Details of the Drug Combination

General Information of Drug Combination (ID: DCK36M3)

• Drug Combination Name: Anastrozole + Mechlorethamine
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  Mechlorethamine (DM0CVXA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-4
  Zero Interaction Potency (ZIP) Score: 4.5
  Bliss Independence Score: 5.64
  Loewe Additivity Score: 2.61
  LHighest Single Agent (HSA) Score: 5.42

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	[7]

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	[8]

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	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[9]

Anastrozole Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[10]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[11]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[12]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[13]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[14]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[15]

Indication(s) of Mechlorethamine

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Mycosis fungoides	2B01	Approved	[4]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[4]
Small lymphocytic lymphoma	2A82.0	Approved	[4]
T-cell lymphoma	2A90	Approved	[5]
Hodgkin lymphoma	2B30	Phase 3	[6]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]

Mechlorethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Intercalator	[18]

Mechlorethamine Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[19]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Activity	[20]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[21]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Activity	[22]
Glutathione S-transferase A2 (GSTA2)	OTW7UB1H	GSTA2_HUMAN	Increases Expression	[23]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[21]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[24]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Activity	[22]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[21]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[21]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Stability	[22]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[22]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Expression	[25]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[24]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[24]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Decreases Expression	[27]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[28]
Transient receptor potential cation channel subfamily A member 1 (TRPA1)	OTRDIR5M	TRPA1_HUMAN	Increases Response To Substance	[29]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCMJQUH	HL-60(TB)	Investigative	[1]
Chronic myelogenous leukemia	DCD4O0P	K-562	Investigative	[1]
Cutaneous melanoma	DCFGI3X	SK-MEL-5	Investigative	[1]
Malignant melanoma	DCR2GLB	LOX IMVI	Investigative	[1]
Malignant melanoma	DCHRSX5	UACC62	Investigative	[1]
Papillary renal cell carcinoma	DCVI2G8	ACHN	Investigative	[1]
Colon carcinoma	DCYXHU9	KM12	Investigative	[30]

References

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• [4] Mechlorethamine FDA Label
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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