Details of the Drug Combination

General Information of Drug Combination (ID: DCTHZI4)

• Drug Combination Name: Artemether + Omacetaxine mepesuccinate
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Artemether (DM48QOT): Small molecular drug
  Omacetaxine mepesuccinate (DMPU2WX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 17.076
  Bliss Independence Score: 16.481
  Loewe Additivity Score: 5.917
  LHighest Single Agent (HSA) Score: 10.055

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Artemether

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

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	[2]

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]

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]

Indication(s) of Omacetaxine mepesuccinate

Disease Entry	ICD 11	Status	REF
Adult acute monocytic leukemia	N.A.	Approved	[3]
Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Chronic myeloid leukaemia	2A20	Approved	[4]
Leukemia	N.A.	Approved	[3]

Omacetaxine mepesuccinate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ribosome A (hRA)	TTA4FIU	NOUNIPROTAC	Modulator	[11]

Omacetaxine mepesuccinate Interacts with 29 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK)	OTLF4ZB1	IKKA_HUMAN	Increases Phosphorylation	[12]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Expression	[13]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[14]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[13]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[13]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Increases Expression	[13]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Expression	[13]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[13]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[13]
Hematopoietic progenitor cell antigen CD34 (CD34)	OT1MOFLZ	CD34_HUMAN	Decreases Expression	[12]
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38)	OTG0TTX7	CD38_HUMAN	Increases Expression	[12]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[13]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[13]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[13]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[13]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Increases Expression	[12]
Ephrin type-B receptor 4 (EPHB4)	OTKLPVXJ	EPHB4_HUMAN	Decreases Expression	[13]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Cleavage	[13]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[13]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[13]
Nuclear factor NF-kappa-B p100 subunit (NFKB2)	OTS231V7	NFKB2_HUMAN	Increases Expression	[12]
Transcription factor RelB (RELB)	OTU3QYEF	RELB_HUMAN	Increases Expression	[12]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[12]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[14]
Jouberin (AHI1)	OT8K2YWY	AHI1_HUMAN	Increases Expression	[15]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[13]

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] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [3] Omacetaxine mepesuccinate FDA Label
• [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: 7454).
• [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.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [12] Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
• [13] Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
• [14] [Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013 Jun;33(6):834-9.
• [15] [Expression and function of Ahi-1 gene in Jurkat cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):445-9.