Details of the Drug Combination

General Information of Drug Combination (ID: DC50TGP)

Drug Combination Name

Tucatinib Capecitabine

Indication

Disease Entry	Status	REF
Breast Cancer	Phase 2	[1]

Component Drugs

Tucatinib DMBESUA

Capecitabine DMTS85L

N.A.

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Tucatinib

Disease Entry	ICD 11	Status	REF
HER2-positive breast cancer	2C60-2C65	Approved	[2]
Gastric adenocarcinoma	2B72	Phase 2/3	[3]

Tucatinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[2]
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Indication(s) of Capecitabine

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[4]
Colon adenocarcinoma	N.A.	Approved	[4]
Colorectal cancer	2B91.Z	Approved	[5]
Metastasis from malignant tumor of colon	N.A.	Approved	[4]
Rectal adenocarcinoma	2B92	Approved	[4]
Breast cancer	2C60-2C65	Phase 3	[5]
Colon cancer	2B90.Z	Investigative	[4]
Gastric cancer	2B72	Investigative	[4]

Capecitabine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[9]
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Capecitabine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytidine aminohydrolase (CDA)	DEKEDRC	CDD_HUMAN	Metabolism	[10]
Thymidine phosphorylase (TYMP)	DE4HCYL	TYPH_HUMAN	Metabolism	[11]
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Capecitabine Interacts with 65 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydropyrimidine dehydrogenase (DPYD)	OTWRF2NR	DPYD_HUMAN	Increases Expression	[12]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[13]
C-C motif chemokine 21 (CCL21)	OT7DOXEM	CCL21_HUMAN	Decreases Expression	[7]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Decreases Expression	[7]
Aquaporin-8 (AQP8)	OT99JKME	AQP8_HUMAN	Increases Expression	[7]
Complement C3 (C3)	OTCH5GS0	CO3_HUMAN	Decreases Expression	[7]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Decreases Expression	[7]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Secretion	[14]
B-lymphocyte antigen CD20 (MS4A1)	OTZTVUBX	CD20_HUMAN	Decreases Expression	[7]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1)	OTGP6GA4	NR4A1_HUMAN	Decreases Expression	[7]
40-kDa huntingtin-associated protein (F8A1)	OTXTQ59R	HAP40_HUMAN	Decreases Expression	[7]
Chloride anion exchanger (SLC26A3)	OTBNK2U2	S26A3_HUMAN	Increases Expression	[7]
Nuclear receptor subfamily 4 group A member 2 (NR4A2)	OT3F9IR2	NR4A2_HUMAN	Decreases Expression	[7]
Potassium-transporting ATPase alpha chain 2 (ATP12A)	OTSQSKEK	AT12A_HUMAN	Increases Expression	[7]
Serine/threonine-protein kinase SIK1 (SIK1)	OT6FCHME	SIK1_HUMAN	Decreases Expression	[7]
Hemoglobin subunit beta (HBB)	OT514IKQ	HBB_HUMAN	Decreases Expression	[7]
Hemoglobin subunit alpha (HBA1)	OTW2BQF4	HBA_HUMAN	Decreases Expression	[7]
Paired box protein Pax-5 (PAX5)	OTYBJJWX	PAX5_HUMAN	Decreases Expression	[7]
Endoplasmic reticulum aminopeptidase 2 (ERAP2)	OTEMENYF	ERAP2_HUMAN	Decreases Expression	[7]
Fc receptor-like A (FCRLA)	OT6MK4M1	FCRLA_HUMAN	Decreases Expression	[7]
Leucine-rich repeat-containing protein 15 (LRRC15)	OTX7JL8H	LRC15_HUMAN	Decreases Expression	[7]
C-C motif chemokine 19 (CCL19)	OTQ2UJMH	CCL19_HUMAN	Decreases Expression	[7]
E3 ubiquitin-protein ligase TRIM31 (TRIM31)	OT7VW6RP	TRI31_HUMAN	Increases Expression	[7]
Interleukin-1 receptor type 2 (IL1R2)	OT0G7E35	IL1R2_HUMAN	Increases Response To Substance	[8]
Interleukin-17 receptor B (IL17RB)	OT0KDNSF	I17RB_HUMAN	Increases Response To Substance	[8]
Glycogen phosphorylase, brain form (PYGB)	OT2ZTJT0	PYGB_HUMAN	Increases Response To Substance	[8]
Calcium and integrin-binding protein 1 (CIB1)	OT4BVCRU	CIB1_HUMAN	Increases Response To Substance	[8]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)	OT5I4Y9K	PLCB_HUMAN	Increases Response To Substance	[8]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	OT6RMDCE	KAPCB_HUMAN	Decreases Response To Substance	[8]
Claudin-3 (CLDN3)	OT71MN9S	CLD3_HUMAN	Increases Response To Substance	[8]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Decreases Response To Substance	[8]
Protein flightless-1 homolog (FLII)	OT7G9JG6	FLII_HUMAN	Decreases Response To Substance	[8]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Decreases Response To Substance	[8]
Ras-related protein R-Ras2 (RRAS2)	OT83NCEB	RRAS2_HUMAN	Decreases Response To Substance	[8]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Response To Substance	[8]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Increases Response To Substance	[15]
Ras-related protein Rab-40B (RAB40B)	OTCA9ZF5	RB40B_HUMAN	Increases Response To Substance	[8]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Increases Response To Substance	[8]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7)	OTDNTHNR	ABCB7_HUMAN	Decreases Response To Substance	[8]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13)	OTESFZSO	PTN13_HUMAN	Decreases Response To Substance	[8]
ADP-ribosylation factor-like protein 4D (ARL4D)	OTG5I3KU	ARL4D_HUMAN	Decreases Response To Substance	[8]
Double-strand break repair protein MRE11 (MRE11)	OTGU8TZM	MRE11_HUMAN	Decreases Response To Substance	[8]
Inorganic pyrophosphatase (PPA1)	OTHZK1QB	IPYR_HUMAN	Increases Response To Substance	[8]
Polycystin-2 (PKD2)	OTIXBU8H	PKD2_HUMAN	Decreases Response To Substance	[8]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[8]
Transcriptional activator Myb (MYB)	OTJH64IV	MYB_HUMAN	Increases Response To Substance	[8]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1)	OTJISZOX	PLCE1_HUMAN	Increases Response To Substance	[8]
Plakophilin-2 (PKP2)	OTJOVF68	PKP2_HUMAN	Increases Response To Substance	[8]
Transcriptional enhancer factor TEF-1 (TEAD1)	OTK6971C	TEAD1_HUMAN	Decreases Response To Substance	[8]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Response To Substance	[8]
Myelin regulatory factor (MYRF)	OTKF6AEB	MYRF_HUMAN	Increases Response To Substance	[8]
Galectin-4 (LGALS4)	OTKQCG0H	LEG4_HUMAN	Increases Response To Substance	[8]
Four and a half LIM domains protein 1 (FHL1)	OTN535SU	FHL1_HUMAN	Decreases Response To Substance	[8]
Hepatoma-derived growth factor-related protein 3 (HDGFL3)	OTNN7WYH	HDGR3_HUMAN	Decreases Response To Substance	[8]
E3 ubiquitin-protein ligase TRIM15 (TRIM15)	OTNYAKP6	TRI15_HUMAN	Increases Response To Substance	[8]
Dermatan-sulfate epimerase (DSE)	OTQ108VJ	DSE_HUMAN	Decreases Response To Substance	[8]
Anterior gradient protein 2 homolog (AGR2)	OTRRZT7W	AGR2_HUMAN	Increases Response To Substance	[8]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Increases Response To Substance	[8]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Decreases Response To Substance	[8]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Response To Substance	[8]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1)	OTVKRET0	THIK_HUMAN	Increases Response To Substance	[8]
Tissue alpha-L-fucosidase (FUCA1)	OTW71IK4	FUCO_HUMAN	Increases Response To Substance	[8]
GTPase HRas (HRAS)	OTWQN0DP	RASH_HUMAN	Decreases Response To Substance	[8]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Increases Response To Substance	[8]
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⏷ Show the Full List of 65 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
HER2 Positive Metastatic Breast Cancers	DC46KGK	N. A.	Phase 1	[16]
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References

