Details of the Drug Combination

General Information of Drug Combination (ID: DCZCDJO)

• Drug Combination Name: Estramustine + Erlotinib
• Indication: Ewing sarcoma-peripheral primitive neuroectodermal tumour; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  Erlotinib (DMCMBHA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ES2
  Zero Interaction Potency (ZIP) Score: 17.43
  Bliss Independence Score: 6.98
  Loewe Additivity Score: 17.58
  LHighest Single Agent (HSA) Score: 5.16

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Estramustine

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

Estramustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estramustine binding protein (EMBP)	TTSBFYK	NOUNIPROTAC	Binder	[5]

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	[6]

Estramustine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[7]

Indication(s) of Erlotinib

Disease Entry	ICD 11	Status	REF
Adrenal gland neoplasm	N.A.	Approved	[3]
Adult hepatocellular carcinoma	N.A.	Approved	[3]
Brain cancer	2A00	Approved	[3]
Esophageal disorder	N.A.	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Pancreatic adenocarcinoma	N.A.	Approved	[3]
Psoriasis	EA90	Approved	[3]
Salivary gland squamous cell carcinoma	N.A.	Approved	[3]
Pancreatic cancer	2C10	Phase 3	[4]
Colon cancer	2B90.Z	Phase 2	[4]
Ependymoma	2A00.0Y	Investigative	[3]
Neoplastic meningitis	N.A.	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]

Erlotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[8]

Erlotinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

Erlotinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCL87OK	UWB1289+BRCA1	Investigative	[13]
Breast carcinoma	DCSDGM8	OCUBM	Investigative	[13]
Carcinoma	DC84A3A	EFM192B	Investigative	[13]
Colon adenocarcinoma	DCUCEBZ	LOVO	Investigative	[13]
Colon carcinoma	DC1XT6A	RKO	Investigative	[13]
Invasive ductal carcinoma	DC07Z8U	T-47D	Investigative	[13]
Adenocarcinoma	DC09RVN	OVCAR3	Investigative	[14]
Adenocarcinoma	DCNUD6B	NCIH2122	Investigative	[14]
Adenocarcinoma	DCTVHIA	COLO320DM	Investigative	[14]
Adenocarcinoma	DCAODRI	HT29	Investigative	[14]
Adenocarcinoma	DC0WVH4	SW-620	Investigative	[14]
Amelanotic melanoma	DC0TU8K	A2058	Investigative	[14]
Large cell lung carcinoma	DCFSS8I	NCI-H460	Investigative	[14]
Malignant melanoma	DCRGM44	A375	Investigative	[14]
Malignant melanoma	DC2PCL9	HT144	Investigative	[14]
Malignant melanoma	DCN2962	RPMI7951	Investigative	[14]
Malignant melanoma	DC1EM91	UACC62	Investigative	[14]
Mesothelioma	DCVS3W2	MSTO	Investigative	[14]
Non small cell carcinoma	DCXJB7E	SKMES1	Investigative	[14]
Ovarian endometrioid adenocarcinoma	DCKQ987	A2780	Investigative	[14]
Ovarian serous cystadenocarcinoma	DCI0N3D	SK-OV-3	Investigative	[14]
Prostate carcinoma	DCMGXD5	LNCAP	Investigative	[14]
Prostate carcinoma	DC7HOPS	VCAP	Investigative	[14]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Erlotinib 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: 4920).
• [5] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [6] 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.
• [7] 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.
• [8] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [9] Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
• [10] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
• [11] In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
• [12] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [13] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [14] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976