LE135

LE135
Identifiers
  • 4-(5,7,7,10,10-pentamethyl-8,9-dihydronaphtho[2,3-b][1,4]benzodiazepin-13-yl)benzoic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC29H30N2O2
Molar mass438.571 g·mol−1
3D model (JSmol)
  • CC1(CCC(C2=CC3=C(C=C21)N=C(C4=CC=CC=C4N3C)C5=CC=C(C=C5)C(=O)O)(C)C)C
  • InChI=1S/C29H30N2O2/c1-28(2)14-15-29(3,4)22-17-25-23(16-21(22)28)30-26(18-10-12-19(13-11-18)27(32)33)20-8-6-7-9-24(20)31(25)5/h6-13,16-17H,14-15H2,1-5H3,(H,32,33)
  • Key:YZZAIQOVMHVWBS-UHFFFAOYSA-N

LE135 is a drug which acts as a selective retinoic acid receptor β (RARβ) antagonist. It was developed in the 1990s and has been widely used for research into the function of RARβ especially its roles in cell differentiation during growth, tissue repair and embryonic development, regulation of immune system function, and development of certain forms of cancer.[1][2][3][4][5][6][7][8][9][10][11][12][13] However, it has also been shown to act as a potent activator of the cation channels TRPV1 and TRPA1, which means caution must be applied when interpreting results which assume that it is only acting by blocking RARβ.[14]

References

  1. ^ Umemiya H, Fukasawa H, Ebisawa M, Eyrolles L, Kawachi E, Eisenmann G, et al. (19 December 1997). "Regulation of retinoidal actions by diazepinylbenzoic acids". Retinoid Synergists Which Activate the RXR-RAR Heterodimers. J Med Chem. 40 (26): 4222–4234. doi:10.1021/jm9704309. PMID 9435893.
  2. ^ Kagechika H, Kawachi E, Fukasawa H, Saito G, Iwanami N, Umemiya H, et al. (13 February 1997). "Inhibition of IL-1-induced IL-6 production by synthetic retinoids". Biochemical and Biophysical Research Communications. 231 (2): 243–248. doi:10.1006/bbrc.1997.6087. PMID 9070257.
  3. ^ Jimi S, Shono T, Tanaka M, Kono A, Yamada Y, Shudo K, et al. (1998). "Effect of retinoic acid on morphological changes of human pancreatic cancer cells on collagen gels: a possible association with the metastatic potentials". Oncology Research. 10 (1): 7–14. PMID 9613452.
  4. ^ Kagechika H (March 2002). "Novel synthetic retinoids and separation of the pleiotropic retinoidal activities". Current Medicinal Chemistry. 9 (5): 591–608. doi:10.2174/0929867024606975. PMID 11945126.
  5. ^ Iwata M, Eshima Y, Kagechika H (August 2003). "Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors". International Immunology. 15 (8): 1017–1025. doi:10.1093/intimm/dxg101. PMID 12882839.
  6. ^ Kafienah W, Mistry S, Perry MJ, Politopoulou G, Hollander AP (October 2007). "Pharmacological regulation of adult stem cells: chondrogenesis can be induced using a synthetic inhibitor of the retinoic acid receptor". Stem Cells. 25 (10). Dayton, Ohio: 2460–2468. doi:10.1634/stemcells.2007-0059. PMID 17615267.
  7. ^ Gong M, Bi Y, Jiang W, Zhang Y, Chen L, Hou N, et al. (April 2013). "Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation". The International Journal of Biochemistry & Cell Biology. 45 (4): 866–875. doi:10.1016/j.biocel.2013.01.002. PMID 23318218.
  8. ^ Rothwell CM, Spencer GE (October 2014). "Retinoid signaling is necessary for, and promotes long-term memory formation following operant conditioning". Neurobiology of Learning and Memory. 114: 127–140. doi:10.1016/j.nlm.2014.05.010. PMID 24925874.
  9. ^ Lee HR, Shin HK, Park SY, Kim HY, Lee WS, Rhim BY, et al. (November 2014). "Cilostazol suppresses β-amyloid production by activating a disintegrin and metalloproteinase 10 via the upregulation of SIRT1-coupled retinoic acid receptor-β". Journal of Neuroscience Research. 92 (11): 1581–1590. doi:10.1002/jnr.23421. PMID 24903973.
  10. ^ Gao Z, Huo L, Cui D, Yang X, Zeng J (11 March 2016). "The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells". PLOS ONE. 11 (3) e0150831. doi:10.1371/journal.pone.0150831. PMC 4788292. PMID 26967733.
  11. ^ le Maire A, Teyssier C, Balaguer P, Bourguet W, Germain P (5 November 2019). "Regulation of RXR-RAR Heterodimers by RXR- and RAR-Specific Ligands and Their Combinations". Cells. 8 (11): 1392. doi:10.3390/cells8111392. PMC 6912802. PMID 31694317.
  12. ^ Wang S, Bi W, Liu Y, Cheng J, Sun W, Wu G, et al. (22 January 2020). "The Antagonist of Retinoic Acid Receptor α, ER-50891 Antagonizes the Inhibitive Effect of All-Trans Retinoic Acid and Rescues Bone Morphogenetic Protein 2-Induced Osteoblastogenic Differentiation". Drug Design, Development and Therapy. 14: 297–308. doi:10.2147/DDDT.S215786. PMC 6985983. PMID 32158187.
  13. ^ Lee NH, Choi MJ, Ji SM, Kwak HJ, Cheon HG (26 March 2026). "Adapalene, an RAR agonist, exerts anti-inflammatory effects by regulating macrophage polarization through RAR-mediated signaling pathways". Scientific Reports. 16 (1) 11385. doi:10.1038/s41598-026-44454-z. PMC 13049118. PMID 41888273.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  14. ^ Yin S, Luo J, Qian A, Yu W, Hu H (March 2014). "LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels". British Journal of Pharmacology. 171 (6): 1510–1520. doi:10.1111/bph.12543. PMC 3954489. PMID 24308840.
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