Details of the Drug Combination

General Information of Drug Combination (ID: DCUCBEQ)

• Drug Combination Name: Ciprofibrate + Acetazolamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ciprofibrate (DMGC5DB): Small molecular drug
  Acetazolamide (DM1AF5U): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.38
  Bliss Independence Score: 11.38
  Loewe Additivity Score: 26.38
  LHighest Single Agent (HSA) Score: 26.38

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ciprofibrate

Disease Entry	ICD 11	Status	REF
Hyperlipoproteinemia	5C80	Approved	[2]

Ciprofibrate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Agonist	[5]

Ciprofibrate Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]

Ciprofibrate Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Increases Activity	[7]
Sulfotransferase 2A1 (SULT2A1)	OT0ISKQ4	ST2A1_HUMAN	Increases Expression	[8]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Activity	[9]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Decreases Expression	[10]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Increases Expression	[11]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Decreases Expression	[11]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[11]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)	OTM0A0DY	ACOX1_HUMAN	Increases Expression	[12]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[13]

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	[15]

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	[16]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[17]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Activity	[16]
Aquaporin-1 (AQP1)	OTX5MYX9	AQP1_HUMAN	Decreases Expression	[18]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[19]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[20]

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: 3438).
• [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] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [6] Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62.
• [7] Currently available hypolipidaemic drugs and future therapeutic developments. Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47.
• [8] Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor. Mol Pharmacol. 2005 Apr;67(4):1257-67.
• [9] Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers. Eur J Pharmacol. 2008 Apr 28;584(2-3):213-21.
• [10] Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem. 1994 Dec 9;269(49):31012-8.
• [11] Peroxisome proliferator-activated receptor ligands affect growth-related gene expression in human leukemic cells. J Pharmacol Exp Ther. 2003 Jun;305(3):932-42. doi: 10.1124/jpet.103.049098. Epub 2003 Mar 20.
• [12] Fish oil and fenofibrate prevented phosphorylation-dependent hepatic sortilin 1 degradation in Western diet-fed mice. J Biol Chem. 2014 Aug 8;289(32):22437-49. doi: 10.1074/jbc.M114.548933. Epub 2014 Jul 1.
• [13] Role of Peroxisome Proliferator-Activated Receptor / and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells. PPAR Res. 2013;2013:121956. doi: 10.1155/2013/121956. Epub 2013 May 2.
• [14] Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure. Am J Nephrol. 1989;9(1):56-7. doi: 10.1159/000167936.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. J Med Chem. 2011 Oct 13;54(19):6905-18.
• [17] 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.
• [18] [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.
• [19] 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.
• [20] 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.