Details of the Drug Combination

General Information of Drug Combination (ID: DCKKQ3Y)

Drug Combination Name
Alvespimycin hydrochloride Artemether
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Alvespimycin hydrochloride   DM6KU93 Artemether   DM48QOT
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 7.912
Bliss Independence Score: 8.153
Loewe Additivity Score: 5.668
LHighest Single Agent (HSA) Score: 8.658

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Alvespimycin hydrochloride
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 1 [2]
Refractory hematologic malignancy 2A85.5 Phase 1 [2]
Alvespimycin hydrochloride Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Heat shock protein 90 alpha (HSP90A) TT78R5H HS90A_HUMAN Inhibitor [4]
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Indication(s) of Artemether
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [3]
Artemether Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sodium pump subunit alpha-1 (ATP1A1) TTWK8D0 AT1A1_HUMAN Binder [3]
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Artemether Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [5]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [6]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [8]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [9]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [6]
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⏷ Show the Full List of 6 DME(s)
Artemether Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 3 (NR1I3) OTS3SGH7 NR1I3_HUMAN Affects Expression [10]
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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 ClinicalTrials.gov (NCT00089271) 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas. U.S. National Institutes of Health.
3 The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
4 Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17-DMAG, KOS-1022) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jul;51(1):34-41.
5 The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999 Oct;66(4):408-14.
6 The contribution of the enzymes CYP2D6 and CYP2C19 in the demethylation of artemether in healthy subjects. Eur J Drug Metab Pharmacokinet. 1998 Jul-Sep;23(3):429-36.
7 Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women. Malar J. 2017 Jul 3;16(1):267.
8 Pharmacokinetic interaction between etravirine or darunavir/ritonavir and artemether/lumefantrine in healthy volunteers: a two-panel, two-way, two-period, randomized trial. HIV Med. 2013 Aug;14(7):421-9.
9 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
10 Fetal bovine serum and human constitutive androstane receptor: evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system. Toxicol Appl Pharmacol. 2014 Jun 1;277(2):221-30. doi: 10.1016/j.taap.2014.03.023. Epub 2014 Apr 12.