myofibroblasts

1. 3-Butylidenephthalide (Butylidene phthalide) has antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level, inhibited the activity of yeast-α-glucosidase (IC(5) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM.

PDE1-IN-8 (Compound 3f) acts as an inhibitor of PDE1, with an IC50 of 11 nM. It hinders cAMP and cGMP signaling pathways, impeding the differentiation and proliferation of cells into myofibroblasts, and demonstrates antifibrotic effects in the Bleomycin-induced rat model of pulmonary fibrosis.

(E)-SIS3 (SIS3) is a Smad3 inhibitor (IC50=3 μM) and is selective. (E)-SIS3 inhibits the differentiation of fibroblasts into myofibroblasts via TGF-β1.

(Rac)-Indoximod (1-Methyl-DL-tryptophan) is a potent inhibitor of indoleamine 2,3-dioxygenase (IDO). Combined treatment with IFN-γ and (Rac)-Indoximod significantly suppresses the activity of α-SMA-expressing human cardiac myofibroblasts (hCMs) and promotes apoptosis by up-regulating the genes IRF-1, Fas, and FasL, effectively improving cardiac fibrosis[1].

Tat-Gap 19, a peptide inhibitor of connexin43 (Cx43) hemichannels, is derived from the HIV-1 Tat protein transduction domain fused with a nine-amino acid sequence from Cx43 residues 128-136. This compound, at a concentration of 10 µM, effectively suppresses glutamate-induced ATP release in primary rat hepatocytes, indicating inhibition of Cx43 hemichannel activity. Furthermore, Tat-Gap 19 demonstrates therapeutic potential by significantly reducing infarct volume in a mouse cerebral ischemia-reperfusion injury model following middle cerebral artery occlusion (MCAO) at a dosage of 25 mg/kg. Moreover, its intraperitoneal administration at 1 mg/kg per day ameliorates fibrosis and decreases the area of hepatic stellate cells, the precursors to myofibroblasts, expressing α-smooth muscle actin (α-SMA), in a model of thioacetamide-induced liver damage. Additionally, it enhances superoxide dismutase (SOD) activity in hepatic cells from the treated mice, indicating its antioxidative benefits.

TOP1288 is a narrow-spectrum kinase inhibitor targeting P38α, Src, and Syk kinases, with IC 50 values of 116nM, 24nM, and 659nM, respectively. It effectively inhibits inflammatory cytokine release from inflamed biopsies and myofibroblasts [1].

STX-100 is a humanized antibody targeting integrin αvβ6 (ITGAV & ITGB6) with anti-tumor activity, inhibits pSMAD2, inhibits the conversion of fibroblasts to myofibroblasts, and can be used to study idiopathic pulmonary fibrosis (IPF).