Details of the Drug Combination

General Information of Drug Combination (ID: DCBSY8M)

• Drug Combination Name: BRL-15572 + Aliskiren
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  BRL-15572 (DMM61Y2): Small molecular drug
  Aliskiren (DM1BV7W): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 10.58
  Bliss Independence Score: 10.58
  Loewe Additivity Score: 27.02
  LHighest Single Agent (HSA) Score: 27.03

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BRL-15572

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[2]

BRL-15572 Interacts with 9 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1B receptor (HTR1B)	TTK8CXU	5HT1B_HUMAN	Agonist	[4]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Agonist	[4]
5-HT 6 receptor (HTR6)	TTJS8PY	5HT6R_HUMAN	Agonist	[4]
5-HT 2B receptor (HTR2B)	TT0K1SC	5HT2B_HUMAN	Agonist	[4]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Agonist	[4]
5-HT 1F receptor (HTR1F)	TT0MI3F	5HT1F_HUMAN	Agonist	[4]
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[4]
5-HT 2C receptor (HTR2C)	TTWJBZ5	5HT2C_HUMAN	Agonist	[4]
5-HT 1E receptor (HTR1E)	TTCPG9S	5HT1E_HUMAN	Agonist	[4]

Indication(s) of Aliskiren

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[3]

Aliskiren Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensinogenase renin (REN)	TTB2MXP	RENI_HUMAN	Inhibitor	[5]

Aliskiren Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[7]

Aliskiren Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Aliskiren Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[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] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 10).
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4812).
• [4] SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
• [5] Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patie... J Renin Angiotensin Aldosterone Syst. 2009 Sep;10(3):157-67.
• [6] Effects of the inhibition of intestinal P-glycoprotein on aliskiren pharmacokinetics in cynomolgus monkeys. Biopharm Drug Dispos. 2015 Jan;36(1):15-33.
• [7] Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren. Br J Clin Pharmacol. 2011 May;71(5):718-26.
• [8] Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31.
• [9] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.