Details of the Drug Combination

General Information of Drug Combination (ID: DCPGLMJ)

• Drug Combination Name: Estramustine + Mepacrine
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  Mepacrine (DMU8L7C): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR3
  Zero Interaction Potency (ZIP) Score: 4.35
  Bliss Independence Score: 8.9
  Loewe Additivity Score: 0
  LHighest Single Agent (HSA) Score: 0.93

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Estramustine

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

Estramustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estramustine binding protein (EMBP)	TTSBFYK	NOUNIPROTAC	Binder	[4]

Estramustine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]

Estramustine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[6]

Indication(s) of Mepacrine

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

Mepacrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Inhibitor	[3]

Mepacrine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]

Mepacrine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]

Mepacrine Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[9]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[10]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1)	OTSBQR6D	PLCG1_HUMAN	Decreases Phosphorylation	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[10]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[10]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[12]
Casein kinase I isoform alpha (CSNK1A1)	OTJ6O1IC	KC1A_HUMAN	Increases Expression	[9]
Forkhead box protein P3 (FOXP3)	OTA9Z9OC	FOXP3_HUMAN	Increases Expression	[10]
F-box/WD repeat-containing protein 1A (BTRC)	OT2EZDGR	FBW1A_HUMAN	Decreases Expression	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Transport	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Colon carcinoma	DCCMPTG	KM12	Investigative	[13]
Adenocarcinoma	DCO7QWE	SW-620	Investigative	[1]
Adenocarcinoma	DCQPNAT	HCT116	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCDJN9W	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCZWKDR	NCI\\/ADR-RES	Investigative	[1]
Melanoma	DCR889E	SK-MEL-2	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.
• [4] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [5] Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.
• [6] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [7] Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
• [8] Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its brain accumulation is limited by P-glycoprotein. Drug Metab Dispos. 2006 Jul;34(7):1136-44.
• [9] Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and catenin through activation of GSK3. Toxicol Appl Pharmacol. 2017 Sep 1;330:53-64. doi: 10.1016/j.taap.2017.07.008. Epub 2017 Jul 15.
• [10] Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/-TrCP/SP1 axis-mediated BAX upregulation. Toxicol Appl Pharmacol. 2017 Nov 1;334:35-46. doi: 10.1016/j.taap.2017.08.019. Epub 2017 Sep 1.
• [11] Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK. Toxicol In Vitro. 2022 Sep;83:105420. doi: 10.1016/j.tiv.2022.105420. Epub 2022 Jun 17.
• [12] Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action. Arch Toxicol. 2021 Jan;95(1):321-336. doi: 10.1007/s00204-020-02902-3. Epub 2020 Sep 10.
• [13] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165