Details of the Drug Combination

General Information of Drug Combination (ID: DC6DV3I)

• Drug Combination Name: Cabazitaxel + Estramustine
• Indication: Astrocytoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Estramustine (DMWTAOI): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: U251
  Zero Interaction Potency (ZIP) Score: 4.65
  Bliss Independence Score: 3.7
  Loewe Additivity Score: 6.44
  LHighest Single Agent (HSA) Score: 9

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 Estramustine

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[4]

Estramustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estramustine binding protein (EMBP)	TTSBFYK	NOUNIPROTAC	Binder	[8]

Estramustine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Estramustine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC1AXBJ	DU-145	Investigative	[1]
Adenocarcinoma	DCBAZBE	A549	Investigative	[1]
Adenocarcinoma	DC4EB3E	HT29	Investigative	[1]
Adenocarcinoma	DC4IPS9	HCT116	Investigative	[1]
Adenocarcinoma	DCCZXCR	HCT-15	Investigative	[1]
Adenocarcinoma	DC3YZ3T	HCC-2998	Investigative	[1]
Adult acute myeloid leukemia	DC86NJ2	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCUT1KH	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DCF9765	SR	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCNZNXL	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DCO913O	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCW4JX3	786-0	Investigative	[1]
Cutaneous melanoma	DCVKE8S	SK-MEL-5	Investigative	[1]
Glioma	DCQBVFJ	SF-539	Investigative	[1]
Glioma	DCNP2JC	SF-295	Investigative	[1]
Large cell lung carcinoma	DCWAMGC	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCWDWAO	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCCETUR	NCI-H522	Investigative	[1]
Malignant melanoma	DCW7XPF	UACC62	Investigative	[1]
Melanoma	DCPSGGQ	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCU9C20	NCI-H322M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCS45O5	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCLL8BU	ACHN	Investigative	[1]
Plasma cell myeloma	DC3VZHC	RPMI-8226	Investigative	[1]
Prostate carcinoma	DCQWLDO	PC-3	Investigative	[1]
Renal cell carcinoma	DCXY7M1	SN12C	Investigative	[1]
Breast adenocarcinoma	DCX5ASX	MDA-MB-468	Investigative	[12]
Carcinoma	DC1STTG	RXF 393	Investigative	[12]
Carcinoma	DCJJYTI	MCF7	Investigative	[12]
Invasive ductal carcinoma	DCSP3TQ	HS 578T	Investigative	[12]
Invasive ductal carcinoma	DC2BD07	BT-549	Investigative	[12]
Invasive ductal carcinoma	DCB8VWC	T-47D	Investigative	[12]

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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [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] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [9] Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.
• [10] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [11] Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. J Neurooncol. 2001 Aug;54(1):23-9. doi: 10.1023/a:1012566601485.
• [12] 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.