General Information of Drug Combination (ID: DC5LC1P)

Drug Combination Name
Everolimus MK-4827
Indication
Disease Entry Status REF
Breast Cancer Phase 1 [1]
Component Drugs Everolimus   DM8X2EH MK-4827   DMLYGH4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Advanced/metastatic breast cancer 2C60 Approved [3]
Brainstem neoplasm N.A. Approved [2]
Breast carcinoma N.A. Approved [2]
Graft-versus-host disease 4B24 Approved [2]
Intracranial meningioma N.A. Approved [2]
Leukemia N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Mucosal melanoma N.A. Approved [2]
Multiple sclerosis 8A40 Approved [2]
Plasma cell myeloma 2A83.1 Approved [2]
Prostate cancer 2C82.0 Approved [2]
Renal cell carcinoma 2C90 Approved [4]
Salivary gland squamous cell carcinoma N.A. Approved [2]
Tuberous sclerosis LD2D.2 Approved [2]
Kidney cancer 2C90.0 Phase 3 [4]
Castration-resistant prostate carcinoma N.A. Investigative [2]
Colon cancer 2B90.Z Investigative [2]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Neuroblastoma 2D11.2 Investigative [2]
Pancreatic acinar cell carcinoma N.A. Investigative [2]
Polycystic kidney disease GB8Y Investigative [2]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [8]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [5]
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Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Indication(s) of MK-4827
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 3 [6]
Breast cancer 2C60-2C65 Phase 2 [7]
Ewing sarcoma 2B52 Phase 1 [7]
MK-4827 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Poly [ADP-ribose] polymerase (PARP) TTEBCY8 NOUNIPROTAC Modulator [11]
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MK-4827 Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [12]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [13]
Beta-glucuronidase (GUSB) DEP54UE BGLR_HUMAN Metabolism [13]
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MK-4827 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [14]
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References

1 ClinicalTrials.gov (NCT03154281) Evaluation of the Safety and Tolerability of Niraparib With Everolimus in Advanced Gynecologic Malignancies and Breast
2 Everolimus FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 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).
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 ClinicalTrials.gov (NCT03602859) A Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care (SOC) Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST). U.S. National Institutes of Health.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 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.
9 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.
10 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
11 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
12 Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009 Nov 26;52(22):7170-85.
13 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
14 Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods. 2022 Feb;32(2):87-96. doi: 10.1080/15376516.2021.1968985. Epub 2021 Aug 26.