Target General Infomation
Target ID
T75243 (Former ID: TTDS00265)
Target Name
Serine/threonine-protein kinase mTOR (mTOR)
Synonyms
Target of rapamycin; TOR kinase; Rapamycin target protein 1; Rapamycin target protein; Rapamycin and FKBP12 target 1; RAPT1; RAFT1; Mechanistic target of rapamycin; Mammalian target of rapamycin; FRAP2; FRAP1; FRAP; FKBP12-rapamycin complex-associated protein; FKBP-rapamycin associated protein; FK506-binding protein 12-rapamycin complex-associated protein 1
Gene Name
MTOR
Target Type
Successful target
[1]
Disease [+] 6 Target-related Diseases +
1 Arteries/arterioles disorder [ICD-11: BD52]
2 Chronic myelomonocytic leukaemia [ICD-11: 2A40]
3 Multiple myeloma [ICD-11: 2A83]
4 Renal cell carcinoma [ICD-11: 2C90]
5 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
6 Transplant rejection [ICD-11: NE84]
Function
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms. Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks. Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
BioChemical Class
Kinase
UniProt ID
MTOR_HUMAN
EC Number
EC 2.7.11.1
Sequence
MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEES
TRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDP
VVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVP
TFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEE
AEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYC
KDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESR
CCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHV
LSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDA
TVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLL
KMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLT
QFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLL
VVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSS
MNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALI
LKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVA
LWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHK
VNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFR
DQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLV
SFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLR
VFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVD
RLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLV
RHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHV
STINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNA
AFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGI
VLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHF
GELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEK
WTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLA
QQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWW
ERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVD
PSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHK
QELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEA
VLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSP
TPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVN
EALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVAS
KSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFG
ERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQA
WDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSL
QVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNL
SIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTL
MQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRH
PSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITC
HTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDG
VELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLD
VPTQVELLIKQATSHENLCQCYIGWCPFW
Drugs and Modes of Action
Approved Drug(s) [+] 7 Approved Drugs +
1 Everolimus Drug Info Approved Renal cell carcinoma [2], [3]
2 Novolimus Drug Info Approved Artery stenosis [4], [5]
3 PF-04449913 Drug Info Approved Chronic myelomonocytic leukaemia [6]
