Details of the Drug Combination

General Information of Drug Combination (ID: DC1KVTG)

• Drug Combination Name: Indazole derivative 5 + Letrozole
• Indication: Lung adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Indazole derivative 5 (DMM1I8R): Small molecular drug
  Letrozole (DMH07Y3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HOP-62
  Zero Interaction Potency (ZIP) Score: 1.27
  Bliss Independence Score: 3.59
  Loewe Additivity Score: 1.87
  LHighest Single Agent (HSA) Score: 0.29

Molecular Interaction Atlas of This Drug Combination

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[4]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[4]

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	[5]

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	[6]
Aromatase (CYP19A1)	DEQX145	CP19A_HUMAN	Metabolism	[7]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[8]

Letrozole Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[9]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[10]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Oxidation	[10]
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[11]
Dickkopf-related protein 1 (DKK1)	OTRDLUSP	DKK1_HUMAN	Increases Expression	[12]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[13]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[13]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[14]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[12]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[15]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[16]
G1/S-specific cyclin-D2 (CCND2)	OTDULQF9	CCND2_HUMAN	Decreases Expression	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[17]
Leukemia inhibitory factor receptor (LIFR)	OT36W9O5	LIFR_HUMAN	Increases Expression	[12]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[14]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[16]
Lanosterol 14-alpha demethylase (CYP51A1)	OTAYHG9C	CP51A_HUMAN	Decreases Activity	[18]
Fibroblast growth factor 22 (FGF22)	OTVIX6J0	FGF22_HUMAN	Increases Expression	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Colon adenocarcinoma	DCBVMI1	COLO 205	Investigative	[19]
Invasive ductal carcinoma	DCA5D92	T-47D	Investigative	[19]
Invasive ductal carcinoma	DCGHF9E	BT-549	Investigative	[19]
Cutaneous melanoma	DCP3KFD	SK-MEL-28	Investigative	[1]
Cutaneous melanoma	DC4TFZV	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC9RXDP	OVCAR-8	Investigative	[1]
Melanoma	DCM8JXE	MALME-3M	Investigative	[1]
Melanoma	DCB2K6O	UACC-257	Investigative	[1]

References

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• [2] Letrozole FDA Label
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• [12] Clomiphene citrate versus letrozole: molecular analysis of the endometrium in women with polycystic ovary syndrome. Fertil Steril. 2011 Oct;96(4):1051-6. doi: 10.1016/j.fertnstert.2011.07.1092.
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