Details of the Drug Combination

General Information of Drug Combination (ID: DCRHVLE)

• Drug Combination Name: Lefaxin + Acetazolamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Lefaxin (DM0CEY3): Small molecular drug
  Acetazolamide (DM1AF5U): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.88
  Bliss Independence Score: 9.88
  Loewe Additivity Score: 24.66
  LHighest Single Agent (HSA) Score: 24.67

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lefaxin

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

Lefaxin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[2]

Lefaxin Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Acetylcholinesterase (ACHE)	OT2H8HG6	ACES_HUMAN	Decreases Activity	[5]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Affects Expression	[6]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[6]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[6]
Glutathione peroxidase 1 (GPX1)	OTE2O72Q	GPX1_HUMAN	Decreases Expression	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[6]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[6]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Decreases Expression	[6]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[6]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[7]

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	[9]

Acetazolamide Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Carbonic anhydrase 12 (CA12)	OT6WNFU8	CAH12_HUMAN	Decreases Activity	[10]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[11]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Activity	[10]
Aquaporin-1 (AQP1)	OTX5MYX9	AQP1_HUMAN	Decreases Expression	[12]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[13]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[14]

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] Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
• [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] In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
• [6] The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
• [7] Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. doi: 10.1007/s00204-002-0328-8. Epub 2002 Mar 9.
• [8] Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure. Am J Nephrol. 1989;9(1):56-7. doi: 10.1159/000167936.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. J Med Chem. 2011 Oct 13;54(19):6905-18.
• [11] Indomethacin activates carbonic anhydrase and antagonizes the effect of the specific carbonic anhydrase inhibitor acetazolamide, by a direct mechanism of action. Int J Clin Pharmacol Ther. 2001 Jun;39(6):265-70.
• [12] [Effect of inhibiting aquaporin-1 on proliferation and apoptosis of the Hep-2 cell]. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006 Nov;20(21):988-91.
• [13] 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.
• [14] 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.