Details of the Drug Combination

General Information of Drug Combination (ID: DCA2Y1M)

• Drug Combination Name: Cabazitaxel + Uracil mustard
• Indication: Clear cell renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Uracil mustard (DMHL7OB): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TK-10
  Zero Interaction Potency (ZIP) Score: 3.68
  Bliss Independence Score: 3.89
  Loewe Additivity Score: 4.12
  LHighest Single Agent (HSA) Score: 7.36

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 Uracil mustard

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[4]
Chronic myelogenous leukaemia	2A20.0	Approved	[5]
Polycythemia vera	2A20.4	Approved	[5]
Small lymphocytic lymphoma	2A82.0	Approved	[5]

Uracil mustard Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[9]

Uracil mustard Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1)	OT7FBG5W	NAR1_HUMAN	Increases ADR	[10]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases ADR	[10]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases ADR	[10]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[10]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC92Z5J	A549	Investigative	[1]
Adenocarcinoma	DCFR5BZ	HCT116	Investigative	[1]
Adenocarcinoma	DCR3D0Y	HCT-15	Investigative	[1]
Adult acute myeloid leukemia	DCFN6DO	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DC9I1D2	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCOGUGZ	SR	Investigative	[1]
Astrocytoma	DCHD984	SNB-19	Investigative	[1]
Clear cell renal cell carcinoma	DC0IYWJ	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCZX6JK	786-0	Investigative	[1]
Cutaneous melanoma	DCU2BY5	SK-MEL-28	Investigative	[1]
Glioblastoma	DCJG7W0	SNB-75	Investigative	[1]
Glioma	DCB031S	SF-295	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC4Q36A	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DCD68U0	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC6WSFQ	HOP-62	Investigative	[1]
Lung adenocarcinoma	DC4UFKO	EKVX	Investigative	[1]
Lung adenocarcinoma	DCK73HK	MDA-MB-231	Investigative	[1]
Melanoma	DCA3GKP	SK-MEL-2	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCDTEVZ	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCG5LSJ	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DCSDUI4	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCRR3BY	SK-OV-3	Investigative	[1]
Prostate carcinoma	DC8MI7J	PC-3	Investigative	[1]
Renal cell carcinoma	DCMUCUX	SN12C	Investigative	[1]
Breast adenocarcinoma	DCSQJ6O	MDA-MB-468	Investigative	[11]
Carcinoma	DCHZFH1	RXF 393	Investigative	[11]
Carcinoma	DCKVE2U	MCF7	Investigative	[11]
Colon carcinoma	DCY22JJ	KM12	Investigative	[11]
Invasive ductal carcinoma	DC49E4L	BT-549	Investigative	[11]

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] 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: 6798).
• [3] Cabazitaxel 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: 7621).
• [5] Uracil mustard FDA Label
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [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.
• [9] Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
• [10] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [11] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.