Details of the Drug Combination

General Information of Drug Combination (ID: DCLKMFO)

• Drug Combination Name: Pepstatin + Tropisetron
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pepstatin (DM9S1EA): Small molecular drug
  Tropisetron (DMNSJ7V): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.34
  Bliss Independence Score: 2.34
  Loewe Additivity Score: 14.88
  LHighest Single Agent (HSA) Score: 14.88

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pepstatin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Terminated	[2]

Pepstatin Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)	TT7EASG	Q9N6S8_PLAFA	Inhibitor	[4]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[5]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[5]
Plasmodium Cysteine protease falcipain (Malaria CPF)	TTJNPTK	NOUNIPROTAC	Inhibitor	[5]

Pepstatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Decreases Activity	[6]

Indication(s) of Tropisetron

Disease Entry	ICD 11	Status	REF
Fibromyalgia	MG30.01	Approved	[3]

Tropisetron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[7]

Tropisetron Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Tropisetron Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[11]

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004280)
• [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: 260).
• [4] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [5] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [6] Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells. Cell Death Differ. 2001 May;8(5):477-85. doi: 10.1038/sj.cdd.4400843.
• [7] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [8] 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.
• [9] 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.
• [10] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [11] 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.