mechanistic target of rapamycin kinase | FRAP subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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mechanistic target of rapamycin kinase

Target not currently curated in GtoImmuPdb

Target id: 2109

Nomenclature: mechanistic target of rapamycin kinase

Abbreviated Name: mTOR

Family: FRAP subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2549 1p36 MTOR mechanistic target of rapamycin kinase
Mouse - 2549 4 E1 Mtor mechanistic target of rapamycin kinase
Rat - 2549 5 q36 Mtor mechanistic target of rapamycin kinase
Previous and Unofficial Names
FK506 binding protein 12-rapamycin associated protein 2 | FKBP12-rapamycin complex-associated protein 1 | FKBP-rapamycin associated protein | FKBP-rapamycin-associated protein FRAP | RAFT1 | rapamycin and FKBP12 target 1 | rapamycin associated protein FRAP2 | rapamycin target protein 1 | RAPT1 | mammalian target of rapamycin | FK506 binding protein 12-rapamycin associated protein 1 | mechanistic target of rapamycin (serine/threonine kinase) | mechanistic target of rapamycin
Database Links
BRENDA
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Co-crystal structure of the PPIase domain of FKBP51, Rapamycin and the FRB fragment of mTOR
PDB Id:  4DRI
Resolution:  1.45Å
Species:  Human
References:  24
Image of receptor 3D structure from RCSB PDB
Description:  The solution structure of the rapamycin-binding domain of mTOR (FRB)
PDB Id:  2NPU
Resolution:  0.0Å
Species:  Human
References:  36
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of PI3K-gamma in complex with benzothiazole 82.
PDB Id:  3QK0
Ligand:  compound 82 [PMID: 21332118]
Resolution:  2.85Å
Species:  Human
References:  5
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
PQR620 Hs Inhibition 9.6 pKd 27
pKd 9.6 (Kd 2.7x10-10 M) [27]
Description: Binding affinity constant.
neolymphostin A Hs Inhibition 8.0 pKd 4
pKd 8.0 (Kd 1x10-8 M) [4]
Description: Determined using an active-site dependent competition binding assay.
bimiralisib Hs Inhibition 7.9 pKd
pKd 7.9 (Kd 1.2x10-8 M)
wortmannin Hs Inhibition 5.0 pKd 4
pKd 5.0 (Kd 9.2x10-6 M) [4]
sapanisertib Hs Inhibition 8.9 pKi 14
pKi 8.9 (Ki 1.4x10-9 M) [14]
compound 82 [PMID: 21332118] Hs Inhibition 8.7 pKi 5
pKi 8.7 (Ki 2x10-9 M) [5]
PQR620 Hs Inhibition 8.0 pKi 27
pKi 8.0 (Ki 1.08x10-8 M) [27]
Description: In vitro inhibition constant.
PF-04691502 Hs Inhibition 7.8 pKi 19
pKi 7.8 (Ki 1.6x10-8 M) [19]
apitolisib Hs Inhibition 7.8 pKi 33
pKi 7.8 (Ki 1.7x10-8 M) [33]
omipalisib Hs Inhibition 6.5 – 6.7 pKi 16
pKi 6.5 – 6.7 (Ki 3x10-7 – 1.8x10-7 M) [16]
berzosertib Hs Inhibition <6.0 pKi 7
pKi <6.0 (Ki >1x10-6 M) [7]
eCF309 Hs Inhibition 8.1 pEC50 8
pEC50 8.1 (EC50 9x10-9 M) [8]
Description: In a cell viability assay.
