Details of the Drug Combination

General Information of Drug Combination (ID: DCSTVG0)

• Drug Combination Name: Cabazitaxel + LIAROZOLE
• Indication: Clear cell renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  LIAROZOLE (DM4OYXE): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: 786-0
  Zero Interaction Potency (ZIP) Score: 7.61
  Bliss Independence Score: 7.33
  Loewe Additivity Score: 5.34
  LHighest Single Agent (HSA) Score: 9.3

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	[5]

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	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[6]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[6]

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	[7]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[7]

Indication(s) of LIAROZOLE

Disease Entry	ICD 11	Status	REF
Dermatological disease	DA24.Y	Phase 2/3	[4]

LIAROZOLE Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[8]
Cytochrome P450 26 (CYP26A1)	TTD7Q0R	CP26A_HUMAN	Inhibitor	[9]

LIAROZOLE Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 26A1 (CYP26A1)	OTL1DFWV	CP26A_HUMAN	Decreases Activity	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DC5M76W	SNB-19	Investigative	[1]
Glioma	DC10VW1	SF-295	Investigative	[1]
Glioma	DCRUFQA	SF-539	Investigative	[1]

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: 5210).
• [5] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [6] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [7] 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.
• [8] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [9] Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
• [10] Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action. Arch Pharm (Weinheim). 2004 Dec;337(12):687-94. doi: 10.1002/ardp.200400622.