Details of the Drug Combination

General Information of Drug Combination (ID: DCCTFOF)

• Drug Combination Name: 2-Propanol, Isopropanol + Ondansetron
• Indication: Nausea; Status: Phase 4 [1]
• Component Drugs:
  2-Propanol, Isopropanol (DML5O0H): Small molecular drug
  Ondansetron (DMOTQ1I): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of 2-Propanol, Isopropanol

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

2-Propanol, Isopropanol Interacts with 7 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nitric-oxide synthase endothelial (NOS3)	TTCM4B3	NOS3_HUMAN	Inhibitor	[2]
Oxysterols receptor LXR-beta (NR1H2)	TTXA6PH	NR1H2_HUMAN	Inhibitor	[2]
Group IIA phospholipase A2 (GIIA sPLA2)	TTO8QRU	PA2GA_HUMAN	Inhibitor	[6]
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Inhibitor	[6]
Heme oxygenase 1 (HMOX1)	TTI6V2A	HMOX1_HUMAN	Inhibitor	[2]
GTP cyclohydrolase-I (GCH1)	TTLSWP6	GCH1_HUMAN	Inhibitor	[6]
Adenosylhomocysteinase (AHCY)	TTE2KUJ	SAHH_HUMAN	Inhibitor	[6]

2-Propanol, Isopropanol Interacts with 25 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Transcription factor MafG (MAFG)	OTBQFUZH	MAFG_HUMAN	Increases Expression	[5]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[5]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases Expression	[5]
Ferritin light chain (FTL)	OTYQA8A6	FRIL_HUMAN	Increases Expression	[5]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Increases Expression	[5]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Increases Expression	[5]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[5]
Ferrochelatase, mitochondrial (FECH)	OTDWEI6C	HEMH_HUMAN	Increases Expression	[5]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Expression	[5]
NADP-dependent malic enzyme (ME1)	OTSVEUQE	MAOX_HUMAN	Increases Expression	[5]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[5]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[5]
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Increases Expression	[5]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Increases Expression	[5]
Prostaglandin reductase 1 (PTGR1)	OTMAR351	PTGR1_HUMAN	Increases Expression	[5]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[5]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Decreases Activity	[7]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Affects Folding	[8]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Decreases Activity	[7]
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HADH)	OTJDOL20	HCDH_HUMAN	Increases Metabolism	[9]
All-trans-retinol dehydrogenase ADH4 (ADH4)	OTKDKKNG	ADH4_HUMAN	Increases Oxidation	[10]
Alcohol dehydrogenase 1C (ADH1C)	OTO1DV7F	ADH1G_HUMAN	Increases Oxidation	[10]
All-trans-retinol dehydrogenase ADH7 (ADH7)	OTO2ZATJ	ADH7_HUMAN	Increases Oxidation	[10]
Alcohol dehydrogenase 1A (ADH1A)	OTTS983E	ADH1A_HUMAN	Increases Oxidation	[10]
All-trans-retinol dehydrogenase ADH1B (ADH1B)	OTV3TB81	ADH1B_HUMAN	Increases Oxidation	[10]

Indication(s) of Ondansetron

Disease Entry	ICD 11	Status	REF
Chemotherapy-induced nausea	MD90	Approved	[3]
Malignant glioma	2A00.0	Approved	[4]
Nausea	MD90	Approved	[4]
Vomiting	MD90	Approved	[4]
Alcohol dependence	6C40.2	Phase 2	[3]
Gastroenteritis	N.A.	Investigative	[4]

Ondansetron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3 receptor (5HT3R)	TTNXLKE	NOUNIPROTAC	Agonist	[11]

Ondansetron Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Ondansetron Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[16]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[17]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[18]

Ondansetron Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[19]

References

• [1] ClinicalTrials.gov (NCT02760069) Isopropyl Alcohol vs Ondansetron for Nausea in the Emergency Department
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] 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: 2290).
• [4] Ondansetron FDA Label
• [5] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
• [6] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [7] The dysregulation of the monocyte/macrophage effector function induced by isopropanol is mediated by the defective activation of distinct members of the AP-1 family of transcription factors. Toxicol Sci. 2012 Jan;125(1):144-56. doi: 10.1093/toxsci/kfr283. Epub 2011 Oct 20.
• [8] Metal-catalyzed oxidation of human growth hormone: modulation by solvent-induced changes of protein conformation. J Pharm Sci. 2001 Jan;90(1):58-69. doi: 10.1002/1520-6017(200101)90:1<58::aid-jps7>3.0.co;2-w.
• [9] Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase. Biochem J. 2000 Jan 1;345 Pt 1(Pt 1):139-43.
• [10] Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole. Chem Biol Interact. 2011 May 30;191(1-3):26-31. doi: 10.1016/j.cbi.2010.12.005. Epub 2010 Dec 15.
• [11] Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial. Eur J Gastroenterol Hepatol. 1998 Oct;10(10):865-70.
• [12] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [13] The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999 Apr;65(4):377-81.
• [14] Effects of serotonin-3 receptor antagonists on cytochrome P450 activities in human liver microsomes. Biol Pharm Bull. 2006 Sep;29(9):1931-5.
• [15] Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.
• [16] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos. 1995 Nov;23(11):1225-30.
• [17] Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos. 1996 May;24(5):602-9.
• [18] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [19] Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-B downregulation. Cell Biol Toxicol. 2023 Jun;39(3):1119-1135. doi: 10.1007/s10565-021-09667-0. Epub 2021 Oct 15.