Details of the Drug Combination

General Information of Drug Combination (ID: DCRP127)

• Drug Combination Name: NABILONE + Acetazolamide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  NABILONE (DMVRYT2): Small molecular drug
  Acetazolamide (DM1AF5U): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 14.56
  Bliss Independence Score: 14.56
  Loewe Additivity Score: 26.37
  LHighest Single Agent (HSA) Score: 26.37

Molecular Interaction Atlas of This Drug Combination

Indication(s) of NABILONE

Disease Entry	ICD 11	Status	REF
Insomnia	7A00-7A0Z	Approved	[2]

NABILONE Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cannabinoid receptor 2 (CB2)	TTMSFAW	CNR2_HUMAN	Inhibitor	[5]
Cannabinoid receptor 1 (CB1)	TT6OEDT	CNR1_HUMAN	Inhibitor	[5]

NABILONE Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cannabinoid receptor 2 (CNR2)	OTYP9P43	CNR2_HUMAN	Affects Binding	[6]

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	[8]

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	[9]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[10]
Carbonic anhydrase 9 (CA9)	OTNA51XT	CAH9_HUMAN	Decreases Activity	[9]
Aquaporin-1 (AQP1)	OTX5MYX9	AQP1_HUMAN	Decreases Expression	[11]
Rho GTPase-activating protein 45 (ARHGAP45)	OTL86FEQ	HMHA1_HUMAN	Affects Expression	[12]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Increases ADR	[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] 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] Novel 1',1'-chain substituted hexahydrocannabinols: 9-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid r... J Med Chem. 2010 Oct 14;53(19):6996-7010.
• [6] Cloning and pharmacological characterization of the dog cannabinoid CB?receptor. Eur J Pharmacol. 2011 Nov 1;669(1-3):24-31. doi: 10.1016/j.ejphar.2011.08.002. Epub 2011 Aug 19.
• [7] Tamm-Horsfall protein accumulation in glomeruli during acetazolamide-induced acute renal failure. Am J Nephrol. 1989;9(1):56-7. doi: 10.1159/000167936.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. J Med Chem. 2011 Oct 13;54(19):6905-18.
• [10] 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.
• [11] [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.
• [12] 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.
• [13] 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.