Details of the Drug Combination

General Information of Drug Combination (ID: DCCY9G1)

Drug Combination Name

Norcisapride Pomalidomide

Indication

Disease Entry	Status	REF
Chronic myelogenous leukemia	Investigative	[1]

Component Drugs

Norcisapride DMJSKUI

Pomalidomide DMTGBAX

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: KBM-7

Zero Interaction Potency (ZIP) Score: 6.93

Bliss Independence Score: 6.93

Loewe Additivity Score: 21.94

LHighest Single Agent (HSA) Score: 21.94

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Norcisapride

Disease Entry	ICD 11	Status	REF
Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[2]

Norcisapride Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 4 receptor (HTR4)	TT07C3Y	5HT4R_HUMAN	Inhibitor	[5]
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Inhibitor	[5]
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Norcisapride Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
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Norcisapride Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Affects Chemical Synthesis	[6]
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Indication(s) of Pomalidomide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[3]
Systemic sclerosis	4A42	Approved	[4]

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	[7]
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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	[8]
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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	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
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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	[11]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Secretion	[12]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Secretion	[12]
Granulocyte colony-stimulating factor (CSF3)	OT9GC6TP	CSF3_HUMAN	Increases Secretion	[12]
Fibroblast growth factor receptor 1 (FGFR1)	OT4GLCXW	FGFR1_HUMAN	Decreases Expression	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[12]
Erythroid transcription factor (GATA1)	OTX1R7O1	GATA1_HUMAN	Decreases Expression	[12]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Expression	[12]
Transcription factor PU.1 (SPI1)	OTVCA1D0	SPI1_HUMAN	Increases Expression	[12]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[12]
Fibroblast growth factor receptor 3 (FGFR3)	OTSAXDIL	FGFR3_HUMAN	Affects Expression	[13]
Endothelial transcription factor GATA-2 (GATA2)	OTBP2QQ2	GATA2_HUMAN	Decreases Expression	[12]
Rhombotin-2 (LMO2)	OTCC370G	RBTN2_HUMAN	Decreases Expression	[12]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Decreases Secretion	[12]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Increases Expression	[12]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[12]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[12]
DNA-binding protein inhibitor ID-2 (ID2)	OT0U1D53	ID2_HUMAN	Increases Expression	[12]
Krueppel-like factor 1 (KLF1)	OT1FK08U	KLF1_HUMAN	Decreases Expression	[12]
CCAAT/enhancer-binding protein epsilon (CEBPE)	OTKZA25M	CEBPE_HUMAN	Increases Expression	[12]
Transcription factor NF-E2 45 kDa subunit (NFE2)	OTLM94BI	NFE2_HUMAN	Decreases Expression	[12]
Zinc finger protein Gfi-1b (GFI1B)	OTRDW8YO	GFI1B_HUMAN	Decreases Expression	[12]
Zinc finger protein Gfi-1 (GFI1)	OT9HB9H8	GFI1_HUMAN	Increases Expression	[12]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[14]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[11]
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Increases Oxidation	[11]
Protein cereblon (CRBN)	OTXH9MDC	CRBN_HUMAN	Increases Response To Substance	[15]
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⏷ Show the Full List of 27 DOT(s)

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	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007174)
3	Pomalidomide 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: 7348).
5	mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83.
6	Cytochrome P450 Involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms. Drug Metab Dispos. 2001 Dec;29(12):1548-54.
7	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
8	DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
9	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.
10	Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
11	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.
12	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.
13	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.
14	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.
15	A Dual Color Immunohistochemistry Assay for Measurement of Cereblon in Multiple Myeloma Patient Samples. Appl Immunohistochem Mol Morphol. 2016 Nov/Dec;24(10):695-702. doi: 10.1097/PAI.0000000000000246.