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Multiple Actions of Sphingosine-1-Phosphate (S1P)

MjultipleActionsOfS1P

Uhlig, Am J Respir Crit Care Med, 178:1100, 2008

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S1P2 Receptor Signaling

S1P2ReceptorSignaling

S1P1  Signaling Stabilizes Barrier Integrity and Promotes Cell Survival
Garcia, J Clin Invest, 108:689, 2001; Paik, Genes Dev, 18:2392, 2004 ;
Uhlig, Am J Respir Crit Care Med, 178:1100, 2008
 

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AB22 – A New Drug to Treat Fibrotic Diseases

  • Arroyo Biosciences, LLC has discovered proprietary, potent, & selective S1PR2 antagonists.
  • Compounds have low toxicity and good pharmacokinetics.
  • Compounds show high specificity for S1PR2, minimal binding to other receptors (Cerep screen).
  • AB22 shows excellent ADME properties and improved pharmacokinetics by oral dosing.
  • AB22 has excellent safety profile
    • Negative in Ames and micronucleus assay, no toxicity in MTT assay.
    • No significant CYP inhibition against 5 isoforms screened.
    • No toxicity at 100mg/kg/day for 7 days in normal female mice.
  • AB22 has preventive and therapeutic effects in a bleomycin lung fibrosis model.
  • AB22 reduces fibrotic gene expression in TGF-β treated human fibroblasts and human Scleroderma lung fibroblasts.
     
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