Snail IN-1

Snail IN-1 is an orally active Snail inhibitor with a Ka of 0.36 μM.Snail IN-1 disrupts Snail - CBP interaction, accelerates Snail protein degradation, reduces Snail acetylation, increases Snail polyubiquitination, and selectively downregulates Snail protein without altering other EMT transcription factors.Snail IN-1 reduces atherosclerotic plaque burden, modulates inflammation and plaque stability factors, downregulates CCL5, CXCL10, MMP2, and MMP9, and upregulates α-smooth muscle actin.Snail IN-1 exerts anti-inflammatory and plaque-stabilizing properties.Snail IN-1 can be used for the research of atherosclerosis ^[1].

In Vivo, Snail IN-1 (25-50 mg/kg; i.g.; daily; 4 weeks) exerts dose-dependent antiatherosclerotic effects in high-fat diet-fed ApoE-/- mice, reducing plaque burden by decreasing inflammatory chemokines (CCL5, CXCL10) and matrix-degrading enzymes (MMP2, MMP9), while increasing plaque-stabilizing factors (collagen, α-SMA)^[1]. Snail IN-1 (2000 mg/kg; i.g.; single dose) is well-tolerated in C57BL/6 mice, causing no acute organ damage or functional disturbances^[1].

In Vitro, Snail IN-1 (compound S29) (0.1-10 μM; 48 h) potently downregulates the protein level of Snail in HUVECs in a concentration-dependent manner in vitro without altering the mRNA level of Snail, suggesting that its regulatory effect occurs at the post-transcriptional stage^[1]. Snail IN-1 (5-60 μM; 48 h) shows no significant cytotoxicity against HUVECs even at concentrations up to 60 μM after 48 h of incubation^[1]. Snail IN-1 (5 μM; 0-240 min) accelerates the degradation of Snail protein and reduces its stability in HUVECs^[1]. Snail IN-1 (2.5-20 μM; 48 h) specifically downregulates the protein level of Snail in HUVECs, without affecting the protein or mRNA levels of other EMT transcription factors (Zeb1, Slug, Twist)^[1]. Snail IN-1 (5 μM; 24 h) promotes Snail degradation by disrupting the interaction between Snail and CBP, reducing the acetylation level of Snail, and increasing the polyubiquitination of Snail in human umbilical vein endothelial cells (HUVECs)^[1]. Snail IN-1 (2.5 μM; 24 h) significantly downregulates the mRNA levels of pro-atherosclerotic factors (CCL5, CXCL10, MMP-9, MMP-2) in TNF-α-stimulated HUVECs^[1]. Snail IN-1 (1.25-5 μM; 24 h) inhibits the expression of CCL5 and CXCL10 proteins in TNF-α-stimulated HUVEC in a concentration-dependent manner^[1]. Snail IN-1 (2.5 μM; 24 h) impairs monocyte recruitment by altering the secretory profile of TNF-α-stimulated HUVEC^[1].

References:
[1]. Zeng Z, et al. Discovery of Novel Snail Inhibitors Derived from Omeprazole for Antiatherosclerotic Therapy: A Structure-Based Approach. J Med Chem. 2026;69(4):5002-5023.