Details of the Drug Combination

General Information of Drug Combination (ID: DCI8OQR)

Drug Combination Name
PHA-739358 Ramelteon
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PHA-739358   DMGYBZI Ramelteon   DM7IW9J
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 3.19
Bliss Independence Score: 3.19
Loewe Additivity Score: 17.18
LHighest Single Agent (HSA) Score: 17.19

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PHA-739358
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Phase 2 [2]
PHA-739358 Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [4]
Aurora B messenger RNA (AURKB mRNA) TT9RTBL AURKB_HUMAN Inhibitor [5]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [4]
Aurora kinase C (AURKC) TTLYXIT AURKC_HUMAN Inhibitor [5]
------------------------------------------------------------------------------------
PHA-739358 Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Decreases Response To Substance [6]
------------------------------------------------------------------------------------
Indication(s) of Ramelteon
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [3]
Circadian rhythm sleep disorder 7A60-7A65 Terminated [3]
Ramelteon Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Melatonin receptor type 1B (MTNR1B) TT32JK8 MTR1B_HUMAN Modulator [8]
Melatonin receptor type 1A (MTNR1A) TT0WAIE MTR1A_HUMAN Modulator [8]
------------------------------------------------------------------------------------
Ramelteon Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [9]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Ramelteon Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [7]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Increases Expression [7]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Decreases Expression [7]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Decreases Expression [7]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Decreases Expression [7]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Increases Expression [7]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Decreases Expression [7]
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Decreases Expression [7]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DOT(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 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: 7937).
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: 1356).
4 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
5 Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4.
6 Abcg2 overexpression represents a novel mechanism for acquired resistance to the multi-kinase inhibitor Danusertib in BCR-ABL-positive cells in vitro. PLoS One. 2011 Apr 26;6(4):e19164. doi: 10.1371/journal.pone.0019164.
7 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
8 MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
9 Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91.
10 Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.