ridaforolimus Hs Inhibition 9.7 pIC50 30
pIC50 9.7 (IC50 2x10-10 M) [30]
Description: Measured as dose-dependent inhibition of phosphorylation of ribosomal protein S6, a signaling protein downstream of mTOR
torin 1 Hs Inhibition 9.5 pIC50 20
pIC50 9.5 (IC50 2.9x10-10 M) [20]
Description: Assayed using mTORC1 complex
AZD8055 Hs Inhibition 9.1 pIC50 26
pIC50 9.1 (IC50 8x10-10 M) [26]
sapanisertib Hs Inhibition 9.0 pIC50 14
pIC50 9.0 (IC50 1x10-9 M) [14]
gedatolisib Hs Inhibition 8.8 pIC50 35
pIC50 8.8 (IC50 1.6x10-9 M) [35]
everolimus Hs Inhibition 8.7 pIC50 32
pIC50 8.7 (IC50 2x10-9 M) [32]
vistusertib Hs Inhibition 8.6 pIC50 26
pIC50 8.6 (IC50 2.8x10-9 M) [26]
Description: Assay using FLAG-tagged human mTOR(1362-2549)
torin 2 Hs Inhibition 8.6 pIC50 21
pIC50 8.6 (IC50 2.81x10-9 M) [21]
panulisib Hs Inhibition 8.4 pIC50 15
pIC50 8.4 (IC50 4.4x10-9 M) [15]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
WYE-354 Hs Inhibition 8.3 pIC50 38
pIC50 8.3 (IC50 5x10-9 M) [38]
Description: DELFIA assay measuring His6-S6K1 T389 phosphorylation.
dactolisib Hs Inhibition 8.2 pIC50 22
pIC50 8.2 (IC50 6x10-9 M) [22]
Description: Measured as inhibition of downstream mTOR activated p70S6K
PP-242 Hs Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8x10-9 M) [1]
CZ415 Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 8.51x10-9 M) [3]
Description: Assessed in a competition binding assay using a mixed inhibitor lipid kinase matrix.
XL388 Hs Inhibition 8.0 pIC50 34
pIC50 8.0 (IC50 9.9x10-9 M) [34]
PP121 Hs Inhibition 8.0 pIC50 1
pIC50 8.0 (IC50 1x10-8 M) [1]
CC-223 Hs Inhibition 8.0 pIC50 23
pIC50 8.0 (IC50 1x10-8 M) [23]
KU-0063794 Hs Inhibition 8.0 pIC50 10
pIC50 8.0 (IC50 1x10-8 M) [10]
Description: Inhibition of immunoprecipitated mTORC1 (S6K1 as substrate) and mTORC2 (Akt as substrate).
eCF309 Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.5x10-8 M) [8]
Description: In a biochemical assys using recombinant wild type enzyme.
PI-103 Hs Inhibition 7.5 pIC50 28
pIC50 7.5 (IC50 3x10-8 M) [28]
VS-5584 Hs Inhibition 7.4 pIC50 12
pIC50 7.4 (IC50 3.7x10-8 M) [12]
compound 11j [PMID: 23021994] Hs Inhibition 7.3 pIC50 11
pIC50 7.3 (IC50 5x10-8 M) [11]
GDC0084 Hs Inhibition 7.2 pIC50 13
pIC50 7.2 (IC50 7x10-8 M) [13]
LY3023414 Hs Inhibition 6.8 pIC50 2
pIC50 6.8 (IC50 1.65x10-7 M) [2]
temsirolimus Hs Inhibition 5.8 pIC50 17
pIC50 5.8 (IC50 1.76x10-6 M) [17]
MEN1611 Hs Inhibition 5.8 pIC50 25
pIC50 5.8 (IC50 1.6x10-6 M) [25]
STK16-IN-1 Hs Inhibition 5.3 pIC50 18
pIC50 5.3 (IC50 5.56x10-6 M) [18]
Description: In an in vitro enzymatic assay.
serabelisib Hs Inhibition >5.0 pIC50 29
pIC50 >5.0 (IC50 <1x10-5 M) [29]
RapaLink-1 Hs Inhibition - - 31
[31]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 6,37

