Details of the Drug Combination

General Information of Drug Combination (ID: DCIF4IT)

• Drug Combination Name: TRICIRIBINE + Cotellic
• Indication: Embryonal rhabdomyosarcoma; Status: Investigative [1]
• Component Drugs:
  TRICIRIBINE (DM8IC5H): Small molecular drug
  Cotellic (DMF9M57): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RD
  Zero Interaction Potency (ZIP) Score: 19.672
  Bliss Independence Score: 19.073
  Loewe Additivity Score: 9.03
  LHighest Single Agent (HSA) Score: 11.274

Molecular Interaction Atlas of This Drug Combination

Indication(s) of TRICIRIBINE

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]

TRICIRIBINE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[6]

TRICIRIBINE Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Adenosine kinase (ADK)	DE7T5VX	ADK_HUMAN	Metabolism	[7]

TRICIRIBINE Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Activity	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Expression	[9]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[9]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[10]
RAC-beta serine/threonine-protein kinase (AKT2)	OTBB632K	AKT2_HUMAN	Decreases Phosphorylation	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[9]

Indication(s) of Cotellic

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Phase 3	[3]
Breast cancer	2C60-2C65	Phase 2	[4]
Head and neck cancer	2D42	Phase 1	[4]
Renal cell carcinoma	2C90	Phase 1	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
Urothelial carcinoma	2C92.0	Phase 1	[4]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Embryonal rhabdomyosarcoma	DC3DVEO	Rh36	Investigative	[1]
Embryonal rhabdomyosarcoma	DCPHXGK	CTR	Investigative	[1]

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: 5920).
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT01106599) A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0623 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
• [6] Design, synthesis and antiviral activity of novel 4,5-disubstituted 7-(beta-D-ribofuranosyl)pyrrolo[2,3-d][1,2,3]triazines and the novel 3-amino-5-... J Med Chem. 2005 Jun 2;48(11):3840-51.
• [7] Phosphorylation of triciribine is necessary for activity against HIV type 1. AIDS Res Hum Retroviruses. 1998 Oct 10;14(15):1315-22.
• [8] Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis. Endocrinology. 2013 Feb;154(2):956-67. doi: 10.1210/en.2012-1836. Epub 2012 Dec 18.
• [9] Metformin and epothilone A treatment up regulate pro-apoptotic PARP-1, Casp-3 and H2AX genes and decrease of AKT kinase level to control cell death of human hepatocellular carcinoma and ovary adenocarcinoma cells. Toxicol In Vitro. 2018 Mar;47:48-62. doi: 10.1016/j.tiv.2017.11.001. Epub 2017 Nov 5.
• [10] Preclinical testing of the Akt inhibitor triciribine in T-cell acute lymphoblastic leukemia. J Cell Physiol. 2011 Mar;226(3):822-31. doi: 10.1002/jcp.22407.