4 Rapamycin Drug Info Approved Multiple myeloma [7], [8]
5 Sirolimus Drug Info Approved Organ transplant rejection [9], [10]
6 Temsirolimus Drug Info Approved Renal cell carcinoma [1], [11]
7 Zotarolimus Drug Info Approved Solid tumour/cancer [7], [12], [13]
Clinical Trial Drug(s) [+] 26 Clinical Trial Drugs +
1 Ridaforolimus Drug Info Phase 3 Sarcoma [14], [15]
2 ABI-009 Drug Info Phase 2 Solid tumour/cancer [16]
3 AZD2014 Drug Info Phase 2 Solid tumour/cancer [17], [18]
4 BEZ235 Drug Info Phase 2 Solid tumour/cancer [19], [20]
5 GDC-0980/RG7422 Drug Info Phase 2 Non-hodgkin lymphoma [21]
6 INK128 Drug Info Phase 2 Breast cancer [22]
7 LY3023414 Drug Info Phase 2 Solid tumour/cancer [23]
8 MM-141 Drug Info Phase 2 Solid tumour/cancer [24]
9 OSI-027 Drug Info Phase 2 Renal cell carcinoma [25]
10 PF-04691502 Drug Info Phase 2 Endometrial cancer [26], [27]
11 PF-05212384 Drug Info Phase 2 Solid tumour/cancer [22], [28], [29]
12 Salirasib Drug Info Phase 2 Lung cancer [30], [31]
13 SAR245409 Drug Info Phase 2 Solid tumour/cancer [32]
14 SF1126 Drug Info Phase 2 Head and neck cancer [22]
15 BGT226 Drug Info Phase 1/2 Solid tumour/cancer [33], [34]
16 CC-223 Drug Info Phase 1/2 Solid tumour/cancer [35]
17 ME-344 Drug Info Phase 1/2 Breast cancer [22]
18 BI 860585 Drug Info Phase 1 Solid tumour/cancer [36]
19 DS-3078 Drug Info Phase 1 Lymphoma [37]
20 DS-7423 Drug Info Phase 1 Solid tumour/cancer [38]
21 GDC-0349 Drug Info Phase 1 Non-hodgkin lymphoma [39]
22 LAM-001 Drug Info Phase 1 Lymphangioleiomyomatosis [40]
23 PQR309 Drug Info Phase 1 Pain [41]
24 PWT-33597 Drug Info Phase 1 Solid tumour/cancer [42]
25 VE-822 Drug Info Phase 1 Solid tumour/cancer [22]
26 VS-5584 Drug Info Phase 1 Solid tumour/cancer [43], [44]
Discontinued Drug(s) [+] 3 Discontinued Drugs +
1 AZD8055 Drug Info Discontinued in Phase 1/2 Solid tumour/cancer [45], [46]
2 TAFA-93 Drug Info Discontinued in Phase 1 Transplant rejection [47]
3 SCR-44001 Drug Info Terminated Solid tumour/cancer [48]
Mode of Action [+] 2 Modes of Action +
Inhibitor [+] 61 Inhibitor drugs +
1 Everolimus Drug Info [49]
2 Novolimus Drug Info [50]
3 PF-04449913 Drug Info [51]
4 Rapamycin Drug Info [52]
5 Sirolimus Drug Info [53]
6 Temsirolimus Drug Info [1], [7]
7 Ridaforolimus Drug Info [55], [56]
8 ABI-009 Drug Info [22]
9 AZD2014 Drug Info [57]
10 INK128 Drug Info [60]
11 MM-141 Drug Info [22]
12 OSI-027 Drug Info [62]
13 SAR245409 Drug Info [50], [64]
14 SF1126 Drug Info [22]
15 ME-344 Drug Info [66]
16 BI 860585 Drug Info [67]
17 GDC-0349 Drug Info [70]
18 LAM-001 Drug Info [40]
19 PQR309 Drug Info [50]
20 VE-822 Drug Info [72]
21 PMID25726713-Compound-47 Drug Info [73]
22 PMID25726713-Compound-48 Drug Info [73]
23 PMID25726713-Compound-49 Drug Info [73]
24 PMID25726713-Compound-50 Drug Info [73]
25 PMID25726713-Compound-51 Drug Info [73]
26 AZD8055 Drug Info [74]
27 TAFA-93 Drug Info [75]
28 SCR-44001 Drug Info [76]
29 (4-(6-morpholino-9H-purin-2-yl)phenyl)methanol Drug Info [77]
30 2-(2-Methyl-morpholin-4-yl)-benzo[h]chromen-4-one Drug Info [78]
31 2-(6-morpholino-9H-purin-2-yl)phenol Drug Info [77]
32 2-chloro-N-(6-cyanopyridin-3-yl)propanamide Drug Info [79]
33 2-Morpholin-4-yl-pyrimido[2,1-a]isoquinolin-4-one Drug Info [78]
34 3-(6-morpholino-9H-purin-2-yl)phenol Drug Info [77]
35 4-(2-(1H-indol-6-yl)-9H-purin-6-yl)morpholine Drug Info [77]
36 4-(2-(thiophen-2-yl)-9H-purin-6-yl)morpholine Drug Info [77]
37 4-(2-(thiophen-3-yl)-9H-purin-6-yl)morpholine Drug Info [77]
38 4-(6-morpholino-9H-purin-2-yl)phenol Drug Info [77]
39 AP-21967 Drug Info [80]
40 AR-mTOR-26 Drug Info [50]
41 C-16-(S)-3-methylindolerapamycin Drug Info [80]
42 CU-906 Drug Info [50]
43 Dual PI3K-alpha/mTOR inhibitors Drug Info [50]
44 Dual PI3K/mTOR inhibitors Drug Info [50]
45 EC-0565 Drug Info [50]
