Details of the Drug Combination

General Information of Drug Combination (ID: DCY0QWA)

• Drug Combination Name: Estramustine + Aminolevulinic Acid Hydrochloride
• Indication: Anaplastic large cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  Aminolevulinic Acid Hydrochloride (DMWNHPC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SR
  Zero Interaction Potency (ZIP) Score: 3.29
  Bliss Independence Score: 2.7
  Loewe Additivity Score: 1.88
  LHighest Single Agent (HSA) Score: 4.17

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	[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]

Indication(s) of Aminolevulinic Acid Hydrochloride

Disease Entry	ICD 11	Status	REF
Actinic keratosis	EK90.0	Approved	[3]

Aminolevulinic Acid Hydrochloride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Protoporphyrinogen oxidase (PPOX)	TTNFMS9	PPOX_HUMAN	Modulator	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCZL1ZQ	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCA8GKF	MOLT-4	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCNVSHS	CCRF-CEM	Investigative	[1]
Renal cell carcinoma	DCFRIED	SN12C	Investigative	[1]
Adenocarcinoma	DCAG39G	OVCAR3	Investigative	[9]
Adenocarcinoma	DCNDLEH	A549	Investigative	[9]
Large cell lung carcinoma	DCIZBFU	NCI-H460	Investigative	[9]
Malignant melanoma	DCXDHZW	LOX IMVI	Investigative	[9]

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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] 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.