Details of the Drug Combination

General Information of Drug Combination (ID: DC17J7T)

• Drug Combination Name: Ruxolitinib + Bleomycin
• Indication: Astrocytoma; Status: Investigative [1]
• Component Drugs:
  Ruxolitinib (DM7Q98D): Small molecular drug
  Bleomycin (DMNER5S): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SNB-19
  Zero Interaction Potency (ZIP) Score: 15.81
  Bliss Independence Score: 12.78
  Loewe Additivity Score: 0.43
  LHighest Single Agent (HSA) Score: 10.53

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 Bleomycin

Disease Entry	ICD 11	Status	REF
Cervical cancer	2C77.0	Approved	[8]
Head and neck cancer	2D42	Approved	[8]
Hodgkin lymphoma	2B30	Approved	[9]
Penile cancer	N.A.	Approved	[8]
Testicular germ cell tumor	N.A.	Approved	[8]
Classic Hodgkin lymphoma	N.A.	Investigative	[8]
Follicular lymphoma	2A80	Investigative	[8]

Bleomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[18]

Bleomycin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Bleomycin hydrolase (BLMH)	DECH1VP	BLMH_HUMAN	Metabolism	[19]

Bleomycin Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bleomycin hydrolase (BLMH)	OT2QPWQJ	BLMH_HUMAN	Affects Response To Substance	[20]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[21]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Expression	[21]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[21]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Increases Expression	[22]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Expression	[22]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[22]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Increases Expression	[22]
Mucin-5AC (MUC5AC)	OTJV8O04	MUC5A_HUMAN	Increases Expression	[22]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Increases Expression	[22]
Transmembrane protein 250 (TMEM250)	OTLJ4G5G	TM250_HUMAN	Increases Expression	[14]
Suppressor of cytokine signaling 1 (SOCS1)	OTWA9KFU	SOCS1_HUMAN	Decreases Expression	[23]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[24]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[15]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[25]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[15]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[15]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[26]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[15]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[27]
Cathepsin S (CTSS)	OT3PXIPM	CATS_HUMAN	Increases Expression	[28]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[29]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Decreases Expression	[14]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Increases Expression	[15]
Unconventional myosin-Ie (MYO1E)	OTM9YSIZ	MYO1E_HUMAN	Decreases Expression	[14]
Transcription intermediary factor 1-beta (TRIM28)	OTE38OBF	TIF1B_HUMAN	Increases Phosphorylation	[24]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[24]
Structural maintenance of chromosomes protein 1A (SMC1A)	OT9ZMRK9	SMC1A_HUMAN	Increases Phosphorylation	[24]
7SK snRNA methylphosphate capping enzyme (MEPCE)	OTRBQEYP	MEPCE_HUMAN	Increases Expression	[14]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[14]
Terminal nucleotidyltransferase 4B (TENT4B)	OTUF6FWW	PAPD5_HUMAN	Decreases Expression	[14]
Lipase member H (LIPH)	OTRGYLKL	LIPH_HUMAN	Decreases Expression	[14]
Abasic site processing protein HMCES (HMCES)	OTVRDL6U	HMCES_HUMAN	Decreases Expression	[14]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[14]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[14]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)	OT9I1XUO	CEIP2_HUMAN	Decreases Expression	[14]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Decreases Expression	[14]
Transmembrane and coiled-coil domain protein 3 (TMCC3)	OTAIQ6V6	TMCC3_HUMAN	Decreases Expression	[14]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)	OT27CCUF	SIAT9_HUMAN	Decreases Expression	[14]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[30]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Affects Response To Substance	[31]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCT49AZ	MOLT-4	Investigative	[1]
Chronic myelogenous leukemia	DCMEO4P	K-562	Investigative	[1]
Renal cell carcinoma	DCZ5XTU	SN12C	Investigative	[1]
Carcinoma	DC95FTC	MCF7	Investigative	[32]
Colon carcinoma	DCVND6T	KM12	Investigative	[32]
Adenocarcinoma	DCF5AJ0	DU-145	Investigative	[33]
Adenocarcinoma	DCP0ZND	A549	Investigative	[33]
Lung adenocarcinoma	DCK63BX	EKVX	Investigative	[33]
Lung adenocarcinoma	DCF8CKM	MDA-MB-231	Investigative	[33]
Malignant melanoma	DC8KX8J	LOX IMVI	Investigative	[33]

References

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• [21] Age-dependent basal level and induction capacity of copper-zinc and manganese superoxide dismutase and other scavenging enzyme activities in leukocytes from young and elderly adults. Am J Pathol. 1993 Jul;143(1):312-20.
• [22] Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells. Toxicol In Vitro. 2008 Oct;22(7):1782-8.
• [23] Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
• [24] Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun 16;9(6):e97969. doi: 10.1371/journal.pone.0097969. eCollection 2014.
• [25] Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. J Immunol. 1993 May 1;150(9):4188-96.
• [26] Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways. Chem Biol Interact. 2016 Mar 5;247:1-10. doi: 10.1016/j.cbi.2016.01.012. Epub 2016 Jan 29.
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• [31] DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008 Jan;28(2):752-71. doi: 10.1128/MCB.01799-07. Epub 2007 Nov 8.
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