46 EM-101 Drug Info [50]
47 Ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxylate Drug Info [78]
48 HM-5016699 Drug Info [50]
49 Macrolide derivative Drug Info [81]
50 MTOR inhibitors (cancer), Amgen Drug Info [50]
51 OXA-01 Drug Info [50]
52 P-2281 Drug Info [50]
53 P-6915 Drug Info [50]
54 PF-03772304 Drug Info [82]
55 PF-05094037 Drug Info [50]
56 PP-242 Drug Info [83]
57 PP121 Drug Info [83]
58 Rapamycin complexed with immunophilin FKBP12 Drug Info [84]
59 SB-2280 Drug Info [50]
60 torin 1 Drug Info [85]
61 X-387 Drug Info [50]
Modulator [+] 15 Modulator drugs +
1 Zotarolimus Drug Info [54]
2 BEZ235 Drug Info [58]
3 GDC-0980/RG7422 Drug Info [50], [59]
4 LY3023414 Drug Info [61]
5 PF-04691502 Drug Info [63]
6 PF-05212384 Drug Info [29]
7 Salirasib Drug Info [50]
8 BGT226 Drug Info [34]
9 CC-223 Drug Info [65]
10 DS-3078 Drug Info [68]
11 DS-7423 Drug Info [69]
12 PWT-33597 Drug Info [71]
13 VS-5584 Drug Info [44], [50]
14 EC-0845 Drug Info [50]
15 SX-MTR1 Drug Info [50]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Drug Resistance
 Mutation (DRM)
Target Affiliated Biological Pathways
KEGG Pathway [+] 17 KEGG Pathways +
1 ErbB signaling pathway
2 HIF-1 signaling pathway
3 mTOR signaling pathway
4 PI3K-Akt signaling pathway
5 AMPK signaling pathway
6 Insulin signaling pathway
7 Thyroid hormone signaling pathway
8 Adipocytokine signaling pathway
9 Type II diabetes mellitus
10 Pathways in cancer
11 Proteoglycans in cancer
12 MicroRNAs in cancer
13 Glioma
14 Prostate cancer
15 Acute myeloid leukemia
16 Central carbon metabolism in cancer
17 Choline metabolism in cancer
Panther Pathway [+] 2 Panther Pathways +
1 Hypoxia response via HIF activation
2 Interleukin signaling pathway
Pathwhiz Pathway [+] 1 Pathwhiz Pathways +
1 Leucine Stimulation on Insulin Signaling
PID Pathway [+] 15 PID Pathways +
1 IL4-mediated signaling events
2 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
3 IL12-mediated signaling events
4 CDC42 signaling events
5 LKB1 signaling events
6 Regulation of Telomerase
7 mTOR signaling pathway
8 CXCR4-mediated signaling events
9 EGFR-dependent Endothelin signaling events
10 IL2 signaling events mediated by PI3K
11 IFN-gamma pathway
12 ErbB1 downstream signaling
13 ErbB2/ErbB3 signaling events
14 CXCR3-mediated signaling events
15 Class I PI3K signaling events mediated by Akt
Reactome [+] 8 Reactome Pathways +
1 PIP3 activates AKT signaling
2 Macroautophagy
3 mTORC1-mediated signalling
4 HSF1-dependent transactivation
5 CD28 dependent PI3K/Akt signaling
6 VEGFR2 mediated vascular permeability
7 TP53 Regulates Metabolic Genes
8 Constitutive Signaling by AKT1 E17K in Cancer
WikiPathways [+] 29 WikiPathways +
1 ErbB Signaling Pathway
2 Senescence and Autophagy in Cancer
3 Interferon type I signaling pathways
4 Insulin Signaling
5 EGF/EGFR Signaling Pathway
6 Wnt Signaling Pathway Netpath
7 Extracellular vesicle-mediated signaling in recipient cells
8 Cardiac Hypertrophic Response
9 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
10 PIP3 activates AKT signaling
11 Polycystic Kidney Disease Pathway
12 Alpha 6 Beta 4 signaling pathway
13 BDNF signaling pathway
14 Oncostatin M Signaling Pathway
15 Prostate Cancer
16 TSLP Signaling Pathway
17 FSH signaling pathway
18 Leptin signaling pathway
19 TSH signaling pathway
20 RANKL/RANK Signaling Pathway
21 SREBF and miR33 in cholesterol and lipid homeostasis
22 Integrated Breast Cancer Pathway
23 SREBP signalling
24 Signaling by Insulin receptor
25 Costimulation by the CD28 family
26 Type II diabetes mellitus
27 MicroRNAs in cardiomyocyte hypertrophy
28 TOR Signaling
29 AMPK Signaling
Target-Related Models and Studies
Target Validation
References
REF 1 Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
REF 2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5889).
