General Information of Drug Combination (ID: DCV3UD5)

Drug Combination Name
Ospemifene Ruxolitinib
Indication
Disease Entry Status REF
Hodgkin lymphoma Investigative [1]
Component Drugs Ospemifene   DMC4GEI Ruxolitinib   DM7Q98D
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: L-1236
Zero Interaction Potency (ZIP) Score: 6.777
Bliss Independence Score: 11.014
Loewe Additivity Score: 5.293
LHighest Single Agent (HSA) Score: 6.982

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ospemifene
Disease Entry ICD 11 Status REF
Dyspareunia GA12 Approved [2]
Postmenopausal vaginal atrophy GA30.2 Phase 3 [2]
Ospemifene Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Modulator [9]
------------------------------------------------------------------------------------
Ospemifene Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [10]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Ospemifene Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [11]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [11]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Decreases Expression [11]
------------------------------------------------------------------------------------
Indication(s) of Ruxolitinib
Disease Entry ICD 11 Status REF
Essential thrombocythemia 3B63.1Z Approved [3]
High-risk myelofibrosis 2A20.2 Approved [4]
Myelofibrosis 2A22 Approved [5]
Myeloproliferative neoplasm 2A20 Approved [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [7]
Pancreatic cancer 2C10 Phase 3 [4]
Atopic dermatitis EA80 Phase 1/2 [8]
Vitiligo ED63.0 Phase 1/2 [8]
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 [12]
Janus kinase 1 (JAK-1) TT6DM01 JAK1_HUMAN Modulator [12]
Urokinase plasminogen activator surface receptor (PLAUR) TTPRL03 UPAR_HUMAN Inhibitor [13]
HUMAN janus kinase 1 (JAK-1) TTWKB01 JAK1_HUMAN Inhibitor [14]
HUMAN janus kinase 2 (JAK-2) TT0F5HE JAK2_HUMAN Inhibitor [14]
------------------------------------------------------------------------------------
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 [15]
------------------------------------------------------------------------------------

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 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: 7349).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 5688).
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Ruxolitinib FDA Label
7 Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 Clinical pipeline report, company report or official report of Shionogi (2011).
10 Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61.
11 Effects of ospemifene, a novel selective estrogen-receptor modulator, on human breast tissue ex vivo. Menopause. 2016 Jul;23(7):719-30. doi: 10.1097/GME.0000000000000624.
12 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
13 Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
14 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.
15 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.