In vitro activity: BT-11 is a first-in-class, potent, orally available and selective modulator of LANCL2 (Lanthionine synthetase C-like 2) which is a novel therapeutic target for inflammatory and autoimmune diseases and diabetes, exerts anti-inflammatory and insulin-sensitizing effects. BT-11 at high doses has an excellent safety profile up to 1000 mg/kg/day. It has demonstrated therapeutic efficacy in 3 validated mouse models of colitis at doses as low as 8 mg/kg/d; It protects from IBD by targeting LANCL2. BT-11 has potential to be a safe and effective orally active therapeutic for IBD. The oral treatment with BT-11 (8 mg/kg/d) in a mouse model of IBD resulted in lowering the disease activity index, decreasing colonic inflammatory lesions by 4-fold, and suppressing inflammatory markers (e.g., TNF-α, and interferon-γ) in the gut. Furthermore, studies in LANCL2-/- mice demonstrated that loss of LANCL2 abrogated beneficial actions of BT-11, suggesting high selectivity for the target. In conclusion, BT-11 merits continued development as a LANCL2-based, first-in-class orally active therapeutic for IBD.

Kinase Assay: LANCL2 engagement produces an increase of PKA, followed by an accumulation of cAMP in the cytoplasm. BT-11 treatment splenocytes shows a dose–response increase of cAMP production. BT-11 stimulates cAMP production by activating the LANCL2 pathway.