Torin-1: Difference between revisions

Torin-1
Identifiers
	IUPAC name 1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one;
CAS Number	1222998-36-8;
PubChem CID	49836027;
CompTox Dashboard (EPA)	DTXSID40678621 ;
Chemical and physical data
Formula	C35H28F3N5O2
Molar mass	607.637 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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;

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Revision as of 01:17, 26 December 2020

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] anti-cancer,^[5]^[6] and anti-aging properties,^[7]^[8]^[9]^[10] and shows activity against neuropathic pain.^[11]^[12]^[13]

References

^ Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS. 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. J Med Chem. 2010 Oct 14;53(19):7146-55. doi:10.1021/jm101144f PMID 20860370
^ Schenone S, Brullo C, Musumeci F, Radi M, Botta M. ATP-competitive inhibitors of mTOR: an update. Curr Med Chem. 2011;18(20):2995-3014. doi:10.2174/092986711796391651 PMID 21651476
^ 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. Methods Mol Biol. 2012;821:447-60. doi:10.1007/978-1-61779-430-8_29 PMID 22125084
^ Weichhart T, Haidinger M, Katholnig K, Kopecky C, Poglitsch M, Lassnig C, Rosner M, Zlabinger GJ, Hengstschläger M, Müller M, Hörl WH, Säemann MD. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood. 2011 Apr 21;117(16):4273-83. doi:10.1182/blood-2010-09-310888 PMID 21368289
^ Francipane MG, Lagasse E. Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1. Oncotarget. 2013 Nov;4(11):1948-62. doi:10.18632/oncotarget.1310 PMID 24185040
^ 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. Adv Biol Regul. 2015 Jan;57:64-74. doi:10.1016/j.jbior.2014.09.004 PMID 25442674
^ Leontieva OV, Demidenko ZN, Blagosklonny MV. Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program). Oncotarget. 2015 Sep 15;6(27):23238-48. doi:10.18632/oncotarget.4836 PMID 26177051
^ Leontieva OV, Blagosklonny MV. Gerosuppression by pan-mTOR inhibitors. Aging (Albany NY). 2016 Dec 30;8(12):3535-3551. doi:10.18632/aging.101155 PMID 28077803
^ 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 Jan 12;13(1):e0190105. doi:10.1371/journal.pone.0190105 PMID 29329306
^ Kucheryavenko O, Nelson G, von Zglinicki T, Korolchuk VI, Carroll B. The mTORC1-autophagy pathway is a target for senescent cell elimination. Biogerontology. 2019 Jun;20(3):331-335. doi:10.1007/s10522-019-09802-9 {{pmid|30798505]]
^ 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. 2011 Nov;152(11):2582-95. doi:10.1016/j.pain.2011.07.025 PMID 21917376
^ Choi S, Kim K, Cha M, Kim M, Lee BH. mTOR signaling intervention by Torin1 and XL388 in the insular cortex alleviates neuropathic pain. Neurosci Lett. 2020 Jan 23;718:134742. doi:10.1016/j.neulet.2020.134742 PMID 31917234
^ 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 Res. 2020 Apr 15;1733:146720. doi:10.1016/j.brainres.2020.146720 PMID 32061737

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[1] Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS. 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. J Med Chem. 2010 Oct 14;53(19):7146-55. doi:10.1021/jm101144f PMID 20860370

[2] Schenone S, Brullo C, Musumeci F, Radi M, Botta M. ATP-competitive inhibitors of mTOR: an update. Curr Med Chem. 2011;18(20):2995-3014. doi:10.2174/092986711796391651 PMID 21651476

[3] 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. Methods Mol Biol. 2012;821:447-60. doi:10.1007/978-1-61779-430-8_29 PMID 22125084

[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. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood. 2011 Apr 21;117(16):4273-83. doi:10.1182/blood-2010-09-310888 PMID 21368289

[5] Francipane MG, Lagasse E. Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1. Oncotarget. 2013 Nov;4(11):1948-62. doi:10.18632/oncotarget.1310 PMID 24185040

[6] 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. Adv Biol Regul. 2015 Jan;57:64-74. doi:10.1016/j.jbior.2014.09.004 PMID 25442674

[7] Leontieva OV, Demidenko ZN, Blagosklonny MV. Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program). Oncotarget. 2015 Sep 15;6(27):23238-48. doi:10.18632/oncotarget.4836 PMID 26177051

[8] Leontieva OV, Blagosklonny MV. Gerosuppression by pan-mTOR inhibitors. Aging (Albany NY). 2016 Dec 30;8(12):3535-3551. doi:10.18632/aging.101155 PMID 28077803

[9] 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 Jan 12;13(1):e0190105. doi:10.1371/journal.pone.0190105 PMID 29329306

[10] Kucheryavenko O, Nelson G, von Zglinicki T, Korolchuk VI, Carroll B. The mTORC1-autophagy pathway is a target for senescent cell elimination. Biogerontology. 2019 Jun;20(3):331-335. doi:10.1007/s10522-019-09802-9 {{pmid|30798505]]

[11] 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. 2011 Nov;152(11):2582-95. doi:10.1016/j.pain.2011.07.025 PMID 21917376

[12] Choi S, Kim K, Cha M, Kim M, Lee BH. mTOR signaling intervention by Torin1 and XL388 in the insular cortex alleviates neuropathic pain. Neurosci Lett. 2020 Jan 23;718:134742. doi:10.1016/j.neulet.2020.134742 PMID 31917234

[13] 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 Res. 2020 Apr 15;1733:146720. doi:10.1016/j.brainres.2020.146720 PMID 32061737

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