Details of the Drug Combination

General Information of Drug Combination (ID: DCITIN8)

• Drug Combination Name: Procarbazine + Aliskiren
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Procarbazine (DMIK367): Small molecular drug
  Aliskiren (DM1BV7W): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.8
  Bliss Independence Score: 9.8
  Loewe Additivity Score: 24.67
  LHighest Single Agent (HSA) Score: 24.67

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Procarbazine

Disease Entry	ICD 11	Status	REF
Hodgkin lymphoma	2B30	Approved	[2]

Procarbazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	.	[4]

Procarbazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[5]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[5]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[6]

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	[7]

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	[8]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[9]

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	[10]

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	[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] 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: 7278).
• [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] Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
• [5] In vitro and in vivo evidence for the formation of methyl radical from procarbazine: a spin-trapping study. Carcinogenesis. 1992 May;13(5):799-805.
• [6] Tumour cytochrome P450 and drug activation. Curr Pharm Des. 2002;8(15):1335-47.
• [7] 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.
• [8] Effects of the inhibition of intestinal P-glycoprotein on aliskiren pharmacokinetics in cynomolgus monkeys. Biopharm Drug Dispos. 2015 Jan;36(1):15-33.
• [9] Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren. Br J Clin Pharmacol. 2011 May;71(5):718-26.
• [10] Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31.
• [11] 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.