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Torin-1
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
ChEBI
ChEMBL
CompTox Dashboard ( EPA)
Chemical and physical data
FormulaC35H28F3N5O2
Molar mass607.637 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.


Stub icon

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

Retrieved from " https://en.wikipedia.org/?title=Torin-1&oldid=1203795452"
From Wikipedia, the free encyclopedia
Torin-1
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
ChEBI
ChEMBL
CompTox Dashboard ( EPA)
Chemical and physical data
FormulaC35H28F3N5O2
Molar mass607.637 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.


Stub icon

This pharmacology-related article is a stub. You can help Wikipedia by expanding it.

Retrieved from " https://en.wikipedia.org/?title=Torin-1&oldid=1203795452"

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