Details of the Drug Combination

General Information of Drug Combination (ID: DCT83ME)

• Drug Combination Name: Cabazitaxel + Bleomycin
• Indication: Carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Bleomycin (DMNER5S): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RXF 393
  Zero Interaction Potency (ZIP) Score: 8.49
  Bliss Independence Score: 11.59
  Loewe Additivity Score: 9
  LHighest Single Agent (HSA) Score: 14.09

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

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

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[6]

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	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]

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	[8]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[8]

Indication(s) of Bleomycin

Disease Entry	ICD 11	Status	REF
Cervical cancer	2C77.0	Approved	[4]
Head and neck cancer	2D42	Approved	[4]
Hodgkin lymphoma	2B30	Approved	[5]
Penile cancer	N.A.	Approved	[4]
Testicular germ cell tumor	N.A.	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]
Follicular lymphoma	2A80	Investigative	[4]

Bleomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[13]

Bleomycin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Bleomycin hydrolase (BLMH)	DECH1VP	BLMH_HUMAN	Metabolism	[14]

Bleomycin Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bleomycin hydrolase (BLMH)	OT2QPWQJ	BLMH_HUMAN	Affects Response To Substance	[15]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[16]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Expression	[16]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[16]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Increases Expression	[17]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Expression	[17]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[17]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Increases Expression	[17]
Mucin-5AC (MUC5AC)	OTJV8O04	MUC5A_HUMAN	Increases Expression	[17]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Increases Expression	[17]
Transmembrane protein 250 (TMEM250)	OTLJ4G5G	TM250_HUMAN	Increases Expression	[9]
Suppressor of cytokine signaling 1 (SOCS1)	OTWA9KFU	SOCS1_HUMAN	Decreases Expression	[18]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[19]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[10]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[20]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[10]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[21]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[10]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[22]
Cathepsin S (CTSS)	OT3PXIPM	CATS_HUMAN	Increases Expression	[23]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[24]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Decreases Expression	[9]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Increases Expression	[10]
Unconventional myosin-Ie (MYO1E)	OTM9YSIZ	MYO1E_HUMAN	Decreases Expression	[9]
Transcription intermediary factor 1-beta (TRIM28)	OTE38OBF	TIF1B_HUMAN	Increases Phosphorylation	[19]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[19]
Structural maintenance of chromosomes protein 1A (SMC1A)	OT9ZMRK9	SMC1A_HUMAN	Increases Phosphorylation	[19]
7SK snRNA methylphosphate capping enzyme (MEPCE)	OTRBQEYP	MEPCE_HUMAN	Increases Expression	[9]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[9]
Terminal nucleotidyltransferase 4B (TENT4B)	OTUF6FWW	PAPD5_HUMAN	Decreases Expression	[9]
Lipase member H (LIPH)	OTRGYLKL	LIPH_HUMAN	Decreases Expression	[9]
Abasic site processing protein HMCES (HMCES)	OTVRDL6U	HMCES_HUMAN	Decreases Expression	[9]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[9]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[9]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)	OT9I1XUO	CEIP2_HUMAN	Decreases Expression	[9]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Decreases Expression	[9]
Transmembrane and coiled-coil domain protein 3 (TMCC3)	OTAIQ6V6	TMCC3_HUMAN	Decreases Expression	[9]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)	OT27CCUF	SIAT9_HUMAN	Decreases Expression	[9]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[25]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Affects Response To Substance	[26]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC2EBHQ	A549	Investigative	[27]
Adenocarcinoma	DCNY6UL	HCT116	Investigative	[27]
Adenocarcinoma	DC0AXJX	HCT-15	Investigative	[27]
Adult acute myeloid leukemia	DCK0ODQ	HL-60(TB)	Investigative	[27]
Adult T acute lymphoblastic leukemia	DCC69VH	MOLT-4	Investigative	[27]
Anaplastic large cell lymphoma	DC440A8	SR	Investigative	[27]
Astrocytoma	DC5ZSOA	SNB-19	Investigative	[27]
Clear cell renal cell carcinoma	DCNWSRB	786-0	Investigative	[27]
Clear cell renal cell carcinoma	DCR346H	A498	Investigative	[27]
Glioblastoma	DC80NU3	SNB-75	Investigative	[27]
High grade ovarian serous adenocarcinoma	DCGWP4Q	OVCAR-8	Investigative	[27]
Large cell lung carcinoma	DCIG22T	NCI-H460	Investigative	[27]
Lung adenocarcinoma	DCHWI12	HOP-62	Investigative	[27]
Lung adenocarcinoma	DCDVSR9	NCI-H522	Investigative	[27]
Melanoma	DCXZSMZ	UACC-257	Investigative	[27]
Ovarian serous cystadenocarcinoma	DCYQKZV	SK-OV-3	Investigative	[27]
Renal cell carcinoma	DCVMNBG	UO-31	Investigative	[27]
Renal cell carcinoma	DC3G0K1	SN12C	Investigative	[27]
Breast adenocarcinoma	DCI2YV5	MDA-MB-468	Investigative	[1]
Invasive ductal carcinoma	DCXLQQP	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCX7OK8	BT-549	Investigative	[1]
Invasive ductal carcinoma	DC1H7AD	T-47D	Investigative	[1]

References

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• [3] Cabazitaxel FDA Label
• [4] Bleomycin FDA Label
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• [8] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
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• [12] XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole. Environ Health Perspect. 2010 Dec;118(12):1707-13. doi: 10.1289/ehp.1002312. Epub 2010 Aug 11.
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• [14] The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage. Mutat Res. 1998 Oct 12;421(1):1-7.
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• [21] Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways. Chem Biol Interact. 2016 Mar 5;247:1-10. doi: 10.1016/j.cbi.2016.01.012. Epub 2016 Jan 29.
• [22] Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. Biochem Pharmacol. 2014 Oct 1;91(3):312-22. doi: 10.1016/j.bcp.2014.08.006. Epub 2014 Aug 15.
• [23] Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009 Apr 15;124(8):1794-801. doi: 10.1002/ijc.24095.
• [24] Bleomycin-induced nuclear factor-kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta. Toxicol Lett. 2009 Jun 22;187(3):194-200. doi: 10.1016/j.toxlet.2009.02.023. Epub 2009 Mar 13.
• [25] Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
• [26] DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.
• [27] 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.