Details of the Drug Combination

General Information of Drug Combination (ID: DCGJNWU)

• Drug Combination Name: Indazole derivative 5 + Estramustine
• Indication: Large cell lung carcinoma; Status: Investigative [1]
• Component Drugs:
  Indazole derivative 5 (DMM1I8R): Small molecular drug
  Estramustine (DMWTAOI): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCI-H460
  Zero Interaction Potency (ZIP) Score: 4.16
  Bliss Independence Score: 6.07
  Loewe Additivity Score: 5.41
  LHighest Single Agent (HSA) Score: 6.79

Molecular Interaction Atlas of This Drug Combination

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[3]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[3]

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	[4]

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	[5]

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	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[7]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCLC8BF	HL-60(TB)	Investigative	[8]
Adult T acute lymphoblastic leukemia	DCXG41K	MOLT-4	Investigative	[8]
Anaplastic large cell lymphoma	DCQPS6B	SR	Investigative	[8]
Astrocytoma	DCNZ6EV	U251	Investigative	[8]
Clear cell renal cell carcinoma	DCZUDJK	786-0	Investigative	[8]
Glioma	DCT80CT	SF-268	Investigative	[8]
Papillary renal cell carcinoma	DC1CSVY	ACHN	Investigative	[8]
Plasma cell myeloma	DC3F4SC	RPMI-8226	Investigative	[8]
Renal cell carcinoma	DCV001L	UO-31	Investigative	[8]
Carcinoma	DCHB54N	RXF 393	Investigative	[9]
Invasive ductal carcinoma	DC6YA5I	T-47D	Investigative	[9]
Adenocarcinoma	DCW0NXL	DU-145	Investigative	[1]
Adenocarcinoma	DCGPPVP	NCIH23	Investigative	[1]
Amelanotic melanoma	DC2W91P	MDA-MB-435	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC53RD4	OVCAR-8	Investigative	[1]
Lung adenocarcinoma	DCK45JK	HOP-62	Investigative	[1]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [4] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.