Details of the Drug Combination

General Information of Drug Combination (ID: DCVWAVK)

• Drug Combination Name: Estramustine + RTB101
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  RTB101 (DM62QTW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCIH520
  Zero Interaction Potency (ZIP) Score: 7.32
  Bliss Independence Score: 7.86
  Loewe Additivity Score: 6.86
  LHighest Single Agent (HSA) Score: 10.67

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 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	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[8]

Indication(s) of RTB101

Disease Entry	ICD 11	Status	REF
Respiratory tract infection	CA45	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

RTB101 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
CREB-regulated transcription coactivator 1 (TORC1)	TT4GO0F	CRTC1_HUMAN	Inhibitor	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCV8NO5	ES2	Investigative	[10]
Breast and ovarian cancer syndrome	DC4XUI4	UWB1289	Investigative	[11]
Breast and ovarian cancer syndrome	DC3GT33	UWB1289+BRCA1	Investigative	[11]
Breast carcinoma	DCNYEZ5	OCUBM	Investigative	[11]
Carcinoma	DC29LSD	OV90	Investigative	[11]
Carcinoma	DCFL1OS	EFM192B	Investigative	[11]
Colon adenocarcinoma	DCNC4GN	LOVO	Investigative	[11]
Invasive ductal carcinoma	DC3CRWQ	T-47D	Investigative	[11]
Adenocarcinoma	DCMD25L	CAOV3	Investigative	[1]
Adenocarcinoma	DC570BS	A427	Investigative	[1]
Adenocarcinoma	DCZS4BT	NCIH2122	Investigative	[1]
Adenocarcinoma	DCBUFC7	NCIH23	Investigative	[1]
Adenocarcinoma	DCVH6SS	DLD1	Investigative	[1]
Adenocarcinoma	DC0T7S2	HT29	Investigative	[1]
Adenocarcinoma	DC9S79Y	SW-620	Investigative	[1]
Amelanotic melanoma	DCQ7QFU	A2058	Investigative	[1]
Germ cell tumour	DCZYUWT	PA1	Investigative	[1]
Large cell lung carcinoma	DCSWDPY	NCI-H460	Investigative	[1]
Malignant melanoma	DCSDG9F	A375	Investigative	[1]
Malignant melanoma	DCSC9W4	HT144	Investigative	[1]
Malignant melanoma	DCAIK3M	RPMI7951	Investigative	[1]
Malignant melanoma	DCK7ZE1	SKMEL30	Investigative	[1]
Mesothelioma	DC1SDJJ	MSTO	Investigative	[1]
Non small cell carcinoma	DC862TP	SKMES1	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DC8ZEIC	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC8BFJC	SK-OV-3	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] ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [4] ClinicalTrials.gov (NCT04409327) Phase 2 Study to Determine if RTB101 Reduces the Severity of COVID-19 in Older Adults Residing in Nursing Homes. U.S. National Institutes of Health.
• [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] 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.
• [9] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [10] 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.
• [11] 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.