General Information of Drug Combination (ID: DCC3EAT)

Drug Combination Name
Sirolimus Terameprocol
Indication
Disease Entry Status REF
Clear cell renal cell carcinoma Investigative [1]
Component Drugs Sirolimus   DMGW1ID Terameprocol   DMC3P45
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: A498
Zero Interaction Potency (ZIP) Score: 0.19
Bliss Independence Score: 1.84
Loewe Additivity Score: 2.12
LHighest Single Agent (HSA) Score: 1.72

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sirolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Brainstem neoplasm N.A. Approved [2]
Graft-versus-host disease 4B24 Approved [2]
Intracranial meningioma N.A. Approved [2]
Lung cancer 2C25.0 Approved [2]
Lung lymphangioleiomyomatosis N.A. Approved [2]
Lymphangioleiomyomatosis CB07 Approved [3]
Mucosal melanoma N.A. Approved [2]
Multiple myeloma 2A83 Approved [4]
Multiple sclerosis 8A40 Approved [2]
Non-small-cell lung cancer 2C25.Y Approved [2]
Organ transplant rejection NE84 Approved [5]
Plasma cell myeloma 2A83.1 Approved [2]
Prostate cancer 2C82.0 Approved [2]
Salivary gland squamous cell carcinoma N.A. Approved [2]
Uveitis 9A96.Z Phase 3 [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [7]
Dutch elm disease 8D64 Phase 1/2 [5]
Castration-resistant prostate carcinoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
Pancreatic acinar cell carcinoma N.A. Investigative [2]
Polycystic kidney disease GB8Y Investigative [2]
Rheumatoid arthritis FA20 Investigative [2]
Sirolimus Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [9]
PI3K/AKT/mTOR pathway (PAm pathway) TTGQUFK NOUNIPROTAC Inhibitor [10]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [11]
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Sirolimus Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [13]
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Sirolimus Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [15]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [15]
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Sirolimus Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Increases ADR [16]
Calcineurin subunit B type 1 (PPP3R1) OTGQNFJQ CANB1_HUMAN Increases ADR [16]
Nuclear receptor ROR-gamma (RORC) OTUBFRPC RORG_HUMAN Increases ADR [16]
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Indication(s) of Terameprocol
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [8]
Terameprocol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Transcription factor Sp1 (SP1) TTZEP6S SP1_HUMAN Modulator [8]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Chronic myelogenous leukemia DCSPGGO K-562 Investigative [1]
Glioma DCWY3GX SF-539 Investigative [1]
Glioma DCKZ4GY SF-295 Investigative [1]
Carcinoma DC03ATX MCF7 Investigative [17]
Colon carcinoma DCH6Y5W KM12 Investigative [17]
Invasive ductal carcinoma DCBLKPP T-47D Investigative [17]
Adenocarcinoma DC9CTJ7 HCT116 Investigative [18]
Amelanotic melanoma DCUOZAI M14 Investigative [18]
Prostate carcinoma DCICKFD PC-3 Investigative [18]
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⏷ Show the Full List of 9 DrugCom(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Sirolimus FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 201578.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 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).
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 ClinicalTrials.gov (NCT04341675) Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia. U.S. National Institutes of Health.
8 Terameprocol, a novel site-specific transcription inhibitor with anticancer activity. IDrugs. 2008 Mar;11(3):204-14.
9 Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
10 The genomic landscape of nasopharyngeal carcinoma.Nat Genet. 2014 Aug;46(8):866-71.
11 Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14.
12 Pharmacogenetics of tacrolimus and sirolimus in renal transplant patients: from retrospective analyses to prospective studies. Transplant Proc. 2007 Sep;39(7):2142-4.
13 Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2010 Jun;87(6):663-7.
14 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
15 Drug Interactions Flockhart Table
16 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
17 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
18 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.