Torin-1

{{Short description|Chemical compound}}

{{Drugbox

| drug_name = Torin_1

| IUPAC_name = 1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one

| image = Torin1_structure.png

| tradename =

| legal_US =

| legal_status =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number = 1222998-36-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = K9HTV88VQZ

| PubChem = 49836027

| ChemSpiderID = 26232175

| ChEMBL = 1256459

| ChEBI = 84327

| C = 35

| H = 28

| F = 3

| N = 5

| O = 2

| 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

| StdInChI = 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

| StdInChIKey = 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.{{cite journal | vauthors = Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 53 | issue = 19 | pages = 7146–55 | date = October 2010 | pmid = 20860370 | doi = 10.1021/jm101144f | pmc = 3893826 }}{{cite journal | vauthors = Schenone S, Brullo C, Musumeci F, Radi M, Botta M | title = ATP-competitive inhibitors of mTOR: an update | journal = Current Medicinal Chemistry | year = 2011 | volume = 18 | issue = 20 | pages = 2995–3014 | pmid = 21651476 | doi = 10.2174/092986711796391651 | hdl = 11381/2432251 | hdl-access = free }}{{cite book | vauthors = Liu Q, Kang SA, Thoreen CC, Hur W, Wang J, Chang JW, Markhard A, Zhang J, Sim T, Sabatini DM, Gray NS | chapter = Development of ATP-Competitive mTOR Inhibitors | title = MTOR | display-authors = 6 | series = Methods in Molecular Biology | year = 2012 | volume = 821 | pages = 447–60 | pmid = 22125084 | doi = 10.1007/978-1-61779-430-8_29 | pmc = 3964610 | isbn = 978-1-61779-429-2 }} In animal studies it has anti-inflammatory,{{cite journal | vauthors = Weichhart T, Haidinger M, Katholnig K, Kopecky C, Poglitsch M, Lassnig C, Rosner M, Zlabinger GJ, Hengstschläger M, Müller M, Hörl WH, Säemann MD | display-authors = 6 | title = Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells | journal = Blood | volume = 117 | issue = 16 | pages = 4273–83 | date = April 2011 | pmid = 21368289 | doi = 10.1182/blood-2010-09-310888 | s2cid = 14845187 | doi-access = free }}{{cite journal | vauthors = Patel AB, Theoharides TC | title = Methoxyluteolin Inhibits Neuropeptide-stimulated Proinflammatory Mediator Release via mTOR Activation from Human Mast Cells | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 361 | issue = 3 | pages = 462–471 | date = June 2017 | pmid = 28404689 | doi = 10.1124/jpet.117.240564 | s2cid = 11750159 | doi-access = }} anti-cancer,{{cite journal | vauthors = Francipane MG, Lagasse E | title = Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1 | journal = Oncotarget | volume = 4 | issue = 11 | pages = 1948–62 | date = November 2013 | pmid = 24185040 | doi = 10.18632/oncotarget.1310 | pmc = 3875761 }}{{cite journal | vauthors = Jhanwar-Uniyal M, Gillick JL, Neil J, Tobias M, Thwing ZE, Murali R | title = Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes | journal = Advances in Biological Regulation | volume = 57 | pages = 64–74 | date = January 2015 | pmid = 25442674 | doi = 10.1016/j.jbior.2014.09.004 }} and anti-aging properties,{{cite journal | vauthors = Leontieva OV, Demidenko ZN, Blagosklonny MV | title = Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program) | journal = Oncotarget | volume = 6 | issue = 27 | pages = 23238–48 | date = September 2015 | pmid = 26177051 | doi = 10.18632/oncotarget.4836 | pmc = 4695114 }}{{cite journal | vauthors = Leontieva OV, Blagosklonny MV | title = Gerosuppression by pan-mTOR inhibitors | journal = Aging | volume = 8 | issue = 12 | pages = 3535–3551 | date = December 2016 | pmid = 28077803 | doi = 10.18632/aging.101155 | pmc = 5270685 }}{{cite journal | vauthors = Mason JS, Wileman T, Chapman T | title = Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster | journal = PLOS ONE | year = 2018 | volume = 13 | issue = 1 | pages = e0190105 | pmid = 29329306 | doi = 10.1371/journal.pone.0190105 | pmc = 5766080 | bibcode = 2018PLoSO..1390105M | doi-access = free }}{{cite journal | vauthors = Kucheryavenko O, Nelson G, von Zglinicki T, Korolchuk VI, Carroll B | title = The mTORC1-autophagy pathway is a target for senescent cell elimination | journal = Biogerontology | volume = 20 | issue = 3 | pages = 331–335 | date = June 2019 | pmid = 30798505 | doi = 10.1007/s10522-019-09802-9 | pmc = 6535413 }} and shows activity against neuropathic pain.{{cite journal | vauthors = Obara I, Tochiki KK, Géranton SM, Carr FB, Lumb BM, Liu Q, Hunt SP | title = Systemic inhibition of the mammalian target of rapamycin (mTOR) pathway reduces neuropathic pain in mice | journal = Pain | volume = 152 | issue = 11 | pages = 2582–95 | date = November 2011 | pmid = 21917376 | doi = 10.1016/j.pain.2011.07.025 | s2cid = 207309453 }}{{cite journal | vauthors = Choi S, Kim K, Cha M, Kim M, Lee BH | title = mTOR signaling intervention by Torin1 and XL388 in the insular cortex alleviates neuropathic pain | journal = Neuroscience Letters | volume = 718 | pages = 134742 | date = January 2020 | pmid = 31917234 | doi = 10.1016/j.neulet.2020.134742 | s2cid = 209898631 | doi-access = free | url = https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/175493/1/T202000432.pdf }}{{cite journal | vauthors = Kim K, Choi S, Cha M, Lee BH | title = Effects of mTOR inhibitors on neuropathic pain revealed by optical imaging of the insular cortex in rats | journal = Brain Research | volume = 1733 | pages = 146720 | date = April 2020 | pmid = 32061737 | doi = 10.1016/j.brainres.2020.146720 | s2cid = 211105385 | doi-access = free | url = https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/175518/1/T202000481.pdf }}