Key to terms and symbols Click column headers to sort
Target used in screen: MTOR
Ligand Sp. Type Action Affinity Parameter
PP-242 Hs Inhibitor Inhibition 8.5 pKd
PI-103 Hs Inhibitor Inhibition 7.9 pKd
pictilisib Hs Inhibitor Inhibition 6.7 pKd
TG-100-115 Hs Inhibitor Inhibition 6.2 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
erlotinib Hs Inhibitor Inhibition <5.5 pKd
GSK690693 Hs Inhibitor Inhibition <5.5 pKd
masitinib Hs Inhibitor Inhibition <5.5 pKd
A-674563 Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 9...

Key to terms and symbols Click column headers to sort
Target used in screen: mTOR-FKBP12/nd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
sirolimus Hs Inhibitor Inhibition -17.0 4.0
PI-103 Hs Inhibitor Inhibition -12.0 7.0
Akt inhibitor X Hs Inhibitor Inhibition 70.0 98.0
CGP74514A Hs Inhibitor Inhibition 70.0 109.0
AG 9 Hs Inhibitor Inhibition 70.0 101.0
AG 1295 Hs Inhibitor Inhibition 70.0 83.0
Gö 6976 Hs Inhibitor Inhibition 72.0 99.0
CGP53353 Hs Inhibitor Inhibition 73.0 85.0
MEK inhibitor I Hs Inhibitor Inhibition 74.0 95.0
PDGF RTK inhibitor Hs Inhibitor Inhibition 75.0 111.0
Target used in screen: mTOR/nd
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
LY 294002 Hs Inhibitor Inhibition 24.0 27.0
PI 3-Kg inhibitor Hs Inhibitor Inhibition 46.0 51.0
PI-103 Hs Inhibitor Inhibition 49.0 35.0
PKR inhibitor, negative control Hs Inhibitor Inhibition 51.0 64.0
sirolimus Hs Inhibitor Inhibition 57.0 51.0
PKR inhibitor Hs Inhibitor Inhibition 73.0 73.0
isogranulatimide Hs Inhibitor Inhibition 75.0 71.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 76.0 76.0
AG 1024 Hs Inhibitor Inhibition 77.0 86.0
DMBI Hs Inhibitor Inhibition 78.0 101.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Nonsense Human M2327I Activating mutation in the kinase domain of mTOR, which could theoretically confer a growth advantage in transformed cancer cells. 31
Clinically-Relevant Mutations and Pathophysiology Comments
Hyperactivation of mTOR kinase by single amino acid mutations such as M2327I (which has been identified in drug-naive patients) can reduce sensitivity to ATP-competitive mTOR inhibitors in vitro [31].

References

Show »

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. Barda DA, Mader MM. (2013) PI3 kinase/mTOR dual inhibitor. Patent number: US8440829 B2. Assignee: Eli Lilly And Company. Priority date: 14/01/2011. Publication date: 14/05/2013.

3. Cansfield AD, Ladduwahetty T, Sunose M, Ellard K, Lynch R, Newton AL, Lewis A, Bennett G, Zinn N, Thomson DW et al.. (2016) CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model. ACS Med Chem Lett, 7 (8): 768-73. [PMID:27563401]

4. Castro-Falcón G, Seiler GS, Demir Ö, Rathinaswamy MK, Hamelin D, Hoffmann RM, Makowski SL, Letzel AC, Field SJ, Burke JE et al.. (2018) Neolymphostin A Is a Covalent Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitor That Employs an Unusual Electrophilic Vinylogous Ester. J. Med. Chem., [Epub ahead of print]. [PMID:30380865]

5. D'Angelo ND, Kim TS, Andrews K, Booker SK, Caenepeel S, Chen K, D'Amico D, Freeman D, Jiang J, Liu L et al.. (2011) Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors. J. Med. Chem., 54 (6): 1789-811. [PMID:21332118]

6. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

7. Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W et al.. (2012) Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis, 3: e441. [PMID:23222511]

8. Fraser C, Carragher NO, Unciti-Broceta A. (2016) eCF309: a potent, selective and cell-permeable mTOR inhibitor. Med. Chem. Commun., 7 (3): 471-477.

9. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

10. García-Martínez JM, Moran J, Clarke RG, Gray A, Cosulich SC, Chresta CM, Alessi DR. (2009) Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem J, 421 (1): 29-42. [PMID:19402821]

11. Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K. (2012) Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg. Med. Chem. Lett., 22 (21): 6636-41. [PMID:23021994]

12. Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, Cheong A, Ng BK, Amalini C, Madan B et al.. (2013) VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol. Cancer Ther., 12 (2): 151-61. [PMID:23270925]

13. Heffron TP, Ndubaku CO, Salphati L, Alicke B, Cheong J, Drobnick J, Edgar K, Gould SE, Lee LB, Lesnick JD et al.. (2016) Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR. ACS Med Chem Lett, 7 (4): 351-6. [PMID:27096040]

14. 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]

15. Jalota-Badhwar A, Bhatia DR, Boreddy S, Joshi A, Venkatraman M, Desai N, Chaudhari S, Bose J, Kolla LS, Deore V et al.. (2015) P7170: A Novel Molecule with Unique Profile of mTORC1/C2 and Activin Receptor-like Kinase 1 Inhibition Leading to Antitumor and Antiangiogenic Activity. Mol. Cancer Ther., 14 (5): 1095-106. [PMID:25700704]

16. Knight SD, Adams ND, Burgess JL, Chaudhari AM, Darcy MG, Donatelli CA, Luengo JI, Newlander KA, Parrish CA, Ridgers LH et al.. (2010) Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. ACS Med Chem Lett, 1 (1): 39-43. [PMID:24900173]

17. 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]

18. Liu F, Wang J, Yang X, Li B, Wu H, Qi S, Chen C, Liu X, Yu K, Wang W et al.. (2016) Discovery of a Highly Selective STK16 Kinase Inhibitor. ACS Chem. Biol., 11 (6): 1537-43. [PMID:27082499]

19. 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]

20. 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]

21. Liu Q, Wang J, Kang SA, Thoreen CC, Hur W, Ahmed T, Sabatini DM, Gray NS. (2011) Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. J. Med. Chem., 54 (5): 1473-80. [PMID:21322566]

22. 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]

23. Mortensen DS, Perrin-Ninkovic SM, Shevlin G, Zhao J, Packard G, Bahmanyar S, Correa M, Elsner J, Harris R, Lee BG et al.. (2015) Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223. J. Med. Chem., 58 (13): 5323-33. [PMID:26083478]

24. März AM, Fabian AK, Kozany C, Bracher A, Hausch F. (2013) Large FK506-Binding Proteins Shape the Pharmacology of Rapamycin. Mol. Cell. Biol., 33 (7): 1357-67. [PMID:23358420]

25. Ohwada J, Ebiike H, Kawada H, Tsukazaki M, Nakamura M, Miyazaki T, Morikami K, Yoshinari K, Yoshida M, Kondoh O et al.. (2011) Discovery and biological activity of a novel class I PI3K inhibitor, CH5132799. Bioorg. Med. Chem. Lett., 21 (6): 1767-72. [PMID:21316229]

26. Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M. (2013) Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg. Med. Chem. Lett., 23 (5): 1212-6. [PMID:23375793]

27. Rageot D, Bohnacker T, Melone A, Langlois JB, Borsari C, Hillmann P, Sele AM, Beaufils F, Zvelebil M, Hebeisen P et al.. (2018) Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders. J. Med. Chem., 61 (22): 10084-10105. [PMID:30359003]

28. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, Folkes A, Gowan S, De Haven Brandon A, Di Stefano F et al.. (2009) Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol. Cancer Ther., 8 (7): 1725-38. [PMID:19584227]

29. Ren P, Liu Y, Li L, Chan K, Wilson TE, Campbell SF. (2013) Heterocyclic compounds and uses thereof. Patent number: US20130035324 A1. Assignee: Ren P, Liu Y, Li L, Chan K, Wilson TE, Campbell SF.. Priority date: 17/08/2009. Publication date: 07/02/2013.

30. 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]

31. Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E et al.. (2016) Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature, 534 (7606): 272-6. [PMID:27279227]

32. 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]

33. 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]

34. 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]

35. 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]

36. Veverka V, Crabbe T, Bird I, Lennie G, Muskett FW, Taylor RJ, Carr MD. (2008) Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene, 27 (5): 585-95. [PMID:17684489]

37. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

38. Yu K, Toral-Barza L, Shi C, Zhang WG, Lucas J, Shor B, Kim J, Verheijen J, Curran K, Malwitz DJ et al.. (2009) Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res, 69 (15): 6232-40. [PMID:19584280]

How to cite this page

FRAP subfamily: mechanistic target of rapamycin kinase. Last modified on 30/11/2018. Accessed on 20/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2109.