α-sma

Sinefungin (Adenosyl-Ornithine) is an effective inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. Sinefungin is a SET7 9 inhibitor and ameliorates renal fibrosis by inhibiting H3K4 methylation.

AA147 (ATF6-activator-147) is a small molecule endoplasmic reticulum (ER) proteostasis regulator. The selectively activates ATF6 arm of the unfolded protein response (UPR) .It acts as a prodrug that preferentially triggers ATF6 signaling through a mechanism involving localized metabolic activation and selective covalent modification of ER resident proteins that regulate ATF6 activity.

Branaplam (LMI 070) is a highly potent, selective and orally active small molecule SMN2 splicing modulator.

Numidargistat dihydrochloride (CB-1158 dihydrochloride) is an orally active and highly effective arginase (ARG1) inhibitor, an immuno-oncology agent that inhibits TGF-β2-induced subcapsular cataract by reducing the proliferation of lens epithelial cells (LEC) and decreasing the expression of fibronectin, α-SMA, collagen 1A1, and vimentin.

SRI-011381 hydrochloride, a new-type agonist of the TGF-beta signaling pathway, is utilized in the treatment of Alzheimer's disease.

TP-DEA2, a prodrug of triptolide, effectively inhibits bleomycin-induced pulmonary fibrosis and inflammatory responses. It significantly reduces the production of α-SMA.

ALK5-IN-82 is a potent and selective inhibitor of activin receptor-like kinase 5 (ALK5), demonstrating an IC50 value of 9.1 nM. This compound effectively suppresses the expression of α-smooth muscle actin (α-SMA), collagen I, and the proteinases tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinase 13 (MMP-13) in human umbilical vein endothelial cells induced by transforming growth factor-β. ALK5-IN-82 shows potential for use in research related to cardiac fibrosis.

JNK-1-IN-4 (Compound E1) is an inhibitor of JNK, targeting JNK-1, JNK-2, and JNK-3 with IC50 values of 2.7, 19.0, and 9.0 nM, respectively. This compound inhibits the phosphorylation of c-Jun and reduces the expression of TGF-β1-induced EMT markers (such as fibronectin and α-SMA). JNK-1-IN-4 exhibits favorable pharmacokinetic properties with a bioavailability of 69%. Additionally, it demonstrates antifibrotic effects in a Bleomycin-induced mouse model of idiopathic pulmonary fibrosis.

GED-0507-34 Levo ((S)-3-(4-Aminophenyl)-2-methoxypropanoic acid), an orally available PPARγ modulator for amelioration of inflammation-driven intestinal fibrosis, decreased the expression of the pro-fibrotic genes Acta2, COL1a1, and Fn1, reduced the protein levels of α-SMA and collagen I-II, the main markers of fibrosis, as well as the major components of the TGFβ Smad pathway, and decreased the expression of IL-13, CTGF, TGFB and ACTA1, and inhibited TGF-β-induced activation of fibroblasts and IECs cell lines.

Anti-NASH agent 2 (compound 21) is an inhibitor of neolipogenesis activity and α-SMA gene expression. It improves hepatic steatosis, edema, inflammatory infiltration, and liver fibrosis in NASH mouse models.

SIRT2-IN-17 (compound Z18) is a potent inhibitor of SIRT2, effectively reducing the expression of α-SMA and p-Smad2 3.

TRPV1-IN-3 (compound 14) is a TRPV1 inhibitor utilized in idiopathic pulmonary fibrosis research. It demonstrates antifibrotic activity in vitro (IC50 = 0.51 μM) by inhibiting the TGF-β Smads and MAPK pathways, thereby affecting the expression of fibrosis markers collagen I and α-SMA. In vivo, TRPV1-IN-3 significantly reduces collagen deposition in lung tissue, improves alveolar structure, and increases survival rates in mice with Bleomycin-induced pulmonary fibrosis.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

5-HT2B antagonist-2 (Compound 19c) is a 5HT2B receptor antagonist with an IC50 of 1.09 nM. It effectively downregulates the expression of fibrosis-related genes α-SMA, Timp1, Col1a1, and Col3a1, significantly reducing cellulose deposition. In a CCl4-induced liver fibrosis mouse model, it decreases the fibrotic area and inhibits the progression of fibrosis. This compound is useful for research into immune-inflammatory related diseases, particularly pulmonary fibrosis.

Autotaxin-IN-7 (45) is a pyridine-2-carboxylic acid derivative exhibiting sub-nanomolar inhibition of ATX (IC50 = 0.086 nM) and features excellent cardiac safety (hERG > 30 μM) with minimal toxicity to fibroblasts. It inhibits the TGF-β/Smad signaling pathway, reducing α-smooth muscle actin (α-SMA) and extracellular matrix components (ECM). Autotaxin-IN-7 (45) can be used in pulmonary fibrosis research.

C18 dihydro Ceramide is a bioactive sphingolipid and precursor in the de novo synthesis of C18 ceramide that lacks the 4,5-trans double bond. [1] Increased C18 dihydroceramide lipid levels lead to increased triacylglycerol storage and autophagosome accumulation as well as upregulation of the fibrosis markers α-SMA and FGF2 in Chang and LX-2 liver cells. C18 dihydro Ceramide is elevated in the plasma of pre-diabetics up to 9 years prior to the onset of type 2 diabetes. [2] It is also elevated in the skin of patients with lesional atopic dermatitis.[3]

SRI-011381, a new-type agonist of the TGF-beta signaling pathway, is utilized in the treatment of Alzheimer's disease.

Loureirin A has an inhibitory effect on platelet activation, perhaps through an impairment of PI3K/Akt signaling.Loureirin A negatively affects agonist-induced platelet aggregation such as collagen, collagen-related peptide (CRP), ADP and thrombin. Lourei

(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].

TGFβ1-IN-1 is an orally active TGF-β1 inhibitor that inhibits the production of TGF-β1-induced fibrotic markers (α-SMA and fibronectin) and can be used for the study of cancer and autoimmune diseases.

TGFβ-IN-2 (Compound 9d) effectively inhibits TGF-β-induced accumulation of total collagen in NRK-49F cells, with an IC50 value of 4.31 μM. It also suppresses the TGF-β-induced in vitro expression of COL1A1, α-SMA, and p-Smad3. Additionally, TGFβ-IN-2 shows promise as a potential anti-fibrosis compound for in vivo applications through oral administration [1].

NTU281 is a potent inhibitor of transglutaminase-2 that reduces the elevation of serum creatinine and proteinuria in diabetic rats and decreases glomerular type I collagen accumulation, Hic-5 and α-SMA expression, as well as apoptosis, and can be used in studies of diabetes-induced glomerulosclerosis.

ATX inhibitor 11 is a potent inhibitor of ATX (autotaxin) (IC50: 2.7 nM). ATX inhibitor 11 alleviates the severity of fibrotic tissue and effectively reduces the deposition of α-SMA, a biomarker of fibrosis, in a mouse model of fibrosis. ATX inhibitor 11 can be used to study lung fibrosis.

FXR agonist 3 is an anti-NASH compound with antifibrotic and anti-fibrotic activity, inhibiting the expression of COL1A1, TGF-β1, α-SMA, and TIMP1, with an IC50 value of 8.19 μmol/L for COL1A1. FXR agonist 3 ameliorates CDAHFD and BDL-induced liver injury in vivo by activating FXR.