Torin-1 Explained

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]

Notes and References

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

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