Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMQ63J2)

• Drug Name: EM-101 Drug Info
• Synonyms: EM-100 series; LY-3; LY-303511; MTOR pathway inhibitors (cancer), Emiliem; MTOR pathway inhibitors (cancer), NIH

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 3971
  ChEBI ID: CHEBI:92399
  CAS Number: CAS 154447-38-8
  TTD Drug ID: DMQ63J2

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase mTOR (mTOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[4]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[5]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[6]
Everolimus	DM8X2EH	Advanced cancer	2A00-2F9Z	Approved	[7]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[2]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[9]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[11]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[2]

Drug(s) Affected By MAP kinase-activated protein kinase 2 (MAPKAPK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[15]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Sorbitol	DMAN0DE	Constipation	DD91.1	Approved	[12]
Bortezomib	DMNO38U	Leukemia		Approved	[17]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[18]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[19]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[20]

Drug(s) Affected By Tumor necrosis factor ligand superfamily member 10 (TNFSF10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bepridil	DM0RKS4	Chronic/stable angina	BA40.1	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
Selenium	DM25CGV	N. A.	N. A.	Approved	[23]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[24]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[25]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
MAP kinase-activated protein kinase 2 (MAPKAPK2)	OT460SBO	MAPK2_HUMAN	Post-Translational Modifications	[3]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] 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: 6005).
• [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. (Target id: 2109).
• [3] Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27. Cell Death Dis. 2013 Oct 31;4(10):e890. doi: 10.1038/cddis.2013.413.
• [4] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [5] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 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.
• [8] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [9] 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.
• [10] Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways. J Biol Chem. 1998 Apr 17;273(16):9373-7. doi: 10.1074/jbc.273.16.9373.
• [13] Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology. 2009 Feb 27;256(3):183-90. doi: 10.1016/j.tox.2008.11.016. Epub 2008 Nov 28.
• [14] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [15] Pregnane X receptor PXR activates the GADD45beta gene, eliciting the p38 MAPK signal and cell migration. J Biol Chem. 2011 Feb 4;286(5):3570-8. doi: 10.1074/jbc.M110.179812. Epub 2010 Dec 2.
• [16] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [17] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [20] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [21] Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation. Neuro Oncol. 2011 Mar;13(3):267-79. doi: 10.1093/neuonc/noq195. Epub 2011 Feb 3.
• [22] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [23] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [24] Two distinct phases of virus-induced nuclear factor kappa B regulation enhance tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in virus-infected cells. J Biol Chem. 2003 May 16;278(20):18092-100. doi: 10.1074/jbc.M300265200. Epub 2003 Mar 13.
• [25] TNF-related apoptosis-inducing ligand cooperates with NSAIDs via activated Wnt signalling in (pre)malignant colon cells. J Pathol. 2011 Feb;223(3):378-89. doi: 10.1002/path.2797. Epub 2010 Oct 29.
• [26] Peripheral blood expression of nuclear factor-kappab-regulated genes is associated with rheumatoid arthritis disease activity and responds differentially to anti-tumor necrosis factor-alpha versus methotrexate. J Rheumatol. 2007 Sep;34(9):1817-22. Epub 2007 Aug 1.
• [27] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [28] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [29] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [30] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.