product name SW033291
Description: SW033291 is a potent and selective inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) with IC50 and Kiapp of 1.5 nM and 0.1 nM, respectively. 5-PGDH is a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. SW033291 also promotes tissue regeneration in mouse models of colon and liver injury.
References: Science. 2015 Jun 12;348(6240):aaa2340.
412.59
Formula
C21H20N2OS3
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)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19409973
| 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 Vivo | In 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 model | Mice receiving a bone marrow transplant, and Mouse models of colon and liver injury |
| Formulation & Dosage | Dissolved in 10% ethanol, 5% Cremaphor EL, 85% D5W; 10mg/kg; i.p. injection |
| References | Science. 2015 Jun 12;348(6240):aaa2340. |
