EL244

EL244 is a dua Autotaxin ( ATX ) ( IC₅₀ = 50 nM) inhibitor and PPARγ ( IC₅₀ = 1.3 μM; K d = 1.3 μM) agonist. EL244 demonstrates low cytotoxicity in human HepG2 cells ( EC 50 = 81.2 μM) with minimal inhibition of the cardiac hERG potassium channel (12% at 25 μM). EL244 significantly reduces pulmonary Lysophosphatidic Acid (LPA) levels, attenuates fibrosis, and restores respiratory function with limited systemic absorption in vivo. EL244 can be used for idiopathic pulmonary fibrosis and interstitial lung disease (ILD) research ^[1].

In Vivo, EL244 (15 mg/kg, 15 mg/kg, once) exhibits favorable lung-targeted pharmacokinetics, characterized by high pulmonary retention, slow local clearance, and limited systemic absorption in the BLM (Bleomycin) (oropharyngeal aspiration, 0.8 U/Kg)-induced mice model of pulmonary fibrosis^[1]. EL244 (15 mg/kg, inhaled administration, once daily for 15 days) post and before BLM administration has anti-fibrotic prophylactic effects in the BLM (oropharyngeal aspiration, 0.8 U/Kg)-induced model of pulmonary fibrosis in the BLM (oropharyngeal aspiration, 0.8 U/Kg)-induced mice model of pulmonary fibrosis^[1]. EL244 (30 mg/kg, i.p., once) demonstrates favorable pharmacokinetics, achieving a plasma concentration of 40 μM within 1 hour, maintaining levels around 35 μM for up to 3 hours, and remaining detectable at approximately 15 μM even 9 hours post-dose, with its maximal pharmacodynamic effect coinciding at the 3-hour time point in the BLM (oropharyngeal aspiration, 0.8 U/Kg)-induced mice model of pulmonary fibrosis^[1].

References:
[1]. Alexios N, et al. An aerosolised dual-action Autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis. Biorixiv. November 13, 2025.