The protein product of the MTOR gene (previously been known as FK506-binding protein 12-rapamycin-associated protein 1; FRAP1) is the only member of this kinase subfamily. mTOR is the key enzymatic component of the TORC1 and TORC2 protein complexes. It can act as a Ser/Thr kinase (in both complexes) or a Tyr kinase (in TORC2). The clinically used drugs temsirolimus and everolimus inhibit mTOR kinase activity.

* Key recommended reading is highlighted with an asterisk

* Chen Y, Zhou X. (2020) Research progress of mTOR inhibitors. Eur J Med Chem, 208: 112820. [PMID:32966896]

Hukelmann JL, Anderson KE, Sinclair LV, Grzes KM, Murillo AB, Hawkins PT, Stephens LR, Lamond AI, Cantrell DA. (2016) The cytotoxic T cell proteome and its shaping by the kinase mTOR. Nat Immunol, 17 (1): 104-12. [PMID:26551880]

* Liu GY, Sabatini DM. (2020) mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol, 21 (4): 183-203. [PMID:31937935]

* Saxton RA, Sabatini DM. (2017) mTOR Signaling in Growth, Metabolism, and Disease. Cell, 169 (2): 361-371. [PMID:28388417]

* Xu T, Sun D, Chen Y, Ouyang L. (2020) Targeting mTOR for fighting diseases: A revisited review of mTOR inhibitors. Eur J Med Chem, 199: 112391. [PMID:32416459]

1. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. (2008) Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 4 (11): 691-9. [PMID:18849971]

2. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ et al.. (2012) The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature, 485 (7396): 55-61. [PMID:22367541]

3. Kong F, Zhu T, Yu K, Pagano TG, Desai P, Radebaugh G, Fawzi M. (2011) Isolation and structure of homotemsirolimuses A, B, and C. J Nat Prod, 74 (4): 547-53. [PMID:21438579]

4. Liu KK, Zhu J, Smith GL, Yin MJ, Bailey S, Chen JH, Hu Q, Huang Q, Li C, Li QJ et al.. (2011) Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity. ACS Med Chem Lett, 2 (11): 809-13. [PMID:24900269]

5. Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM et al.. (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. J Med Chem, 53 (19): 7146-55. [PMID:20860370]

6. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K et al.. (2008) Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther, 7 (7): 1851-63. [PMID:18606717]

7. Rivera VM, Squillace RM, Miller D, Berk L, Wardwell SD, Ning Y, Pollock R, Narasimhan NI, Iuliucci JD, Wang F et al.. (2011) Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens. Mol Cancer Ther, 10 (6): 1059-71. [PMID:21482695]

8. Sedrani R, Cottens S, Kallen J, Schuler W. (1998) Chemical modification of rapamycin: the discovery of SDZ RAD. Transplant Proc, 30 (5): 2192-4. [PMID:9723437]

9. Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J et al.. (2011) Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer. J Med Chem, 54 (21): 7579-87. [PMID:21981714]

10. Takeuchi CS, Kim BG, Blazey CM, Ma S, Johnson HW, Anand NK, Arcalas A, Baik TG, Buhr CA, Cannoy J et al.. (2013) Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR). J Med Chem, 56 (6): 2218-34. [PMID:23394126]

11. Venkatesan AM, Dehnhardt CM, Delos Santos E, Chen Z, Dos Santos O, Ayral-Kaloustian S, Khafizova G, Brooijmans N, Mallon R, Hollander I et al.. (2010) Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem, 53 (6): 2636-45. [PMID:20166697]