Details of the Drug Combination

General Information of Drug Combination (ID: DCHR4L5)

• Drug Combination Name: Anastrozole + BIO-300
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  BIO-300 (DMJ7NVI): N.A.
• High-throughput Screening Result:
  Testing Cell Line: HT29
  Zero Interaction Potency (ZIP) Score: 3.45
  Bliss Independence Score: 3.57
  Loewe Additivity Score: 4.78
  LHighest Single Agent (HSA) Score: 6.07

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	[6]

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	[7]

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	[8]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[8]

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	[9]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[10]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[11]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Decreases Activity	[12]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Decreases Expression	[13]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[14]

Indication(s) of BIO-300

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
Rheumatoid arthritis	FA20	Phase 1	[5]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCW1MKK	OVCAR3	Investigative	[1]
Adenocarcinoma	DCWD6PD	HCT116	Investigative	[1]
Adult acute myeloid leukemia	DCBDWPI	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC9XDVA	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCXDPNQ	SR	Investigative	[1]
Astrocytoma	DCEQNKL	U251	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DC5H0RE	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCYEZWV	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DC9V2O1	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DCNE4OV	A498	Investigative	[1]
Clear cell renal cell carcinoma	DC0NMKL	786-0	Investigative	[1]
Cutaneous melanoma	DC6WDNA	SK-MEL-28	Investigative	[1]
Cutaneous melanoma	DC0F0W4	SK-MEL-5	Investigative	[1]
Glioma	DCUCYMK	SF-539	Investigative	[1]
Glioma	DCY41ZS	SF-295	Investigative	[1]
Glioma	DCNNTFC	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC3B8AP	OVCAR-4	Investigative	[1]
Large cell lung carcinoma	DCJCC1H	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC3524J	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DC7402G	HOP-62	Investigative	[1]
Malignant melanoma	DCHLZYZ	UACC62	Investigative	[1]
Malignant melanoma	DC9XCKG	LOX IMVI	Investigative	[1]
Melanoma	DC7VC4P	UACC-257	Investigative	[1]
Melanoma	DCDTAMI	MALME-3M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCO48KT	IGROV1	Investigative	[1]
Papillary renal cell carcinoma	DCZYORF	ACHN	Investigative	[1]
Plasma cell myeloma	DC1A20Y	RPMI-8226	Investigative	[1]
Pleural epithelioid mesothelioma	DC0HOY3	NCI-H226	Investigative	[1]
Prostate carcinoma	DC3WP63	PC-3	Investigative	[1]
Breast adenocarcinoma	DCRXEXJ	MDA-MB-468	Investigative	[15]
Carcinoma	DC591OB	RXF 393	Investigative	[15]
Colon adenocarcinoma	DCSLGFL	COLO 205	Investigative	[15]
Colon carcinoma	DCDI826	KM12	Investigative	[15]
Invasive ductal carcinoma	DCT6OP4	HS 578T	Investigative	[15]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [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] Clinical pipeline report, company report or official report of Humanetics.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] 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.
• [7] Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2. Clin Pharmacol Ther. 2019 Jan 16.
• [8] In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
• [9] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [10] 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.
• [11] Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res. 2005 Apr 15;11(8):2809-21. doi: 10.1158/1078-0432.CCR-04-2187.
• [12] 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.
• [13] 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.
• [14] 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.
• [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.