Details of the Drug Combination

General Information of Drug Combination (ID: DCW5ILP)

• Drug Combination Name: Bleomycin + ABT-263
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Bleomycin (DMNER5S): Small molecular drug
  ABT-263 (DMNE56X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 42.568
  Bliss Independence Score: 41.596
  Loewe Additivity Score: 5.403
  LHighest Single Agent (HSA) Score: 9.678

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Bleomycin

Disease Entry	ICD 11	Status	REF
Cervical cancer	2C77.0	Approved	[2]
Head and neck cancer	2D42	Approved	[2]
Hodgkin lymphoma	2B30	Approved	[3]
Penile cancer	N.A.	Approved	[2]
Testicular germ cell tumor	N.A.	Approved	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]

Bleomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[11]

Bleomycin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Bleomycin hydrolase (BLMH)	DECH1VP	BLMH_HUMAN	Metabolism	[12]

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	[13]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[14]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases Expression	[14]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[14]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Increases Expression	[15]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Expression	[15]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[15]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Increases Expression	[15]
Mucin-5AC (MUC5AC)	OTJV8O04	MUC5A_HUMAN	Increases Expression	[15]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Increases Expression	[15]
Transmembrane protein 250 (TMEM250)	OTLJ4G5G	TM250_HUMAN	Increases Expression	[7]
Suppressor of cytokine signaling 1 (SOCS1)	OTWA9KFU	SOCS1_HUMAN	Decreases Expression	[16]
Serine/threonine-protein kinase Chk2 (CHEK2)	OT8ZPCNS	CHK2_HUMAN	Increases Phosphorylation	[17]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[8]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[19]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[8]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[20]
Cathepsin S (CTSS)	OT3PXIPM	CATS_HUMAN	Increases Expression	[21]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Increases Phosphorylation	[22]
Max-interacting protein 1 (MXI1)	OTUQ9E0D	MXI1_HUMAN	Decreases Expression	[7]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Increases Expression	[8]
Unconventional myosin-Ie (MYO1E)	OTM9YSIZ	MYO1E_HUMAN	Decreases Expression	[7]
Transcription intermediary factor 1-beta (TRIM28)	OTE38OBF	TIF1B_HUMAN	Increases Phosphorylation	[17]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Phosphorylation	[17]
Structural maintenance of chromosomes protein 1A (SMC1A)	OT9ZMRK9	SMC1A_HUMAN	Increases Phosphorylation	[17]
7SK snRNA methylphosphate capping enzyme (MEPCE)	OTRBQEYP	MEPCE_HUMAN	Increases Expression	[7]
Transmembrane protein 87A (TMEM87A)	OT8ATDVX	TM87A_HUMAN	Increases Expression	[7]
Terminal nucleotidyltransferase 4B (TENT4B)	OTUF6FWW	PAPD5_HUMAN	Decreases Expression	[7]
Lipase member H (LIPH)	OTRGYLKL	LIPH_HUMAN	Decreases Expression	[7]
Abasic site processing protein HMCES (HMCES)	OTVRDL6U	HMCES_HUMAN	Decreases Expression	[7]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[7]
Kelch-like protein 42 (KLHL42)	OTK6WARI	KLH42_HUMAN	Increases Expression	[7]
Inactive cell surface hyaluronidase CEMIP2 (CEMIP2)	OT9I1XUO	CEIP2_HUMAN	Decreases Expression	[7]
ERBB receptor feedback inhibitor 1 (ERRFI1)	OT7VZ2IZ	ERRFI_HUMAN	Decreases Expression	[7]
Transmembrane and coiled-coil domain protein 3 (TMCC3)	OTAIQ6V6	TMCC3_HUMAN	Decreases Expression	[7]
Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)	OT27CCUF	SIAT9_HUMAN	Decreases Expression	[7]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[23]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Affects Response To Substance	[24]

Indication(s) of ABT-263

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Phase 3	[4]
Relapsed or refractory chronic lymphocytic leukaemia	2A82.0	Phase 2	[5]
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[6]

ABT-263 Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-W (BCL-W)	TTQ79W8	B2CL2_HUMAN	Inhibitor	[25]
G1/S-specific cyclin-D1 (CCND1)	TTFCJ7S	CCND1_HUMAN	Inhibitor	[26]
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Inhibitor	[25]
Apoptosis regulator Bcl-xL (BCL-xL)	TTU1E82	B2CL1_HUMAN	Inhibitor	[25]

ABT-263 Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]

ABT-263 Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[28]

ABT-263 Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[29]
Gelsolin (GSN)	OT4KS2UU	GELS_HUMAN	Increases Cleavage	[30]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[29]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[30]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[30]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Affects Response To Substance	[29]

References

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• [13] Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis. 2002 Jun;23(6):1003-8. doi: 10.1093/carcin/23.6.1003.
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