Details of the Drug Combination

General Information of Drug Combination (ID: DCENVZI)

• Drug Combination Name: Amonafide + Plicamycin
• Indication: Papillary renal cell carcinoma; Status: Investigative [1]
• Component Drugs:
  Amonafide (DMAH59S): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ACHN
  Zero Interaction Potency (ZIP) Score: 3.64
  Bliss Independence Score: 4.91
  Loewe Additivity Score: 2.26
  LHighest Single Agent (HSA) Score: 6.14

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 Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[3]
Testicular cancer	2C80	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[4]
Lung cancer	2C25.0	Investigative	[5]
Ovarian cancer	2C73	Investigative	[5]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[7]

Plicamycin Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[8]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[9]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[10]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[11]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[6]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[10]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[12]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCSX58R	DU-145	Investigative	[1]
Adenocarcinoma	DCQ96Q3	NCIH23	Investigative	[1]
Adenocarcinoma	DCPSYXB	HCT116	Investigative	[1]
Adenocarcinoma	DCUZLKL	HCC-2998	Investigative	[1]
Adenocarcinoma	DCW570H	HCT-15	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCIQJWI	MOLT-4	Investigative	[1]
Astrocytoma	DCGMJVI	U251	Investigative	[1]
Chronic myelogenous leukemia	DCE0OKI	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DC28KVR	786-0	Investigative	[1]
Cutaneous melanoma	DCSOCE0	SK-MEL-28	Investigative	[1]
Glioma	DCBL8S9	SF-539	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC46TU2	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC7OLNW	OVCAR-4	Investigative	[1]
Lung adenocarcinoma	DCQUAIG	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCP5JW3	NCI-H522	Investigative	[1]
Melanoma	DCIYBII	SK-MEL-2	Investigative	[1]
Melanoma	DC8FUGO	UACC-257	Investigative	[1]
Melanoma	DCA17FS	MALME-3M	Investigative	[1]
Non-small cell lung carcinoma	DC1QCII	HOP-92	Investigative	[1]
Plasma cell myeloma	DCG1MZE	RPMI-8226	Investigative	[1]
Renal cell carcinoma	DCAXL1L	SN12C	Investigative	[1]
Breast adenocarcinoma	DCM04C8	MDA-MB-468	Investigative	[14]
Carcinoma	DCHU68A	RXF 393	Investigative	[14]
Invasive ductal carcinoma	DCYNTZ4	HS 578T	Investigative	[14]
Invasive ductal carcinoma	DCMONJU	BT-549	Investigative	[14]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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: 8394).
• [5] The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
• [6] The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription. Chem Biol Interact. 2014 Aug 5;219:123-32. doi: 10.1016/j.cbi.2014.05.019. Epub 2014 Jun 4.
• [7] Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
• [8] SP1 and SP3 mediate progesterone-dependent induction of the 17beta hydroxysteroid dehydrogenase type 2 gene in human endometrium. Biol Reprod. 2006 Oct;75(4):605-14.
• [9] Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem. 2007 Jan 26;282(4):2615-25. doi: 10.1074/jbc.M606203200. Epub 2006 Nov 22.
• [10] Mithramycin inhibits human epithelial carcinoma cell proliferation and migration involving downregulation of Eps8 expression. Chem Biol Interact. 2010 Jan 5;183(1):181-6. doi: 10.1016/j.cbi.2009.09.018.
• [11] The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
• [12] Sp sites contribute to basal and inducible expression of the human TNIP1 (TNF-inducible protein 3-interacting protein 1) promoter. Biochem J. 2013 Jun 15;452(3):519-29. doi: 10.1042/BJ20121666.
• [13] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin. Biochim Biophys Acta. 2009 Nov-Dec;1789(11-12):681-90. doi: 10.1016/j.bbagrm.2009.08.006. Epub 2009 Aug 19.
• [14] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165