Details of the Drug Combination

General Information of Drug Combination (ID: DCTPS00)

• Drug Combination Name: Anastrozole + Uracil mustard
• Indication: Prostate carcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  Uracil mustard (DMHL7OB): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: PC-3
  Zero Interaction Potency (ZIP) Score: 3.04
  Bliss Independence Score: 9.03
  Loewe Additivity Score: 10.22
  LHighest Single Agent (HSA) Score: 10.88

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Anastrozole

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Estrogen-receptor positive breast cancer	N.A.	Approved	[3]
Obesity	5B81	Approved	[3]

Anastrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[6]

Anastrozole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Putative sodium-coupled neutral amino acid transporter 7 (SLC38A7)	DT2EGUN	S38A7_HUMAN	Substrate	[7]

Anastrozole Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[8]

Anastrozole Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[9]

Indication(s) of Uracil mustard

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[4]
Chronic myelogenous leukaemia	2A20.0	Approved	[5]
Polycythemia vera	2A20.4	Approved	[5]
Small lymphocytic lymphoma	2A82.0	Approved	[5]

Uracil mustard Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[10]

Uracil mustard Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1)	OT7FBG5W	NAR1_HUMAN	Increases ADR	[9]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC3LEMU	NCIH23	Investigative	[1]
Adenocarcinoma	DCVQB8O	A549	Investigative	[1]
Adenocarcinoma	DC545GU	HCT116	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCFQTZU	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCNJL0J	SR	Investigative	[1]
Astrocytoma	DCHW8YW	U251	Investigative	[1]
Astrocytoma	DCZTJRL	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCNSRPB	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCFG5PJ	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCSYQDF	786-0	Investigative	[1]
Cutaneous melanoma	DCNADW8	SK-MEL-5	Investigative	[1]
Glioma	DC4HPP3	SF-268	Investigative	[1]
Glioma	DCDD9JP	SF-295	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCIFYW7	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCBK06W	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DC3K006	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC2OEW9	EKVX	Investigative	[1]
Lung adenocarcinoma	DCMSRPM	NCI-H522	Investigative	[1]
Malignant melanoma	DC9232A	UACC62	Investigative	[1]
Malignant melanoma	DCX9A1W	LOX IMVI	Investigative	[1]
Melanoma	DCA47NA	SK-MEL-2	Investigative	[1]
Melanoma	DCHZ344	MALME-3M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCYUYP4	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DCYVQW4	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCAMKLC	SK-OV-3	Investigative	[1]
Renal cell carcinoma	DCVJKBU	UO-31	Investigative	[1]
Carcinoma	DC90XBP	RXF 393	Investigative	[11]
Colon carcinoma	DC7NM1L	KM12	Investigative	[11]
Invasive ductal carcinoma	DC31EML	T-47D	Investigative	[11]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] 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: 5137).
• [3] Anastrozole 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: 7621).
• [5] Uracil mustard FDA Label
• [6] Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
• [7] Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
• [8] In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
• [9] 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.
• [10] Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
• [11] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165