Details of the Drug Combination

General Information of Drug Combination (ID: DCV4SPO)

Drug Combination Name
Ruxolitinib 10-hydroxycamptothecin
Indication
Disease Entry Status REF
Anaplastic large cell lymphoma Investigative [1]
Component Drugs Ruxolitinib   DM7Q98D 10-hydroxycamptothecin   DM9WLN4
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SR
Zero Interaction Potency (ZIP) Score: 3.7
Bliss Independence Score: 2.96
Loewe Additivity Score: 0.21
LHighest Single Agent (HSA) Score: 3.27

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ruxolitinib
Disease Entry ICD 11 Status REF
Essential thrombocythemia 3B63.1Z Approved [2]
High-risk myelofibrosis 2A20.2 Approved [3]
Myelofibrosis 2A22 Approved [4]
Myeloproliferative neoplasm 2A20 Approved [5]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
Pancreatic cancer 2C10 Phase 3 [3]
Atopic dermatitis EA80 Phase 1/2 [7]
Vitiligo ED63.0 Phase 1/2 [7]
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 [9]
Janus kinase 1 (JAK-1) TT6DM01 JAK1_HUMAN Modulator [9]
Urokinase plasminogen activator surface receptor (PLAUR) TTPRL03 UPAR_HUMAN Inhibitor [10]
HUMAN janus kinase 1 (JAK-1) TTWKB01 JAK1_HUMAN Inhibitor [11]
HUMAN janus kinase 2 (JAK-2) TT0F5HE JAK2_HUMAN Inhibitor [11]
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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 [12]
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Indication(s) of 10-hydroxycamptothecin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [8]
10-hydroxycamptothecin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase I (TOP1) TTGTQHC TOP1_HUMAN Inhibitor [8]
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10-hydroxycamptothecin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [13]
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10-hydroxycamptothecin Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Response To Substance [14]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Affects Response To Substance [15]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [14]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Chronic myelogenous leukemia DCXZK8U K-562 Investigative [1]
Adenocarcinoma DCOAA3J SW-620 Investigative [16]
Lung adenocarcinoma DCO2Z54 MDA-MB-231 Investigative [16]
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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 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: 5688).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Ruxolitinib FDA Label
6 Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8 Upregulation of p21WAF1/CIP1 in human breast cancer cell lines MCF-7 and MDA-MB-468 undergoing apoptosis induced by natural product anticancer drugs 10-hydroxycamptothecin and camptothecin through p53-dependent and independent pathways. Int J Oncol. 1998 Apr;12(4):793-804.
9 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
10 Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
11 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.
12 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.
13 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
14 siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma cells to chemotherapeutic drugs. Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):450-6. doi: 10.1111/j.1440-1681.2007.04593.x.
15 Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11636-41. doi: 10.1073/pnas.1934692100. Epub 2003 Sep 16.
16 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.