Details of the Drug Combination

General Information of Drug Combination (ID: DCJTJOR)

• Drug Combination Name: GS4071 + Trifluoperazine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  GS4071 (DMG0OUD): Small molecular drug
  Trifluoperazine (DMKBYWI): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 14.83
  Bliss Independence Score: 14.83
  Loewe Additivity Score: 25.62
  LHighest Single Agent (HSA) Score: 25.62

Molecular Interaction Atlas of This Drug Combination

Indication(s) of GS4071

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

GS4071 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Influenza Neuraminidase (Influ NA)	TT50QJ3	NRAM_I33A0	Inhibitor	[2]

Indication(s) of Trifluoperazine

Disease Entry	ICD 11	Status	REF
Anxiety	N.A.	Approved	[3]
Schizophrenia	6A20	Approved	[4]

Trifluoperazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Calmodulin (CALM)	TTV3NH6	CALM1_HUMAN; CALM2_HUMAN; CALM3_HUMAN	Inhibitor	[6]

Trifluoperazine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Trifluoperazine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
Dimethylaniline oxidase 2 (FMO2)	DEIASEZ	FMO2_HUMAN	Metabolism	[9]

Trifluoperazine Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Increases Oxidation	[9]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Activity	[10]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Affects Localization	[11]
Stonin-2 (STON2)	OT01JHHE	STON2_HUMAN	Decreases Expression	[12]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Increases ADR	[13]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Increases ADR	[13]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Increases ADR	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.
• [3] Trifluoperazine FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases. Food Chem Toxicol. 2016 Apr;90:112-22.
• [6] Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. Planta Med. 2003 Aug;69(8):692-5.
• [7] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [8] Psychotropic Medications Metabolized by Cytochromes P450 (CYP) 1A2 Enzyme and Relevant Drug Interactions: Review of Articles
• [9] Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis. Microb Cell Fact. 2015 Jun 12;14:82.
• [10] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
• [11] Rescue of Pink1 Deficiency by Stress-Dependent Activation of Autophagy. Cell Chem Biol. 2017 Apr 20;24(4):471-480.e4. doi: 10.1016/j.chembiol.2017.03.005. Epub 2017 Mar 30.
• [12] Stonin 2 activates lysosomal-mTOR axis for cell survival in oral cancer. Toxicol In Vitro. 2023 Apr;88:105561. doi: 10.1016/j.tiv.2023.105561. Epub 2023 Jan 23.
• [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.