Details of the Drug Combination

General Information of Drug Combination (ID: DCXXD9Y)

• Drug Combination Name: Cabazitaxel + Plicamycin
• Indication: Melanoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: UACC-257
  Zero Interaction Potency (ZIP) Score: 25.06
  Bliss Independence Score: 20.62
  Loewe Additivity Score: 11.82
  LHighest Single Agent (HSA) Score: 21.57

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Metastatic prostate carcinoma	N.A.	Investigative	[3]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[7]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[9]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[9]

Indication(s) of Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[4]
Testicular cancer	2C80	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[5]
Lung cancer	2C25.0	Investigative	[6]
Ovarian cancer	2C73	Investigative	[6]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[11]

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	[12]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[13]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[14]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[15]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[10]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[14]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[16]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[17]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC6MA2T	HCC-2998	Investigative	[1]
Adult acute myeloid leukemia	DCFKIO7	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCW4KUL	MOLT-4	Investigative	[1]
Anaplastic large cell lymphoma	DC7912S	SR	Investigative	[1]
Astrocytoma	DCBSFP9	U251	Investigative	[1]
Astrocytoma	DCARKRK	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCQLT1P	CCRF-CEM	Investigative	[1]
Clear cell renal cell carcinoma	DC3APSN	A498	Investigative	[1]
Clear cell renal cell carcinoma	DC88NCY	786-0	Investigative	[1]
Cutaneous melanoma	DCRN3ZN	SK-MEL-28	Investigative	[1]
Cutaneous melanoma	DCZ6FN5	SK-MEL-5	Investigative	[1]
Glioblastoma	DCZHY12	SNB-75	Investigative	[1]
Glioma	DCD4UUV	SF-539	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCY037T	OVCAR-8	Investigative	[1]
Lung adenocarcinoma	DCQ2IHU	MDA-MB-231	Investigative	[1]
Malignant melanoma	DC747PX	UACC62	Investigative	[1]
Non-small cell lung carcinoma	DCBS5KM	HOP-92	Investigative	[1]
Papillary renal cell carcinoma	DC4GTW3	ACHN	Investigative	[1]
Breast adenocarcinoma	DCBLV1H	MDA-MB-468	Investigative	[18]
Carcinoma	DCASK5E	MCF7	Investigative	[18]
Invasive ductal carcinoma	DC7Z603	T-47D	Investigative	[18]
Invasive ductal carcinoma	DCI8H5T	HS 578T	Investigative	[18]
Invasive ductal carcinoma	DCBZD4E	BT-549	Investigative	[18]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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: 6798).
• [3] Cabazitaxel FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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).
• [6] The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
• [7] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [8] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [9] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [10] 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.
• [11] Role of magnesium ion in mithramycin-DNA interaction: binding of mithramycin-Mg2+ complexes with DNA. Biochemistry. 1995 Jan 31;34(4):1376-85.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165