Details of the Drug Combination

General Information of Drug Combination (ID: DCWH56J)

• Drug Combination Name: Epirubicin + Cabazitaxel
• Indication: Papillary renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Cabazitaxel (DMPAZHC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ACHN
  Zero Interaction Potency (ZIP) Score: 10.57
  Bliss Independence Score: 9.87
  Loewe Additivity Score: 6.83
  LHighest Single Agent (HSA) Score: 12.54

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Epirubicin

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[2]

Epirubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[5]

Epirubicin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[6]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]

Epirubicin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[8]

Epirubicin Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[9]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[9]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[9]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[10]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[12]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[13]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[14]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Mutagenesis	[15]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Increases Phosphorylation	[16]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[16]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[17]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[12]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[12]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Increases Phosphorylation	[16]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[17]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[18]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[19]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[18]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[20]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[21]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[22]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[23]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[24]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[25]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[18]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[20]

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
Metastatic prostate carcinoma	N.A.	Investigative	[4]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[26]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[27]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[27]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[27]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[28]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[28]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Clear cell renal cell carcinoma	DC5YBE5	CAKI-1	Investigative	[1]
Adenocarcinoma	DCLBW0L	NCIH23	Investigative	[29]
High grade ovarian serous adenocarcinoma	DCRXC65	OVCAR-8	Investigative	[29]
Lung adenocarcinoma	DCT4R29	MDA-MB-231	Investigative	[29]
Lung adenocarcinoma	DC4TLNV	HOP-62	Investigative	[29]
Melanoma	DC2JSC2	MALME-3M	Investigative	[29]
Pleural epithelioid mesothelioma	DC1CZNP	NCI-H226	Investigative	[29]

References

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• [19] MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
• [20] Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
• [21] [Knock-down of apollon gene by antisense oligodeoxynucleotide inhibits the proliferation of Lovo cells and enhances chemo-sensitivity]. Yao Xue Xue Bao. 2011 Feb;46(2):138-45.
• [22] [Antisense oligonucleotide targeting survivin induces apoptosis of renal clear-cell carcinoma cells and enhances their sensitivity to epirubicin in vitro]. Zhonghua Zhong Liu Za Zhi. 2005 Aug;27(8):468-70.
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