Details of the Drug Combination

General Information of Drug Combination (ID: DC9ZSUV)

• Drug Combination Name: Letrozole + Tamoxifen
• Indication: Breast Cancer; Status: Phase 2 [1]
• Component Drugs:
  Letrozole (DMH07Y3): Small molecular drug
  Tamoxifen (DMLB0EZ): Small molecular drug

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	[6]

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	[7]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[8]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[9]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[10]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[11]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[11]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[12]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[13]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[14]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[14]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[15]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[13]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[16]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[17]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[17]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[18]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[13]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[15]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[17]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[19]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[13]

Indication(s) of Tamoxifen

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Inflammatory breast cancer	2C62	Approved	[5]
Invasive ductal breast carcinoma	N.A.	Approved	[5]

Tamoxifen Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Antagonist	[20]

Tamoxifen Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[21]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[22]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[23]

Tamoxifen Interacts with 16 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[24]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[25]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[26]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[27]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[28]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[29]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[30]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[31]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[27]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[32]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[33]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[34]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[35]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[36]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[37]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[38]

Tamoxifen Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Coagulation factor V (F5)	OTDMZ3LT	FA5_HUMAN	Increases ADR	[39]

References

• [1] ClinicalTrials.gov (NCT02764541) Palbociclib and Endocrine Therapy for LObular Breast Cancer Preoperative Study (PELOPS)
• [2] Letrozole FDA Label
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• [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: 1016).
• [5] Tamoxifen FDA Label
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