Details of the Drug Combination

General Information of Drug Combination (ID: DC1DSBV)

• Drug Combination Name: Amonafide + LIAROZOLE
• Indication: Adult acute myeloid leukemia; Status: Investigative [1]
• Component Drugs:
  Amonafide (DMAH59S): Small molecular drug
  LIAROZOLE (DM4OYXE): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HL-60(TB)
  Zero Interaction Potency (ZIP) Score: 4.63
  Bliss Independence Score: 2.94
  Loewe Additivity Score: 3.03
  LHighest Single Agent (HSA) Score: 5.45

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Amonafide

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Prostate cancer	2C82.0	Phase 3	[2]

Indication(s) of LIAROZOLE

Disease Entry	ICD 11	Status	REF
Dermatological disease	DA24.Y	Phase 2/3	[3]

LIAROZOLE Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[4]
Cytochrome P450 26 (CYP26A1)	TTD7Q0R	CP26A_HUMAN	Inhibitor	[5]

LIAROZOLE Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 26A1 (CYP26A1)	OTL1DFWV	CP26A_HUMAN	Decreases Activity	[6]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCWIA14	SW-620	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCM61TA	MOLT-4	Investigative	[1]
Glioma	DCSX2Q5	SF-268	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCSSTEQ	IGROV1	Investigative	[1]
Colon adenocarcinoma	DCDKV2X	COLO 205	Investigative	[7]

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 (NCT00715637) Phase III Randomized Study of Amonafide (AS1413) and Cytarabine Versus Daunorubicin and Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- the ACCEDEStudy. U.S. National Institutes of Health.
• [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: 5210).
• [4] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [5] Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
• [6] Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action. Arch Pharm (Weinheim). 2004 Dec;337(12):687-94. doi: 10.1002/ardp.200400622.
• [7] 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.