General Information of Drug Combination (ID: DCPMM2G)

Drug Combination Name
GSK525762 Ruxolitinib
Indication
Disease Entry Status REF
Hodgkin lymphoma Investigative [1]
Component Drugs GSK525762   DMPAWBN Ruxolitinib   DM7Q98D
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: L-1236
Zero Interaction Potency (ZIP) Score: 7.23
Bliss Independence Score: 4.8
Loewe Additivity Score: 1.55
LHighest Single Agent (HSA) Score: 4.55

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GSK525762
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
GSK525762 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bromodomain-containing protein 4 (BRD4) TTRA6BO BRD4_HUMAN Modulator [11]
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [2]
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GSK525762 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [12]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [13]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [13]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [13]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [14]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [14]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [10]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [10]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [13]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [10]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Ruxolitinib
Disease Entry ICD 11 Status REF
Essential thrombocythemia 3B63.1Z Approved [4]
High-risk myelofibrosis 2A20.2 Approved [5]
Myelofibrosis 2A22 Approved [6]
Myeloproliferative neoplasm 2A20 Approved [7]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [8]
Pancreatic cancer 2C10 Phase 3 [5]
Atopic dermatitis EA80 Phase 1/2 [9]
Vitiligo ED63.0 Phase 1/2 [9]
Ruxolitinib Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Modulator [15]
Janus kinase 1 (JAK-1) TT6DM01 JAK1_HUMAN Modulator [15]
Urokinase plasminogen activator surface receptor (PLAUR) TTPRL03 UPAR_HUMAN Inhibitor [16]
HUMAN janus kinase 1 (JAK-1) TTWKB01 JAK1_HUMAN Inhibitor [17]
HUMAN janus kinase 2 (JAK-2) TT0F5HE JAK2_HUMAN Inhibitor [17]
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Ruxolitinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Mitogen-activated protein kinase 14 (MAPK14) OT5TCO3O MK14_HUMAN Increases ADR [18]
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References

1 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.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 7033).
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 5688).
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Ruxolitinib FDA Label
8 Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
11 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
12 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
13 An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
14 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
15 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
16 Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
17 The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
18 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.