Details of the Drug Combination

General Information of Drug Combination (ID: DCZNBGZ)

• Drug Combination Name: Emetine + Acetazolamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Emetine (DMCT2YF): Small molecular drug
  Acetazolamide (DM1AF5U): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.15
  Bliss Independence Score: 8.15
  Loewe Additivity Score: 10.06
  LHighest Single Agent (HSA) Score: 10.07

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Emetine

Disease Entry	ICD 11	Status	REF
Hepatitis virus infection	1E50-1E51	Approved	[2]

Emetine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Emetine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Emetine Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)	OT9QIHEQ	RECK_HUMAN	Decreases Expression	[8]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[9]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Decreases Expression	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[5]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Decreases Expression	[5]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Decreases Expression	[5]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[5]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Expression	[5]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[8]

Indication(s) of Acetazolamide

Disease Entry	ICD 11	Status	REF
Absence epilepsy	N.A.	Approved	[3]
Altitude sickness	N.A.	Approved	[3]
Edema	MG29	Approved	[3]
Glaucoma/ocular hypertension	9C61	Approved	[4]

Acetazolamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Carbonic anhydrase I (CA-I)	TTHQPL7	CAH1_HUMAN	Modulator	[12]

Acetazolamide Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Decreases Activity	[13]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Activity	[13]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[14]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[15]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Acetazolamide 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: 6792).
• [5] Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
• [6] Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
• [7] Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities. Biol Pharm Bull. 2001 Jun;24(6):678-82.
• [8] Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
• [9] Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
• [10] Apoptosis induces Bcl-XS and cleaved Bcl-XL in chronic lymphocytic leukaemia. Biochem Biophys Res Commun. 2011 Feb 18;405(3):480-5. doi: 10.1016/j.bbrc.2011.01.057. Epub 2011 Jan 20.
• [11] Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure. Am J Nephrol. 1989;9(1):56-7. doi: 10.1159/000167936.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. J Med Chem. 2011 Oct 13;54(19):6905-18.
• [14] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [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.