Details of the Drug Combination

General Information of Drug Combination (ID: DCCTQBV)

• Drug Combination Name: RTB101 + Prazosin
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  RTB101 (DM62QTW): Small molecular drug
  Prazosin (DMCD9YG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 3.729
  Bliss Independence Score: 4.53
  Loewe Additivity Score: 1.952
  LHighest Single Agent (HSA) Score: 3.475

Molecular Interaction Atlas of This Drug Combination

Indication(s) of RTB101

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

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	[6]

Indication(s) of Prazosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[4]
Congestive heart failure	BD10	Approved	[4]
Hypertension	BA00-BA04	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]

Prazosin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor Alpha-1 (ADRA1)	TTG28O6	NOUNIPROTAC	Antagonist	[7]

Prazosin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]

Prazosin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[11]

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] ClinicalTrials.gov (NCT04139915) Effect of RTB101 on Illness Associated With Respiratory Tract Infections in the Elderly. U.S. National Institutes of Health.
• [3] 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.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
• [6] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [7] Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing. Auton Autacoid Pharmacol. 2009 Jul;29(3):117-33.
• [8] Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10594-9.
• [9] P-glycoprotein and breast cancer resistance protein expression and function at the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in streptozotocin-induced diabetes in rats. Brain Res. 2011 Jan 25;1370:238-45.
• [10] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [11] Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.