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IU1

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IU1
Identifiers
  • 1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-2-pyrrolidin-1-ylethanone
CAS Number
PubChem CID
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H21FN2O
Molar mass300.377 g·mol−1
3D model (JSmol)
  • CC1=CC(=C(N1C2=CC=C(C=C2)F)C)C(=O)CN3CCCC3
  • InChI=1S/C18H21FN2O/c1-13-11-17(18(22)12-20-9-3-4-10-20)14(2)21(13)16-7-5-15(19)6-8-16/h5-8,11H,3-4,9-10,12H2,1-2H3
  • Key:JUWDSDKJBMFLHE-UHFFFAOYSA-N

IU1 is a drug used in scientific research which acts as a selective inhibitor of the ubiquitin-specific processing protease enzyme USP14.[1] It is of interest in anti-cancer and antiviral research and also as a potential anti-aging drug. Numerous derivatives of IU1 have been developed with up to 10x the potency of IU1 as USP14 inhibitors,[2][3] but IU1 remains the most widely used compound in research in this area.[4][5][6][7][8][9][10]

References

[edit]
  1. ^ Lee BH, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC, et al. (September 2010). "Enhancement of proteasome activity by a small-molecule inhibitor of USP14". Nature. 467 (7312): 179–84. Bibcode:2010Natur.467..179L. doi:10.1038/nature09299. PMC 2939003. PMID 20829789.
  2. ^ Wang Y, Jiang Y, Ding S, Li J, Song N, Ren Y, et al. (December 2018). "Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade". Cell Research. 28 (12): 1186–1194. doi:10.1038/s41422-018-0091-x. PMC 6274642. PMID 30254335.
  3. ^ Boselli M, Lee BH, Robert J, Prado MA, Min SW, Cheng C, et al. (November 2017). "An inhibitor of the proteasomal deubiquitinating enzyme USP14 induces tau elimination in cultured neurons". The Journal of Biological Chemistry. 292 (47): 19209–19225. doi:10.1074/jbc.M117.815126. PMC 5702663. PMID 28972160.
  4. ^ Nag DK, Finley D (April 2012). "A small-molecule inhibitor of deubiquitinating enzyme USP14 inhibits Dengue virus replication". Virus Research. 165 (1): 103–106. doi:10.1016/j.virusres.2012.01.009. PMID 22306365.
  5. ^ Moon S, Muniyappan S, Lee SB, Lee BH (June 2021). "Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases". International Journal of Molecular Sciences. 22 (12): 6213. doi:10.3390/ijms22126213. PMC 8226605. PMID 34207520.
  6. ^ Wang F, Ning S, Yu B, Wang Y (2022). "USP14: Structure, Function, and Target Inhibition". Frontiers in Pharmacology. 12 801328. doi:10.3389/fphar.2021.801328. PMC 8766727. PMID 35069211.
  7. ^ Pan J, Zhao J, Feng L, Xu X, He Z, Liang W (March 2023). "Inhibition of USP14 Suppresses ROS-dependent Ferroptosis and Alleviates Renal Ischemia/Reperfusion Injury". Cell Biochemistry and Biophysics. 81 (1): 87–96. doi:10.1007/s12013-022-01107-y. PMID 36255562.
  8. ^ Hou W, Yao J, Liu J, Lin X, Wei J, Yin X, et al. (November 2023). "USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice". CNS Neuroscience & Therapeutics. 29 (11): 3612–3623. doi:10.1111/cns.14292. PMC 10580339. PMID 37269080.
  9. ^ Lim JJ, Noh S, Kang W, Hyun B, Lee BH, Hyun S (December 2024). "Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner". Autophagy. 20 (12): 2752–2768. doi:10.1080/15548627.2024.2389607. PMC 11587835. PMID 39113571.
  10. ^ Zhou X, Xia Q, Wang B, Li J, Liu B, Wang S, et al. (2025). "USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5". Theranostics. 15 (6): 2293–2314. doi:10.7150/thno.103629. PMC 11840735. PMID 39990235.


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