Details of the Drug Combination

General Information of Drug Combination (ID: DCKC3D6)

• Drug Combination Name: ABIRATERONE + Plicamycin
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T-47D
  Zero Interaction Potency (ZIP) Score: 23.61
  Bliss Independence Score: 26.13
  Loewe Additivity Score: 25.12
  LHighest Single Agent (HSA) Score: 25.32

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[6]

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Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[4]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	[8]

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	[9]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[10]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[11]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[12]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[7]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[11]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[13]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCM3SEG	HL-60(TB)	Investigative	[15]
Adult T acute lymphoblastic leukemia	DCLRX99	MOLT-4	Investigative	[15]
Astrocytoma	DCSSNM4	U251	Investigative	[15]
Astrocytoma	DCW9DMG	SNB-19	Investigative	[15]
Childhood T acute lymphoblastic leukemia	DCG14QT	CCRF-CEM	Investigative	[15]
Chronic myelogenous leukemia	DCY8SRU	K-562	Investigative	[15]
Clear cell renal cell carcinoma	DCHM91D	786-0	Investigative	[15]
Clear cell renal cell carcinoma	DCM9G39	A498	Investigative	[15]
Clear cell renal cell carcinoma	DCX3VDW	TK-10	Investigative	[15]
Clear cell renal cell carcinoma	DC15MP5	CAKI-1	Investigative	[15]
Glioblastoma	DCK9BT7	SNB-75	Investigative	[15]
Glioma	DCWHA60	SF-295	Investigative	[15]
Glioma	DCUFL1V	SF-539	Investigative	[15]
Papillary renal cell carcinoma	DCC78EE	ACHN	Investigative	[15]
Plasma cell myeloma	DCEWB22	RPMI-8226	Investigative	[15]
Renal cell carcinoma	DC4YK5L	UO-31	Investigative	[15]
Renal cell carcinoma	DCUYOOI	SN12C	Investigative	[15]
Breast adenocarcinoma	DC3A52F	MDA-MB-468	Investigative	[1]
Carcinoma	DCC0NXQ	MCF7	Investigative	[1]
Colon adenocarcinoma	DC20TBS	COLO 205	Investigative	[1]
Colon carcinoma	DCJIWN6	KM12	Investigative	[1]
Invasive ductal carcinoma	DCBCYQ1	BT-549	Investigative	[1]
Invasive ductal carcinoma	DCK3LOJ	HS 578T	Investigative	[1]
Adenocarcinoma	DCP4C65	DU-145	Investigative	[16]
Adenocarcinoma	DC08NY5	OVCAR3	Investigative	[16]
Adenocarcinoma	DCDKMVK	HCT116	Investigative	[16]
Amelanotic melanoma	DCKR6JF	M14	Investigative	[16]
Amelanotic melanoma	DCI5JL6	MDA-MB-435	Investigative	[16]
Cutaneous melanoma	DCXSE44	SK-MEL-28	Investigative	[16]
Cutaneous melanoma	DC8I3XG	SK-MEL-5	Investigative	[16]
High grade ovarian serous adenocarcinoma	DCJ2GEH	OVCAR-8	Investigative	[16]
High grade ovarian serous adenocarcinoma	DC0TMU8	OVCAR-4	Investigative	[16]
High grade ovarian serous adenocarcinoma	DCNIN8Z	OVCAR-5	Investigative	[16]
Large cell lung carcinoma	DC4ID0K	NCI-H460	Investigative	[16]
Lung adenocarcinoma	DCYA9D8	MDA-MB-231	Investigative	[16]
Lung adenocarcinoma	DC2QCZE	NCI-H522	Investigative	[16]
Malignant melanoma	DCO7KCZ	UACC62	Investigative	[16]
Malignant melanoma	DCXANDV	LOX IMVI	Investigative	[16]
Melanoma	DCO8MWI	UACC-257	Investigative	[16]
Melanoma	DCTAERX	SK-MEL-2	Investigative	[16]
Minimally invasive lung adenocarcinoma	DC2TZ3Q	NCI-H322M	Investigative	[16]
Mixed endometrioid and clear cell carcinoma	DCOORA0	IGROV1	Investigative	[16]
Ovarian serous cystadenocarcinoma	DC088NU	SK-OV-3	Investigative	[16]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165
• [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: 6745).
• [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] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [7] 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.
• [8] Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [16] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976