Details of the Drug Combination

General Information of Drug Combination (ID: DCKSS77)

• Drug Combination Name: Letrozole + Mercaptopurine
• Indication: Plasma cell myeloma; Status: Investigative [1]
• Component Drugs:
  Letrozole (DMH07Y3): Small molecular drug
  Mercaptopurine (DMTM2IK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RPMI-8226
  Zero Interaction Potency (ZIP) Score: 2.11
  Bliss Independence Score: 2.08
  Loewe Additivity Score: 2.2
  LHighest Single Agent (HSA) Score: 5.16

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Letrozole

Disease Entry	ICD 11	Status	REF
Estrogen-receptor positive breast cancer	N.A.	Approved	[2]
Hormonally-responsive breast cancer	2C60-2C65	Approved	[3]

Letrozole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[8]

Letrozole Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[10]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[11]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[13]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[13]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[14]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[15]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[16]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[16]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[17]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[15]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[18]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[19]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[19]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[20]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[15]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[17]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[19]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[21]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[15]

Indication(s) of Mercaptopurine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[4]
Acute lymphocytic leukaemia	2B33.3	Approved	[5]
Crohn disease	DD70	Phase 4	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[7]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[7]

Mercaptopurine Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MERS-CoV papain-like proteinase (PL-PRO)	TTYJOLE	R1AB_CVEMC (854-2740)	Inhibitor	[7]
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[24]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[7]
Amidophosphoribosyltransferase (PPAT)	TTZFTY4	PUR1_HUMAN	Breaker	[25]

Mercaptopurine Interacts with 9 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[26]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[27]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[28]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[29]
Concentrative nucleoside transporter 2 (SLC28A2)	DT82KPY	S28A2_HUMAN	Substrate	[30]
Concentrative Na(+)-nucleoside cotransporter 3 (SLC28A3)	DT4YL5R	S28A3_HUMAN	Substrate	[31]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[30]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[30]
Equilibrative nucleobase transporter 1 (SLC43A3)	DTGBPR5	S43A3_HUMAN	Substrate	[32]

Mercaptopurine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[33]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[33]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[34]

Mercaptopurine Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Affects Response To Substance	[35]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Increases ADR	[14]
Thiopurine S-methyltransferase (TPMT)	OTFOX70W	TPMT_HUMAN	Decreases Metabolism	[36]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[37]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Increases Expression	[37]
Glutathione peroxidase 2 (GPX2)	OTXI2NTI	GPX2_HUMAN	Increases Expression	[37]
Glutathione peroxidase 3 (GPX3)	OT6PK94R	GPX3_HUMAN	Increases Expression	[37]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[37]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[37]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Affects Localization	[38]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[39]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Decreases Phosphorylation	[22]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[22]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[22]
Molybdenum cofactor sulfurase (MOCOS)	OT0TL3Q5	MOCOS_HUMAN	Decreases Oxidation	[40]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Affects Response To Substance	[41]
Major vault protein (MVP)	OTJGHJRB	MVP_HUMAN	Decreases Response To Substance	[42]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Response To Substance	[41]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[23]
Nucleotide triphosphate diphosphatase NUDT15 (NUDT15)	OTX8SZOT	NUD15_HUMAN	Increases Response To Substance	[43]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCCJJFI	HCC-2998	Investigative	[1]
Glioma	DCLPI78	SF-268	Investigative	[1]
Lung adenocarcinoma	DCQKOND	HOP-62	Investigative	[1]
Pleural epithelioid mesothelioma	DCJH8G2	NCI-H226	Investigative	[1]

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