Details of the Drug Combination

General Information of Drug Combination (ID: DC1ID42)

• Drug Combination Name: Anastrozole + ER819762
• Indication: Renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  ER819762 (DMSG91J): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: UO-31
  Zero Interaction Potency (ZIP) Score: 0.63
  Bliss Independence Score: 0.35
  Loewe Additivity Score: 0.44
  LHighest Single Agent (HSA) Score: 0.21

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	[5]

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	[6]

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	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[7]

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	[8]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[9]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[10]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[11]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[12]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[13]

Indication(s) of ER819762

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[4]

ER819762 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin E2 receptor EP4 (PTGER4)	TT79WV3	PE2R4_HUMAN	Antagonist	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCJDF75	OVCAR3	Investigative	[1]
Adenocarcinoma	DC8VAV9	NCIH23	Investigative	[1]
Adenocarcinoma	DCUB61R	A549	Investigative	[1]
Adenocarcinoma	DC90OOZ	HCT116	Investigative	[1]
Adult acute myeloid leukemia	DCVHZ1T	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCQKV2N	MOLT-4	Investigative	[1]
Amelanotic melanoma	DCOA0S0	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DCQUGZE	M14	Investigative	[1]
Astrocytoma	DC4N68Y	U251	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCR8CX4	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCSWWTU	A498	Investigative	[1]
Clear cell renal cell carcinoma	DC4GOQ4	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC6DNWM	TK-10	Investigative	[1]
Cutaneous melanoma	DCI8B6Z	SK-MEL-28	Investigative	[1]
Glioma	DCIX5UB	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC870JH	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC9ELII	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DC9FC9C	EKVX	Investigative	[1]
Lung adenocarcinoma	DCZPCKS	NCI-H522	Investigative	[1]
Malignant melanoma	DC9UTZ7	LOX IMVI	Investigative	[1]
Malignant melanoma	DCWILOG	UACC62	Investigative	[1]
Melanoma	DCQW4AN	SK-MEL-2	Investigative	[1]
Melanoma	DC9C17K	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCKUALD	NCI-H322M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCDGR3U	SK-OV-3	Investigative	[1]
Plasma cell myeloma	DCP65TF	RPMI-8226	Investigative	[1]
Prostate carcinoma	DCDSU89	PC-3	Investigative	[1]
Renal cell carcinoma	DCIP2HI	SN12C	Investigative	[1]
Breast adenocarcinoma	DCK1RKY	MDA-MB-468	Investigative	[15]
Colon adenocarcinoma	DCF8X2J	COLO 205	Investigative	[15]
Invasive ductal carcinoma	DCRTR6D	HS 578T	Investigative	[15]
Invasive ductal carcinoma	DCU6OLM	BT-549	Investigative	[15]

References

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• [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: 4040).
• [5] 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.
• [6] Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
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• [9] Aromatase inhibitors: cellular and molecular effects. J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. doi: 10.1016/j.jsbmb.2005.04.010.
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• [11] Assessment of Five Pesticides as Endocrine-Disrupting Chemicals: Effects on Estrogen Receptors and Aromatase. Int J Environ Res Public Health. 2022 Feb 10;19(4):1959. doi: 10.3390/ijerph19041959.
• [12] Inhibition of estrogen receptor reduces connexin 43 expression in breast cancers. Toxicol Appl Pharmacol. 2018 Jan 1;338:182-190. doi: 10.1016/j.taap.2017.11.020. Epub 2017 Nov 24.
• [13] Biomarker changes during neoadjuvant anastrozole, tamoxifen, or the combination: influence of hormonal status and HER-2 in breast cancer--a study from the IMPACT trialists. J Clin Oncol. 2005 Apr 10;23(11):2477-92. doi: 10.1200/JCO.2005.07.559. Epub 2005 Mar 14.
• [14] A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310.
• [15] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.