1	ClinicalTrials.gov (NCT04721977) A Study of Tucatinib (MK-7119) in Combination With Trastuzumab and Capecitabine in Participants With Previously Treated Locally Advanced Unresectable or Metastatic Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Carcinoma (MK-7119-001)
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
3	ClinicalTrials.gov (NCT04499924) Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer (MOUNTAINEER-02). U.S. National Institutes of Health.
4	Capecitabine 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: 6799).
6	Drug-drug interaction potentials of tucatinib inhibition of human UDP-glucuronosyltransferases. Chem Biol Interact. 2023 Aug 25;381:110574. doi: 10.1016/j.cbi.2023.110574. Epub 2023 May 30.
7	Gene expression responses reflecting 5-FU-induced toxicity: Comparison between patient colon tissue and 3D human colon organoids. Toxicol Lett. 2022 Dec 1;371:17-24. doi: 10.1016/j.toxlet.2022.09.013. Epub 2022 Sep 29.
8	Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
9	UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.
10	Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889. Int J Cancer. 2003 Sep 20;106(5):799-805.
11	Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther. 2002 Oct;1(12):1139-45.
12	DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. Int J Oncol. 2007 Aug;31(2):413-8.
13	Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. Biomed Pharmacother. 2007 Oct;61(9):596-600.
14	P38 MAPK, NF-B, and JAK-STAT3 Signaling Pathways Involved in Capecitabine-Induced Hand-Foot Syndrome via Interleukin 6 or Interleukin 8 Abnormal Expression. Chem Res Toxicol. 2022 Mar 21;35(3):422-430. doi: 10.1021/acs.chemrestox.1c00317. Epub 2022 Feb 11.
15	A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Curr Drug Metab. 2008 May;9(4):336-43. doi: 10.2174/138920008784220646.
16	ClinicalTrials.gov (NCT02025192) A Study of Tucatinib (ONT-380) Combined With Capecitabine and/or Trastuzumab in Patients With HER2+ Metastatic Breast Cancer