Details of the Drug Combination

General Information of Drug Combination (ID: DC5BO42)

• Drug Combination Name: Ruxolitinib + Plicamycin
• Indication: Colon carcinoma; Status: Investigative [1]
• Component Drugs:
  Ruxolitinib (DM7Q98D): Small molecular drug
  Plicamycin (DM7C8YV): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KM12
  Zero Interaction Potency (ZIP) Score: 10.65
  Bliss Independence Score: 8.94
  Loewe Additivity Score: 8.65
  LHighest Single Agent (HSA) Score: 8.86

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[2]
High-risk myelofibrosis	2A20.2	Approved	[3]
Myelofibrosis	2A22	Approved	[4]
Myeloproliferative neoplasm	2A20	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Pancreatic cancer	2C10	Phase 3	[3]
Atopic dermatitis	EA80	Phase 1/2	[7]
Vitiligo	ED63.0	Phase 1/2	[7]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[10]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[10]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[11]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[12]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[12]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[13]

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Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[8]
Lung cancer	2C25.0	Investigative	[9]
Ovarian cancer	2C73	Investigative	[9]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[15]

Plicamycin Interacts with 16 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	[16]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[17]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Decreases Expression	[17]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Expression	[17]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[18]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[18]
Epoxide hydrolase 1 (EPHX1)	OTBKWQER	HYEP_HUMAN	Decreases Expression	[19]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Expression	[14]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[20]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[21]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[22]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[14]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[23]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[20]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[24]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[25]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DCAK2AJ	HL-60(TB)	Investigative	[26]
Adult T acute lymphoblastic leukemia	DCVQCXX	MOLT-4	Investigative	[26]
Anaplastic large cell lymphoma	DC7I3LT	SR	Investigative	[26]
Astrocytoma	DCMRJUI	U251	Investigative	[26]
Astrocytoma	DCP0UVE	SNB-19	Investigative	[26]
Childhood T acute lymphoblastic leukemia	DCSZ29A	CCRF-CEM	Investigative	[26]
Chronic myelogenous leukemia	DCT8TVE	K-562	Investigative	[26]
Clear cell renal cell carcinoma	DCMGNCV	TK-10	Investigative	[26]
Clear cell renal cell carcinoma	DCYJKW4	A498	Investigative	[26]
Clear cell renal cell carcinoma	DC0MDOV	786-0	Investigative	[26]
Clear cell renal cell carcinoma	DCN1A5J	CAKI-1	Investigative	[26]
Glioma	DCFUV3H	SF-539	Investigative	[26]
Glioma	DCOXTVC	SF-295	Investigative	[26]
Papillary renal cell carcinoma	DCFL78I	ACHN	Investigative	[26]
Plasma cell myeloma	DC46V0X	RPMI-8226	Investigative	[26]
Carcinoma	DC6XBKU	MCF7	Investigative	[1]
Colon adenocarcinoma	DC4G2QL	COLO 205	Investigative	[1]
Invasive ductal carcinoma	DC29QEU	T-47D	Investigative	[1]
Invasive ductal carcinoma	DCR4RZQ	BT-549	Investigative	[1]
Invasive ductal carcinoma	DCDFJDH	HS 578T	Investigative	[1]
Adenocarcinoma	DCROKN8	OVCAR3	Investigative	[27]
Adenocarcinoma	DC47ZNK	SW-620	Investigative	[27]
Adenocarcinoma	DCI2M9Q	HCT-15	Investigative	[27]
Adenocarcinoma	DC0848B	HCT116	Investigative	[27]
Adenocarcinoma	DCL0QDL	HCC-2998	Investigative	[27]
Amelanotic melanoma	DCYYZBV	MDA-MB-435	Investigative	[27]
Cutaneous melanoma	DCD1MDI	SK-MEL-28	Investigative	[27]
Cutaneous melanoma	DC9YSLR	SK-MEL-5	Investigative	[27]
High grade ovarian serous adenocarcinoma	DCULFUI	OVCAR-5	Investigative	[27]
High grade ovarian serous adenocarcinoma	DC0QRAK	OVCAR-8	Investigative	[27]
High grade ovarian serous adenocarcinoma	DCS3AML	OVCAR-4	Investigative	[27]
Large cell lung carcinoma	DCFY4S1	NCI-H460	Investigative	[27]
Melanoma	DCK0CZ0	UACC-257	Investigative	[27]
Melanoma	DCB9JW5	SK-MEL-2	Investigative	[27]
Melanoma	DC2XXRV	MALME-3M	Investigative	[27]
Minimally invasive lung adenocarcinoma	DCZSVC1	NCI-H322M	Investigative	[27]
Non-small cell lung carcinoma	DC700ZP	HOP-92	Investigative	[27]
Prostate carcinoma	DCA079H	PC-3	Investigative	[27]

References

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• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Ruxolitinib FDA Label
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• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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).
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• [19] Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter. Gene. 2014 Feb 15;536(1):135-44. doi: 10.1016/j.gene.2013.11.053. Epub 2013 Dec 4.
• [20] 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.
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• [22] 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.
• [23] CREB/Sp1-mediated MCL1 expression and NFB-mediated ABCB1 expression modulate the cytotoxicity of daunorubicin in chronic myeloid leukemia cells. Toxicol Appl Pharmacol. 2022 Jan 15;435:115847. doi: 10.1016/j.taap.2021.115847. Epub 2021 Dec 25.
• [24] 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.
• [25] 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.
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