Details of the Drug Combination

General Information of Drug Combination (ID: DCQHEB2)

• Drug Combination Name: AS602868 + Prazosin
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  AS602868 (DMKXDOI): Small molecular drug
  Prazosin (DMCD9YG): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 1.493
  Bliss Independence Score: 5.287
  Loewe Additivity Score: 1.657
  LHighest Single Agent (HSA) Score: 1.623

Molecular Interaction Atlas of This Drug Combination

Indication(s) of AS602868

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Discontinued in Phase 1	[2]

AS602868 Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[5]
Nuclear factor NF-kappa-B (NFKB)	TTSXVID	NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN	Inhibitor	[6]
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[5]

AS602868 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[7]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[7]

Indication(s) of Prazosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[3]
Congestive heart failure	BD10	Approved	[3]
Hypertension	BA00-BA04	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]

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	[8]

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	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]

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	[12]

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009941)
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
• [5] Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders. Pharmacol Toxicol. 2001 Feb;88(2):75-80.
• [6] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [7] Pharmacological targeting of NF-kappaB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells. Br J Cancer. 2008 Jan 29;98(2):335-44. doi: 10.1038/sj.bjc.6604082. Epub 2008 Jan 8.
• [8] Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing. Auton Autacoid Pharmacol. 2009 Jul;29(3):117-33.
• [9] 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.
• [10] 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.
• [11] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [12] Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.