idiopathic pulmonary fibrosis Phase I clinical trial SSc | NCT03502902 NCT00241189 | 6 mg daily for one year | Bleeding from the gums or nose, bone pain confusion, blurred vision severe vomiting |
MMI-0100 | A novel cell-permeant peptide inhibitor of MAPKAP kinase II (MK2) | Clinical study and trial acute inflammatory response in fibrosis | aNCT02515396 (Unacceptable safety) | Not available | Hepatotoxicity, cardiotoxicity, and undisclosed CNS toxicity |
Salirasib (Trans-farnesylthiosalicylic acid [FTS]) | A salicylic acid that preventing activation of Ras signaling | Hepatic fibrosis/HSC | Not available | Not available | Habituation, excitation, insomnia, depression, premature closure of epiphyses |
Bosentan (Tracleer) | A dual endothelin receptor antagonist medication | Phase I, II, III, IV clinical trial in systemic sclerosis and digital ulcers | NCT00226889 NCT01241383 NCT01395732 NCT02798055 aNCT01836263 | 62.5 mg twice daily (b.i.d) for 4 weeks and then 125 mg b.i.d for 20 weeks | Flushing, upset stomach, fatigue, tiredness, headache, swelling of the feet/ankles/legs, and itching |
PP2 | A selective inhibitor for Src-family kinases (PI3K/Akt signaling) | Not available | Not available | Not available | Tiredness, changes in vaginal bleeding, breast tenderness |
U0126 | A highly selective inhibitor of both MEK1/2, a type of MAPK/ERK kinase | Clinical study in pulmonary fibrosis | Not available | Not available | Not available |
MK2206 | A inhibitor of pan-Akt | Not available | Not available | Not available | Not available |
Tocilizumab (Actemra, Atlizumab) | A humanized monoclonal antibody against the interleukin-6 receptor (IL-6R) | Phase III clinical trial in systemic sclerosis | NCT02453256 NCT01532869 aNCT03610217 | 162 mg subcutaneous once weekly for 48 weeks | Neutropenia, rash thrombocytopenia, hepatic injury, anaphylaxis, and urticarial |