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

General Information of Drug (ID: DM8X2EH)

• Drug Name: Everolimus Drug Info
• Synonyms: Afinitor; Afinitor (TN); CERTICAN(R); Certican; Certican (TN); Everolimus (JAN/USAN/INN); Everolimus [USAN]; MTOR kinase inhibitors; NVP-RAD-001; RAD 001; RAD-001; RAD-001C; RAD001; RAD001, SDZ-RAD, Certican, Zortress, Afinitor, Everolimus; SDZ-RAD; Zortress

Indication

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[1]
Advanced/metastatic breast cancer	2C60	Approved	[2]
Brainstem neoplasm		Approved	[1]
Breast carcinoma		Approved	[1]
Graft-versus-host disease	4B24	Approved	[1]
Intracranial meningioma		Approved	[1]
Leukemia		Approved	[1]
Lung cancer	2C25.0	Approved	[1]
Mucosal melanoma		Approved	[1]
Multiple sclerosis	8A40	Approved	[1]
Plasma cell myeloma	2A83.1	Approved	[1]
Prostate cancer	2C82.0	Approved	[1]
Renal cell carcinoma	2C90	Approved	[3]
Salivary gland squamous cell carcinoma		Approved	[1]
Tuberous sclerosis	LD2D.2	Approved	[1]
Kidney cancer	2C90.0	Phase 3	[3]
Castration-resistant prostate carcinoma		Investigative	[1]
Colon cancer	2B90.Z	Investigative	[1]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[4]
Neuroblastoma	2D11.2	Investigative	[1]
Pancreatic acinar cell carcinoma		Investigative	[1]
Polycystic kidney disease	GB8Y	Investigative	[1]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[4]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 6442177
  ChEBI ID: CHEBI:68478
  CAS Number: CAS 159351-69-6
  TTD Drug ID: DM8X2EH
  VARIDT Drug ID: DR00224
  INTEDE Drug ID: DR0674
  ACDINA Drug ID: D00260

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	[8]
Temsirolimus	DMS104F	Renal cell carcinoma	2C90	Approved	[9]
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[10]
Novolimus	DM6ZPLQ	Artery stenosis	BD52	Approved	[11]
Zotarolimus	DMRMCXW	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Ridaforolimus	DMLHEU7	Sarcoma	2A60-2C35	Phase 3	[13]
AZD2014	DMOEARH	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
MM-141	DM2RJ4D	Pancreatic cancer	2C10	Phase 2	[15]
PQR309	DMMCYZ8	Squamous head and neck cell carcinom	2D60.0	Phase 2	[11]
Salirasib	DMRSU4X	Lung cancer	2C25.0	Phase 2	[11]

Drug(s) Targeting HUMAN mammalian target of rapamycin (mTOR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sirolimus	DMGW1ID	Advanced cancer	2A00-2F9Z	Approved	[16]
Rapamycin	DM8GRJK	Lymphangioleiomyomatosis	CB07	Investigative	[4]
Sapanisertib	DMYZFNH	Breast cancer	2C60-2C65	Investigative	[17]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[18]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[20]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[21]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[20]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[20]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[25]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[26]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[27]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[28]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[29]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[31]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[32]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[33]

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	[5]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[7]

References

• [1] Everolimus FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 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).
• [4] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [5] 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.
• [6] Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
• [7] The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
• [8] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [9] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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. (Target id: 2109).
• [12] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [13] 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.
• [14] 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.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14.
• [17] Prevent COVID-19 Severity by Repurposing mTOR Inhibitors. 2 April 2020
• [18] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [19] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [20] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [21] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [22] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [23] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [24] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [25] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [26] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [27] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [28] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [29] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [30] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [31] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [32] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [33] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.