SW033291

SW033291
Clinical data
Drug class15-PGDH inhibitor
Identifiers
  • 2-butylsulfinyl-4-phenyl-6-thiophen-2-yl-1-benzothiophen-3-amine
CAS Number
PubChem CID
Chemical and physical data
FormulaC22H21NOS3
Molar mass411.60 g·mol−1
3D model (JSmol)
  • CCCCS(=O)C1=C(C2=C(C=C(C=C2S1)C3=CC=CS3)C4=CC=CC=C4)N
  • InChI=1S/C22H21NOS3/c1-2-3-12-27(24)22-21(23)20-17(15-8-5-4-6-9-15)13-16(14-19(20)26-22)18-10-7-11-25-18/h4-11,13-14H,2-3,12,23H2,1H3
  • Key:KLWRXRJDKBUYCJ-UHFFFAOYSA-N

SW033291 (PGDHi) is a drug which acts as a potent inhibitor of the enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The (R) or (+) enantiomer is more active, though much of the earlier research used the racemic mix. It increases levels of prostaglandin E2 and promotes tissue regeneration, and has shown beneficial effects for numerous potential medical applications in animal studies, including recovery from bone marrow transplant,[1][2][3] acute kidney injury,[4][5] liver damage,[6] diabetes,[7] heart failure,[8][9] cartilage regrowth,[10] sarcopenia,[11][12][13] and neurological conditions such as Alzheimer's disease and traumatic brain injury.[14]

See also

References

  1. ^ Smith JN, Otegbeye F, Jogasuria AP, Christo KF, Antczak MI, Ready JM, et al. (August 2020). "Inhibition of 15-PGDH Protects Mice from Immune-Mediated Bone Marrow Failure". Biology of Blood and Marrow Transplantation. 26 (8): 1552–1556. doi:10.1016/j.bbmt.2020.04.010. PMC 7371522. PMID 32422251.
  2. ^ Smith JN, Dawson DM, Christo KF, Jogasuria AP, Cameron MJ, Antczak MI, et al. (March 2021). "15-PGDH inhibition activates the splenic niche to promote hematopoietic regeneration". JCI Insight. 6 (6) e143658. doi:10.1172/jci.insight.143658. PMC 8026178. PMID 33600377.
  3. ^ Antczak MI, Zhang Y, Wang C, Doran J, Naidoo J, Voruganti S, et al. (May 2017). "Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair". Journal of Medicinal Chemistry. 60 (9): 3979–4001. doi:10.1021/acs.jmedchem.7b00271. PMC 5580352. PMID 28398755.
  4. ^ Miao S, Lv C, Liu Y, Zhao J, Li T, Wang C, et al. (2020). "Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice". Frontiers in Physiology. 11 138. doi:10.3389/fphys.2020.00138. PMC 7082810. PMID 32231583.
  5. ^ Kim BW, Kim HJ, Kim SH, Baik HJ, Kang MS, Kim DH, et al. (December 2021). "15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury". Renal Failure. 43 (1): 168–179. doi:10.1080/0886022X.2020.1870139. PMC 7832987. PMID 33459127.
  6. ^ Shimada H, Yokotobi A, Yamamoto N, Takada M, Kawase A, Nakanishi T, et al. (March 2024). "Inhibition of 15-prostaglandin dehydrogenase attenuates acetaminophen-induced liver injury via suppression of apoptosis in liver endothelial cells". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 202 102640. doi:10.1016/j.plefa.2024.102640. PMID 39217773.
  7. ^ Huang Y, Liang M, Liao Y, Ji Z, Lin W, Pu X, et al. (September 2024). "Investigating the Mechanisms of 15-PGDH Inhibitor SW033291 in Improving Type 2 Diabetes Mellitus: Insights from Metabolomics and Transcriptomics". Metabolites. 14 (9): 509. doi:10.3390/metabo14090509. PMC 11434390. PMID 39330516.
  8. ^ Rubino M, Travers JG, Headrick AL, Enyart BT, Lemieux ME, Cavasin MA, et al. (January 2023). "Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart". Circulation Research. 132 (1): 10–29. doi:10.1161/CIRCRESAHA.122.321475. PMID 36475698.
  9. ^ Zhang L, Wang Q, Guan W (April 2025). "Inhibition of 15-PGDH by SW033291 ameliorates age-related heart failure in mice". Experimental Gerontology. 202 112710. doi:10.1016/j.exger.2025.112710. PMID 39952309.
  10. ^ Singla M, Wang YX, Monti E, Bedi Y, Agarwal P, Su S, et al. (November 2025). "Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration". Science eadx6649. doi:10.1126/science.adx6649. PMID 41308124.
  11. ^ Dong Y, Li Y, Zhang C, Chen H, Liu L, Chen S (February 2020). "Effects of SW033291 on the myogenesis of muscle-derived stem cells and muscle regeneration". Stem Cell Research & Therapy. 11 (1) 76. doi:10.1186/s13287-020-1574-5. PMC 7035785. PMID 32085799.
  12. ^ Wang J, He Y, Wang B, Yin R, Chen B, Wang H (October 2023). "Muscle-targeted nanoparticles strengthen the effects of small-molecule inhibitors in ameliorating sarcopenia". Nanomedicine. 18 (23): 1635–1649. doi:10.2217/nnm-2023-0201. PMID 37909281.
  13. ^ Ahmad SS, Lim JH, Choi I, Lee EJ (December 2024). "Biocomputational screening of natural compounds targeting 15-hydroxyprostaglandin dehydrogenase to improve skeletal muscle during aging". Molecular Diversity. 28 (6): 4425–4439. doi:10.1007/s11030-024-10825-9. PMID 38904907.
  14. ^ Koh Y, Vázquez-Rosa E, Gao F, Li H, Chakraborty S, Tripathi SJ, et al. (May 2025). "Inhibiting 15-PGDH blocks blood-brain barrier deterioration and protects mice from Alzheimer's disease and traumatic brain injury". Proceedings of the National Academy of Sciences of the United States of America. 122 (21) e2417224122. Bibcode:2025PNAS..12217224K. doi:10.1073/pnas.2417224122. PMC 12130856. PMID 40397680.

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