Table 3 Emerging Anti-Pulmonary fibrosis drugs in clinical development

synthetic compounds

Pirfenidone

Antifibrotic; anti-inflammatory; modulates growth factors (TGF-β, PDGF); inhibits fibroblast proliferation and collagen synthesis, and antioxidant

Phase III

[170]

Nintedanib

Tyrosine kinase inhibitor targeting PDGF, FGF, and VEGF receptors; inhibits fibroblast proliferation, migration, and differentiation.

Phase III

[171]

Omipalisib

PI3K/mammalian target of rapamycin (mTOR) inhibitor; inhibit PI3K signaling; inhibit Akt phosphorylation.

Phase I

[172]

GSK3008348

Small molecule αvβ6 integrin inhibitor; selective and high affinity binding to the αvβ6 integrin; inhibit TGFβ activation

Phase I

[173]

GLPG1690

First-in-class ATX inhibitor; suppression of LPA-driven fibrosis; attenuate collagen deposition

Phase II

[174]

PBI-4050

Inhibit the differentiation of fibroblasts to myofibroblasts; antagonist ligand affinity towards the G-protein coupled receptors GPR40 and GPR84.

Phase II

[175]

TD139

Small-molecule Galectin-3 inhibitor; selectively binds to the carbohydrate recognition domain (CRD) of Galectin-3.

Phase II

[176]

natural compounds

Curcumin

Inhibit the TGF-β, NF-κB, mitogen-activated protein kinase, TLRs, and PPARγ/PDGFβ signaling pathway; inhibit fibroblast proliferation.

preclinical

[177]

Resveratrol

Anti-oxidation, antibacterial, anti-inflammatory, growth inhibitory, anti-platelet aggregation, pro-apoptotic.

preclinical

[178]

Baicalin

Inhibit the NLRP3 inflammasome and TLR4/JNK/ERK/NF-κB pathway; anti-inflammatory, antimicrobia.

preclinical

[179]

Quercetin

Inhibition of TGF-β/Smad Signaling; anti-Inflammatory; regulation of autophagy & senescence.

Phase I

[180]

Salvianolic acid B

Relieve peroxide-stress injury; regulate TNF-α and other inflammatory cytokines and fibrosis-related cytokines.

preclinical

[181]

Celastrol

Suppression of TGF-β/Smad signaling; inhibition of NF-κB and NLRP3 Inflammasome, antioxidant.

preclinical

[182]

Antibodies

Tocilizumab

Blockade of IL-6 signaling; anti-inflammatory effects; inhibition of fibroblast activation.

Phase III

[183]

Pamrevlumab

Inhibition of CTGF Activity; reduction of ECM accumulation; anti-inflammatory.

Phase II

[184]

Simtuzumab

Inhibition of LOXL2-mediated ECM crosslinking; suppression of fibroblast activation and TGF-β signaling

Phase II

[185]

Tralokinumab

Blockade of IL-13 signaling; suppression of fibroblast activation and differentiation

Phase II

[186]