Torin-1

Last updated
Torin_1
Torin1 structure.png
Identifiers
  • 1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C35H28F3N5O2
Molar mass 607.637 g·mol−1
3D model (JSmol)
  • CCC(=O)N1CCN(CC1)C2=C(C=C(C=C2)N3C(=O)C=CC4=CN=C5C=CC(=CC5=C43)C6=CC7=CC=CC=C7N=C6)C(F)(F)F
  • InChI=1S/C35H28F3N5O2/c1-2-32(44)42-15-13-41(14-16-42)31-11-9-26(19-28(31)35(36,37)38)43-33(45)12-8-24-20-40-30-10-7-22(18-27(30)34(24)43)25-17-23-5-3-4-6-29(23)39-21-25/h3-12,17-21H,2,13-16H2,1H3
  • Key:AKCRNFFTGXBONI-UHFFFAOYSA-N

Torin_1 is a drug which was one of the first non-rapalog derived inhibitors of the mechanistic target of rapamycin (mTOR) subtypes mTORC1 and mTORC2. [1] [2] [3] In animal studies it has anti-inflammatory, [4] [5] anti-cancer, [6] [7] and anti-aging properties, [8] [9] [10] [11] and shows activity against neuropathic pain. [12] [13] [14]

References

  1. ↑ Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, et al. (October 2010). "Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer". Journal of Medicinal Chemistry. 53 (19): 7146–55. doi:10.1021/jm101144f. PMC   3893826 . PMID   20860370.
  2. ↑ Schenone S, Brullo C, Musumeci F, Radi M, Botta M (2011). "ATP-competitive inhibitors of mTOR: an update". Current Medicinal Chemistry. 18 (20): 2995–3014. doi:10.2174/092986711796391651. hdl: 11381/2432251 . PMID   21651476.
  3. ↑ Liu Q, Kang SA, Thoreen CC, Hur W, Wang J, Chang JW, et al. (2012). "Development of ATP-Competitive mTOR Inhibitors". MTOR. Methods in Molecular Biology. Vol. 821. pp. 447–60. doi:10.1007/978-1-61779-430-8_29. ISBN   978-1-61779-429-2. PMC   3964610 . PMID   22125084.
  4. ↑ Weichhart T, Haidinger M, Katholnig K, Kopecky C, Poglitsch M, Lassnig C, et al. (April 2011). "Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells". Blood. 117 (16): 4273–83. doi: 10.1182/blood-2010-09-310888 . PMID   21368289. S2CID   14845187.
  5. ↑ Patel AB, Theoharides TC (June 2017). "Methoxyluteolin Inhibits Neuropeptide-stimulated Proinflammatory Mediator Release via mTOR Activation from Human Mast Cells". The Journal of Pharmacology and Experimental Therapeutics. 361 (3): 462–471. doi:10.1124/jpet.117.240564. PMID   28404689. S2CID   11750159.
  6. ↑ Francipane MG, Lagasse E (November 2013). "Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1". Oncotarget. 4 (11): 1948–62. doi:10.18632/oncotarget.1310. PMC   3875761 . PMID   24185040.
  7. ↑ Jhanwar-Uniyal M, Gillick JL, Neil J, Tobias M, Thwing ZE, Murali R (January 2015). "Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes". Advances in Biological Regulation. 57: 64–74. doi:10.1016/j.jbior.2014.09.004. PMID   25442674.
  8. ↑ Leontieva OV, Demidenko ZN, Blagosklonny MV (September 2015). "Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program)". Oncotarget. 6 (27): 23238–48. doi:10.18632/oncotarget.4836. PMC   4695114 . PMID   26177051.
  9. ↑ Leontieva OV, Blagosklonny MV (December 2016). "Gerosuppression by pan-mTOR inhibitors". Aging. 8 (12): 3535–3551. doi:10.18632/aging.101155. PMC   5270685 . PMID   28077803.
  10. ↑ Mason JS, Wileman T, Chapman T (2018). "Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster". PLOS ONE. 13 (1) e0190105. Bibcode:2018PLoSO..1390105M. doi: 10.1371/journal.pone.0190105 . PMC   5766080 . PMID   29329306.
  11. ↑ Kucheryavenko O, Nelson G, von Zglinicki T, Korolchuk VI, Carroll B (June 2019). "The mTORC1-autophagy pathway is a target for senescent cell elimination". Biogerontology. 20 (3): 331–335. doi:10.1007/s10522-019-09802-9. PMC   6535413 . PMID   30798505.
  12. ↑ Obara I, Tochiki KK, Géranton SM, Carr FB, Lumb BM, Liu Q, Hunt SP (November 2011). "Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice". Pain. 152 (11): 2582–95. doi:10.1016/j.pain.2011.07.025. PMID   21917376. S2CID   207309453.
  13. ↑ Choi S, Kim K, Cha M, Kim M, Lee BH (January 2020). "mTOR signaling intervention by Torin1 and XL388 in the insular cortex alleviates neuropathic pain" (PDF). Neuroscience Letters. 718 134742. doi: 10.1016/j.neulet.2020.134742 . PMID   31917234. S2CID   209898631.
  14. ↑ Kim K, Choi S, Cha M, Lee BH (April 2020). "Effects of mTOR inhibitors on neuropathic pain revealed by optical imaging of the insular cortex in rats" (PDF). Brain Research. 1733 146720. doi: 10.1016/j.brainres.2020.146720 . PMID   32061737. S2CID   211105385.


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