SW03329115-PGDH enzyme inhibitor CAS# 459147-39-8 |
- StemRegenin 1 (SR1)
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Quality Control & MSDS
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| Cas No. | 459147-39-8 | SDF | Download SDF |
| PubChem ID | 3337839 | Appearance | Powder |
| Formula | C21H20N2OS3 | M.Wt | 412.59 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 50 mg/mL (121.19 mM; Need ultrasonic) | ||
| Chemical Name | 2-butylsulfinyl-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine | ||
| SMILES | CCCCS(=O)C1=C(C2=C(S1)N=C(C=C2C3=CC=CC=C3)C4=CC=CS4)N | ||
| Standard InChIKey | LCYAYKSMOVLVRL-UHFFFAOYSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | High affinity 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor (Ki = 0.1 nM). Increases PGE2 levels in A549 cells in vitro, as well as in bone marrow, colon, lung and liver in mice. Promotes hematopoiesis, recovery from DSS-induced colitis, and hepatocyte proliferation after partial hepatectomy in mice. |
SW033291 Dilution Calculator
SW033291 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4237 mL | 12.1186 mL | 24.2371 mL | 48.4743 mL | 60.5928 mL |
| 5 mM | 0.4847 mL | 2.4237 mL | 4.8474 mL | 9.6949 mL | 12.1186 mL |
| 10 mM | 0.2424 mL | 1.2119 mL | 2.4237 mL | 4.8474 mL | 6.0593 mL |
| 50 mM | 0.0485 mL | 0.2424 mL | 0.4847 mL | 0.9695 mL | 1.2119 mL |
| 100 mM | 0.0242 mL | 0.1212 mL | 0.2424 mL | 0.4847 mL | 0.6059 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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SW033291 is a potent inhibitor of 15-PGDH enzyme with IC50 value of 1.5 nM and dissociation constant Ki app value of 0.1 nM. SW033291 inhibits 15-PGDH with noncompetitive pattern. SW033291 shifted the 15-PGDH melting temperature by 13.5°C. [1]
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. [1]
The phenotype of mice injected with SW033291 closely matched with 15-PGDH knockout mice (10mg/kg). SW033291 induced a two-fold increase in PGE2 levels in bone marrow, colon, lung, and liver. Importantly, no toxicity was induced by injecting SW033291 for inhibition of 15-PGDH in adult mice. Mice injected with SW033291 exhibited many good benefits, such as doubling peripheral neutrophils, a 65% increase in marrow SKL cells, a 71% increase in marrow SLAM cells, and 55% increases in the numbers of hematopoietic colonies. [1]
Reference:
1. Zhang Y, Desai A, Yang SY et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240). pii: aaa2340.
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Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy.[Pubmed:28887458]
Sci Rep. 2017 Sep 8;7(1):11009.
The mechanisms underpinning the failure of inflammation to resolve in diseased musculoskeletal soft tissues are unknown. Herein, we studied bioactive lipid mediator (LM) profiles of tendon-derived stromal cells isolated from healthy donors and patients with chronic tendinopathy. Interleukin(IL)-1beta treatment markedly induced prostaglandin biosynthesis in diseased compared to healthy tendon cells, and up regulated the formation of several pro-resolving mediators including 15-epi-LXA4 and MaR1. Incubation of IL-1beta stimulated healthy tendon cells with 15-epi-LXA4 or MaR1 down-regulated PGE2 and PGD2 production. When these mediators were incubated with diseased cells, we only found a modest down regulation in prostanoid concentrations, whereas it led to significant decreases in IL-6 and Podoplanin expression. In diseased tendon cells, we also found increased 15-Prostaglandin Dehydrogenase (15-PGDH) expression as well as increased concentrations of both 15-epi-LXA4 and MaR1 further metabolites, 15-oxo-LXA4 and 14-oxo-MaR1. Inhibition of 15-PGDH using either indomethacin or SW033291 significantly reduced the further conversion of 15-epi-LXA4 and MaR1 and regulated expression of IL-6, PDPN and STAT-1. Taken together these results suggest that chronic inflammation in musculoskeletal soft tissues may result from dysregulated LM-SPM production, and that inhibition of 15-PGDH activity together with promoting resolution using SPM represents a novel therapeutic strategy to resolve chronic tendon inflammation.
Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair.[Pubmed:28398755]
J Med Chem. 2017 May 11;60(9):3979-4001.
The enzyme 15-prostaglandin dehydrogenase (15-PGDH) catalyzes the first step in the degradation of prostaglandins including PGE2. It is a negative regulator of tissue repair and regeneration in multiple organs. Accordingly, inhibitors of 15-PGDH are anticipated to elevate in vivo levels of PGE2 and to promote healing and tissue regeneration. The small molecule SW033291 (1) inhibits 15-PGDH with Ki = 0.1 nM in vitro, doubles PGE2 levels in vivo, and shows efficacy in mouse models of recovery from bone marrow transplantation, ulcerative colitis, and partial hepatectomy. Here we describe optimized variants of 1 with improved solubility, druglike properties, and in vivo activity.
TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.[Pubmed:26068857]
Science. 2015 Jun 12;348(6240):aaa2340.
Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.
