Details of the Drug Combination

General Information of Drug Combination (ID: DCUCWCT)

• Drug Combination Name: Anastrozole + Pomalidomide
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Anastrozole (DMNP60F): Small molecular drug
  Pomalidomide (DMTGBAX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 1.54
  Bliss Independence Score: 9.43
  Loewe Additivity Score: 7.81
  LHighest Single Agent (HSA) Score: 8.27

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 Pomalidomide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[4]
Systemic sclerosis	4A42	Approved	[5]

Pomalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiogenesis/myeloma cell growth (AMCG)	TTDIBYJ	NOUNIPROTAC	Modulator	[15]

Pomalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[16]

Pomalidomide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[17]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[18]

Pomalidomide Interacts with 27 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Oxidation	[19]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Secretion	[20]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Secretion	[20]
Granulocyte colony-stimulating factor (CSF3)	OT9GC6TP	CSF3_HUMAN	Increases Secretion	[20]
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Decreases Expression	[21]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[20]
Erythroid transcription factor (GATA1)	OTX1R7O1	GATA1_HUMAN	Decreases Expression	[20]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Expression	[20]
Transcription factor PU.1 (SPI1)	OTVCA1D0	SPI1_HUMAN	Increases Expression	[20]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[20]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Affects Expression	[21]
Endothelial transcription factor GATA-2 (GATA2)	OTBP2QQ2	GATA2_HUMAN	Decreases Expression	[20]
Rhombotin-2 (LMO2)	OTCC370G	RBTN2_HUMAN	Decreases Expression	[20]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Decreases Secretion	[20]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Increases Expression	[20]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[20]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[20]
DNA-binding protein inhibitor ID-2 (ID2)	OT0U1D53	ID2_HUMAN	Increases Expression	[20]
Krueppel-like factor 1 (KLF1)	OT1FK08U	KLF1_HUMAN	Decreases Expression	[20]
CCAAT/enhancer-binding protein epsilon (CEBPE)	OTKZA25M	CEBPE_HUMAN	Increases Expression	[20]
Transcription factor NF-E2 45 kDa subunit (NFE2)	OTLM94BI	NFE2_HUMAN	Decreases Expression	[20]
Zinc finger protein Gfi-1b (GFI1B)	OTRDW8YO	GFI1B_HUMAN	Decreases Expression	[20]
Zinc finger protein Gfi-1 (GFI1)	OT9HB9H8	GFI1_HUMAN	Increases Expression	[20]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[22]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[19]
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Increases Oxidation	[19]
Protein cereblon (CRBN)	OTXH9MDC	CRBN_HUMAN	Increases Response To Substance	[23]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCPO570	NCIH23	Investigative	[1]
Astrocytoma	DC44B5Z	SNB-19	Investigative	[1]
Chronic myelogenous leukemia	DC7L87U	K-562	Investigative	[1]
Cutaneous melanoma	DCDFF63	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCW6G7W	OVCAR-5	Investigative	[1]
Renal cell carcinoma	DCOBHUC	UO-31	Investigative	[1]
Renal cell carcinoma	DCLP0TM	SN12C	Investigative	[1]
Carcinoma	DC4ABE3	MCF7	Investigative	[24]
Colon adenocarcinoma	DCOM3MI	COLO 205	Investigative	[24]
Invasive ductal carcinoma	DC8KVYX	HS 578T	Investigative	[24]
Invasive ductal carcinoma	DC8QLUO	BT-549	Investigative	[24]
Invasive ductal carcinoma	DC5TSQG	T-47D	Investigative	[24]

References

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• [3] Anastrozole FDA Label
• [4] Pomalidomide FDA Label
• [5] 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: 7348).
• [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.
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• [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] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
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• [17] Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
• [18] Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
• [19] Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.
• [20] Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
• [21] Thalidomide and Its Analogs Differentially Target Fibroblast Growth Factor Receptors: Thalidomide Suppresses FGFR Gene Expression while Pomalidomide Dampens FGFR2 Activity. Chem Res Toxicol. 2019 Apr 15;32(4):589-602. doi: 10.1021/acs.chemrestox.8b00286. Epub 2019 Mar 15.
• [22] Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
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