GSK484

Last updated

GSK484
GSK484.svg
Identifiers
  • [(3S,4R)-3-amino-4-hydroxypiperidin-1-yl]-[2-[1-(cyclopropylmethyl)indol-2-yl]-7-methoxy-1-methylbenzimidazol-5-yl]methanone
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
Formula C27H31N5O3
Molar mass 473.577 g·mol−1
3D model (JSmol)
  • CN1C2=C(C=C(C=C2OC)C(=O)N3CC[C@H]([C@H](C3)N)O)N=C1C4=CC5=CC=CC=C5N4CC6CC6
  • InChI=1S/C27H31N5O3/c1-30-25-20(11-18(13-24(25)35-2)27(34)31-10-9-23(33)19(28)15-31)29-26(30)22-12-17-5-3-4-6-21(17)32(22)14-16-7-8-16/h3-6,11-13,16,19,23,33H,7-10,14-15,28H2,1-2H3/t19-,23+/m0/s1
  • Key:BDYDINKSILYBOL-WMZHIEFXSA-N

GSK484 is an experimental drug which acts as a selective inhibitor of the enzyme peptidylarginine deiminase 4 (PAD4). It has antiinflammatory effects and has been researched for potential use in the treatment of various inflammatory conditions, primarily rheumatoid arthritis, but it has also been used to investigate the role of PAD4 in acute kidney injury, lung inflammation, heart muscle damage following heart attack, osteoporosis, diabetes, and some forms of cancer. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]

See also

References

  1. ↑ Koushik S, Joshi N, Nagaraju S, Mahmood S, Mudeenahally K, Padmavathy R, et al. (April 2017). "PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis". Expert Opinion on Therapeutic Targets. 21 (4): 433–447. doi:10.1080/14728222.2017.1294160. PMID   28281906.
  2. ↑ Cedervall J, Dragomir A, Saupe F, Zhang Y, Ärnlöv J, Larsson E, et al. (2017). "Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice". Oncoimmunology. 6 (8): e1320009. doi:10.1080/2162402X.2017.1320009. PMC   5593702 . PMID   28919990.{{cite journal}}: CS1 maint: article number as page number (link)
  3. ↑ Mondal S, Thompson PR (March 2019). "Protein Arginine Deiminases (PADs): Biochemistry and Chemical Biology of Protein Citrullination". Accounts of Chemical Research. 52 (3): 818–832. doi:10.1021/acs.accounts.9b00024. PMC   6443095 . PMID   30844238.
  4. ↑ Du M, Yang W, Schmull S, Gu J, Xue S (January 2020). "Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction". International Immunopharmacology. 78 106055. doi:10.1016/j.intimp.2019.106055. PMID   31816575.
  5. ↑ Du M, Yang L, Gu J, Wu J, Ma Y, Wang T (2020). "Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury". Mediators of Inflammation. 2020: 1724206. doi: 10.1155/2020/1724206 . PMC   7787741 . PMID   33456369.{{cite journal}}: CS1 maint: article number as page number (link)
  6. ↑ Hu Z, Hua X, Mo X, Chang Y, Chen X, Xu Z, et al. (July 2023). "Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis". iScience. 26 (7) 107162. Bibcode:2023iSci...26j7162H. doi:10.1016/j.isci.2023.107162. PMC   10391931 . PMID   37534129.
  7. ↑ Wang B, Su X, Zhang B, Pan S (September 2023). "GSK484, an inhibitor of peptidyl arginine deiminase 4, increases the radiosensitivity of colorectal cancer and inhibits neutrophil extracellular traps". The Journal of Gene Medicine. 25 (9) e3530. doi:10.1002/jgm.3530. PMID   37203323.
  8. ↑ Salzmann M, Gibler P, Haider P, Brekalo M, Plasenzotti R, Filip T, et al. (January 2024). "Neutrophil extracellular traps induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model". Journal of Thrombosis and Haemostasis. 22 (1): 188–198. doi: 10.1016/j.jtha.2023.09.014 . PMID   37748582.
  9. ↑ Guo Y, Zhou H, Wang Y, Gu Y (March 2025). "Activated NETosis of bone marrow neutrophils up-regulates macrophage osteoclastogenesis via cGAS-STING/AKT2 pathway to promote osteoporosis". Experimental Cell Research. 446 (2) 114477. doi:10.1016/j.yexcr.2025.114477. PMID   39988126.
  10. ↑ Floyd JL, Prasad R, Dupont MD, Adu-Rutledge Y, Anshumali S, Paul S, et al. (April 2025). "Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes". Diabetologia. 68 (4): 866–889. doi:10.1007/s00125-024-06349-4. PMC   11950064 . PMID   39875729.
  11. ↑ Lu Z, Zhu L, Yi C, Su B, Wang R (December 2025). "C5a/C5aR regulates Th1/Th2 imbalance in sepsis-associated lung injury by promoting neutrophil activation to increase PAD4 expression". Annals of Medicine. 57 (1) 2447406. doi:10.1080/07853890.2024.2447406. PMC   11749016 . PMID   39831526.
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