General Information of Drug Combination (ID: DCJO842)

Drug Combination Name
Sirolimus Valrubicin
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs Sirolimus   DMGW1ID Valrubicin   DMOYJFK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: SNB-75
Zero Interaction Potency (ZIP) Score: 2.6
Bliss Independence Score: 2.33
Loewe Additivity Score: 3.22
LHighest Single Agent (HSA) Score: 3.44

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 [10]
PI3K/AKT/mTOR pathway (PAm pathway) TTGQUFK NOUNIPROTAC Inhibitor [11]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [12]
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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 [13]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [14]
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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 [15]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [16]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [16]
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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 [17]
Calcineurin subunit B type 1 (PPP3R1) OTGQNFJQ CANB1_HUMAN Increases ADR [17]
Nuclear receptor ROR-gamma (RORC) OTUBFRPC RORG_HUMAN Increases ADR [17]
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Indication(s) of Valrubicin
Disease Entry ICD 11 Status REF
Bladder cancer 2C94 Approved [8]
In situ carcinoma N.A. Approved [9]
Urinary bladder cancer N.A. Approved [9]
Psoriasis vulgaris EA90 Phase 2 [4]
Valrubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Inhibitor [18]
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Valrubicin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [19]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Clear cell renal cell carcinoma DCCVTMP 786-0 Investigative [1]
Carcinoma DCG520H RXF 393 Investigative [20]
Invasive ductal carcinoma DCCR4QT BT-549 Investigative [20]
Adenocarcinoma DCE7YV4 OVCAR3 Investigative [21]
High grade ovarian serous adenocarcinoma DCBP3RP OVCAR-5 Investigative [21]
Lung adenocarcinoma DCNMBPY HOP-62 Investigative [21]
Lung adenocarcinoma DCXT7RI EKVX Investigative [21]
Malignant melanoma DC0ODXH UACC62 Investigative [21]
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⏷ Show the Full List of 8 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 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
9 Valrubicin FDA Label
10 Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
11 The genomic landscape of nasopharyngeal carcinoma.Nat Genet. 2014 Aug;46(8):866-71.
12 Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14.
13 Pharmacogenetics of tacrolimus and sirolimus in renal transplant patients: from retrospective analyses to prospective studies. Transplant Proc. 2007 Sep;39(7):2142-4.
14 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.
15 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
16 Drug Interactions Flockhart Table
17 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.
18 Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
19 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
20 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.
21 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.