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    SW-033291
    SW-033291

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0857
    CAS #: 459147-39-8Purity ≥98%

    Description: SW033291 (SW-033291; SW 033291) is a selective and high affinity inhibitor of the prostaglandin-degrading enzyme 15-PGD (15-hydroxyprostaglandin dehydrogenase) with potential kidney and liver protective effects. It inhibits 15-PGDH with an IC50 and Kiapp of 1.5 nM and 0.1 nM, respectively. Inhibition of 15-PGDH by SW033291 could alleviate lipopolysaccharide (LPS)-induced acute kidney injury (AKI) by regulating the apoptosis, autophagy, and oxidative stress rather than inflammation in mice. 

    References: Science. 2015 Jun 12;348(6240):aaa2340.

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    Molecular Weight (MW)412.59
    FormulaC21H20N2OS3
    CAS No.459147-39-8
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 83 mg/mL (201.2 mM)
    Water: <1 mg/mL
    Ethanol: 32 mg/mL warmed (77.6 mM) 
    Other infoChemical Name: 2-(Butylsulfinyl)-4-phenyl-6-(2-thienyl)-thieno[2,3-b]pyridin-3-amine
    InChi Key: LCYAYKSMOVLVRL-UHFFFAOYSA-N
    InChi Code: InChI=1S/C21H20N2OS3/c1-2-3-12-27(24)21-19(22)18-15(14-8-5-4-6-9-14)13-16(23-20(18)26-21)17-10-7-11-25-17/h4-11,13H,2-3,12,22H2,1H3
    SMILES Code: NC1=C(S(CCCC)=O)SC2=NC(C3=CC=CS3)=CC(C4=CC=CC=C4)=C21
    SynonymsSW-033291; SW033291; SW 033291


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    In Vitro

    In vitro activity: In Vaco-503 cells, SW033291 (2.5 μM) decreases cellular 15-PGDH enzyme activity by 85%. Treatment of A549 cells with SW033291 increased PGE2 levels by 3.5-fold at 500 nM, with EC50 value of ~75 nM. In CD45 cells, SW033291 treatment induced a greater than four-fold increase in expression of CXCL12 and SCF. In SKL cells, SW033291 had no significant effects on expression of CXCL12, SCF, CXCR4, survivin, or JAG1. SW033291 also increased cyclic AMP levels in CD45 cells. SW033291 treatment increases the expression of cytokines from the hematopoietic niche


    Kinase Assay:  For initial characterization of inhibition of 15-PGDH enzyme activity by SW033291, reactions were assembled with experiment specific concentrations of 15-PGDH enzyme, and experiment specific concentrations of SW033291, plus 150 μM NAD(+) and 25 μM PGE2 in reaction buffer (50 mM Tris-HCl, pH7.5, 0.01% Tween 20). The reaction mix was incubated for 15 mins at 25°C in an Envision Reader. Enzyme activity was determined by following generation of NADH as assayed by recording fluorescence at Ex/Em = 340 nM/485 nM every 30s for 3 mins, commencing immediately after addition of PGE2. IC50 values were calculated with GraphPad Prism 5 software using the sigmoidal dose-response function and plotted against SW033291 concentration.


    Cell Assay: In CD45- bone marrow cells, SW033291 inhibited 15-PGDH, increased tissue levels of PGE2, and induced CXCL12 and SCF expression, which in turn accelerated homing of transplanted hematopoietic stem cells, generation of mature blood elements, as well as posttransplant recovery of normal blood counts. In addition, inhibiting 15-PGDH also stimulated cell proliferation after injury to colon or liver, and accelerated repair of these tissues.

    In VivoIn mice receiving a bone marrow transplant, SW033291 (10 mg/kg, i.p.) promotes hematopoietic recovery. In mouse models of colon and liver injury, SW033291 (10 mg/kg, i.p.) reduces the levels of colitis-associated inflammatory cytokines, protects mice from colitis, and promotes liver regeneration.
    Animal modelMice receiving a bone marrow transplant, and Mouse models of colon and liver injury
    Formulation & DosageDissolved in 10% ethanol, 5% Cremaphor EL, 85% D5W; 10mg/kg; i.p. injection
    References

    Science. 2015 Jun 12;348(6240):aaa2340.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    SW033291

    Effect of 15-PGDH inhibition on bone marrow. Science. 2015 Jun 12;348(6240):aaa2340.

    SW033291

    15-PGDH inhibition protects mice from DSS-induced colitis. Science. 2015 Jun 12;348(6240):aaa2340.

     


    SW033291

    Liver regeneration in mice after partial hepatectomy. Science. 2015 Jun 12;348(6240):aaa2340.

    SW033291

    Biological effects of 15-PGDH inhibition in mice. Science. 2015 Jun 12;348(6240):aaa2340.

    SW033291

    SW033291 potentiates hematopoietic recovery after bone marrow transplantation. Science. 2015 Jun 12;348(6240):aaa2340.



    SW033291


    15-PGDH inhibition increases BrdU incorporation in colonic crypts. Science. 2015 Jun 12;348(6240):aaa2340.


     


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