REF 3 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
REF 4 Clinical pipeline report, company report or official report of Elixir.
REF 5 ClinicalTrials.gov (NCT02009956) EXCELLA Post-Approval Study. U.S. National Institutes of Health.
REF 6 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
REF 7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 8 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002452)
REF 9 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6031).
REF 10 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
REF 11 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5892).
REF 12 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7974).
REF 13 ClinicalTrials.gov (NCT00589927) Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent. U.S. National Institutes of Health.
REF 14 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7884).
REF 15 Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. J Clin Oncol. 2012 Jan 1;30(1):78-84.
REF 16 ClinicalTrials.gov (NCT02494570) A Phase 2 Study of ABI-009 in Patients With Advanced Malignant PEComa.
REF 17 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7699).
REF 18 ClinicalTrials.gov (NCT01793636) A Study Comparing AZD2014 vs Everolimus in Patients With Metastatic Renal Cancer. U.S. National Institutes of Health.
REF 19 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7950).
REF 20 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026094)
REF 21 Clinical pipeline report, company report or official report of Roche.
REF 22 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 23 ClinicalTrials.gov (NCT02549989) Study of LY3023414 for the Treatment of Recurrent.
REF 24 ClinicalTrials.gov (NCT02399137) A Phase 2 Study of MM-141 Plus Nab-paclitaxel and Gemcitabine in Front-line Metastatic Pancreatic Cancer. U.S. National Institutes of Health.
REF 25 Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin. Mol Cancer Ther. 2011 Aug;10(8):1394-406.
REF 26 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7936).
REF 27 ClinicalTrials.gov (NCT01430585) Pre-Operative Study of PF-4691502 With Letrozole Compared To Letrozole Alone In Patients With Early Breast Cancer. U.S. National Institutes of Health.
REF 28 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7940).
REF 29 First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.
REF 30 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6281).
REF 31 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026972)
REF 32 ClinicalTrials.gov (NCT01936363) Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer. U.S. National Institutes of Health.
REF 33 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7951).
REF 34 Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma. Anticancer Drugs. 2012 Jan;23(1):131-8.
REF 35 ClinicalTrials.gov (NCT01177397) Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma. U.S. NationalInstitutes of Health.
REF 36 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038828)
REF 37 ClinicalTrials.gov (NCT01588678) A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas. U.S. National Institutes of Health.
REF 38 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034336)
REF 39 ClinicalTrials.gov (NCT01356173) Evaluating the Safety and Tolerability of GDC-0349 in Patients With Locally Advanced or Metastatic Solid Tumors or Non Hodgkin's Lymphoma. U.S. National Institutes ofHealth.
REF 40 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 41 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8383).
REF 42 ClinicalTrials.gov (NCT01407380) Study of PWT33597 Mesylate in Subjects With Advanced Malignancies. U.S. National Institutes of Health.
REF 43 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8382).
REF 44 VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61.
REF 45 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7714).
REF 46 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028731)
REF 47 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018935)
REF 48 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022134)
REF 49 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
REF 50 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2109).
REF 51 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 52 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
REF 53 Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
REF 54 Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
REF 55 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
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