WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522396
CAS#: 459147-39-8
Description: SW033291 is a potent and selective 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme inhibitor. 15-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. 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.
Hodoodo Cat#: H522396
Name: SW033291
CAS#: 459147-39-8
Chemical Formula: C21H20N2OS3
Exact Mass: 412.07
Molecular Weight: 412.580
Elemental Analysis: C, 61.13; H, 4.89; N, 6.79; O, 3.88; S, 23.31
Synonym: SW033291; SW 033291; SW 033291.
IUPAC/Chemical 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
Appearance: Yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | SW033291 is a potent and high-affinity inhibitor of 15-PGDH with a Ki of 0.1 nM. SW033291 increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 also promotes tissue regeneration. |
| In vitro activity: | To investigate the biological effects of SW033291 on prostaglandin E2 (PGE2) production, MDSCs were cultured with an ascending concentration of SW033291 from 20 to 1000 nM in both growth medium (GM) and differentiation medium (DM). PGE2 contents in GM and DM were firstly tested, and the result showed that PGE2 was under the detectable level. After MDSCs were incubating in the medium for 24 h, ELISA was used to detect the level of PGE2 in the conditioned medium. The baseline production of PGE2 by MDSCs had no significant difference between GM and DM with a detected concentration of 905.08 ± 225.92 and 952.75 ± 400.15 pg/ml, respectively. The addition of SW033291 increased PGE2 production in a dose-dependent manner without significant difference between DM and GM; significant elevation of approximately 2.8-fold was observed in 100 nM group, reaching 2548.23 ± 341.16 and 2569.22 ± 471.24 pg/ml, followed by 500 nM and 1000 nM group (Fig. 2a). To test the effects of SW033291 on cell senescence, senescence-associated β-galactosidase (SA β-Gal) staining was performed; our results showed that MDSCs treated with different concentration of SW033291 displayed minimal SA β-Gal staining with a cell positive rate around 5%, and there was no significant difference among each treatment group and between GM and DM (Fig. 2b). The cytotoxicity of SW033291 on MDSCs was further evaluated in both GM and DM. As shown in cell viability assay (Fig. 2c, d), no obvious negative effect of SW033291 on MDSC viability was observed with the ascending concentration from 20 to 1000 nM, and the difference was statistically insignificant among various groups and between different culture medium. After 72 h, cell viability in different group significantly increased, which indicated favorable cell proliferation capacity; no significant difference was observed among each group and between different culture medium. The LIVE/DEAD staining was also performed to show that most MDSCs were live (stained as green) in each group after incubating for 24 h; only very few dead cells (stained as red) were found. After 72 h, the number of green MDSCs significantly increased in various groups, showing favorable proliferation capacity, and no significant difference was observed among various groups and between DM and GM (Fig. 2e). Taken together, these data showed that SW033291 increased the production of PGE2 by MDSCs both in GM and DM with the best response reached approximately 2.8-folds increase, and MDSCs were well-tolerated to SW033291 in various concentrations with strong proliferation potential. Reference: Stem Cell Res Ther. 2020 Feb 21;11(1):76. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32085799/ |
| In vivo activity: | To investigate the in vivo muscle regeneration capacity of SW033291, a rat tibialis anterior muscle defected model was created, and the compound was incorporated with MDSCs into fibrin gel to repair the defect by in situ casting. Eighteen muscle defects were randomly allocated into the three groups: (1) gel group, the defect was filled with gel alone; (2) gel/MDSC group, the defect was filled with gel incorporation with MDSCs; and (3) gel/MDSC+SW033291 group, the defect was filled with gel containing 100 nM SW033291 and MDSCs. Four weeks after surgical procedures, the regenerated muscle was evaluated by mechanical measurement and histological examinations. The maximal force produced by the gel group (1700.48 ± 276.39 mN) was significantly lower than those produced by the gel/MDSC group (2448.40 ± 303.79 mN) and gel/MDSC+SW033291 group (3441.42 ± 452.38 mN) (P < 0.001), and no significant difference was observed between the gel/MDSC+SW033291 group and the control limb (3572.26 ± 256.97 mN) (Fig. 6a). The specific forces calculated by normalizing maximal force to muscle mass showed similar trends (Fig. 6b). These results indicated that fibrin gel with or without MDSCs did not fully restore maximum force production to the injured tibialis anterior muscles, and the incorporation of SW033291 dramatically improved functional muscle regeneration to the level as comparable to non-injury muscle. Regenerated muscle tissues were observed in all groups as shown by newly formed myofibers with the nucleus located at the center (Fig. 6c); however, when compared to the gel group (7.00 ± 2.83) and gel/MDSC group (12.67 ± 3.14), significantly increased number of centronucleated myofibers appeared in the HE-stained sections of the gel/MDSC+SW033291 group (26.17 ± 5.95) (P < 0.001) (Fig. 6d). Furthermore, histomorphological analysis showed significantly larger area of regenerated myofibers in the gel/MDSC+SW033291 group (32.02 ± 5.16%) as compared with the gel+MDSC group (19.88 ± 3.57%) and gel group (9.24 ± 2.88%) (P < 0.001) (Fig. 6e). Reference: Stem Cell Res Ther. 2020 Feb 21;11(1):76. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32085799/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 72.70 |
The following data is based on the product molecular weight 412.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Dong Y, Li Y, Zhang C, Chen H, Liu L, Chen S. Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration. Stem Cell Res Ther. 2020 Feb 21;11(1):76. doi: 10.1186/s13287-020-1574-5. PMID: 32085799; PMCID: PMC7035785. 2. Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340. PMID: 26068857; PMCID: PMC4481126. |
| In vivo protocol: | 1. Dong Y, Li Y, Zhang C, Chen H, Liu L, Chen S. Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration. Stem Cell Res Ther. 2020 Feb 21;11(1):76. doi: 10.1186/s13287-020-1574-5. PMID: 32085799; PMCID: PMC7035785. 2. Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340. PMID: 26068857; PMCID: PMC4481126. |
1: Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE,
Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L,
Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C,
Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK,
Markowitz SD. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading
enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun
12;348(6240):aaa2340. doi: 10.1126/science.aaa2340. PubMed PMID: 26068857; PubMed
Central PMCID: PMC4481126.
