Details of the Drug Combination

General Information of Drug Combination (ID: DCY02OX)

• Drug Combination Name: Bafilomycin A1 + Crizotinib
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Bafilomycin A1 (DMUNK59): Small molecular drug
  Crizotinib (DM4F29C): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DIPG25
  Zero Interaction Potency (ZIP) Score: 2.57
  Bliss Independence Score: 6.39
  Loewe Additivity Score: 1.98
  LHighest Single Agent (HSA) Score: 3.8

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Bafilomycin A1

Disease Entry	ICD 11	Status	REF
B-cell acute lymphoblastic leukaemia	2B33.3	Investigative	[2]

Bafilomycin A1 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vacuolar-type proton ATPase (v-ATPase)	TTTK3BH	NOUNIPROTAC	Inhibitor	[5]

Bafilomycin A1 Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptotic protease-activating factor 1 (APAF1)	OTJWIVY0	APAF_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Expression	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Expression	[6]
Steroidogenic factor 1 (NR5A1)	OTOULYR4	STF1_HUMAN	Decreases Expression	[7]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Expression	[8]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Increases Expression	[4]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Decreases Uptake	[9]
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Decreases Cleavage	[10]
Procathepsin L (CTSL)	OTYTUW29	CATL1_HUMAN	Decreases Cleavage	[10]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[12]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Increases Expression	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Activity	[14]
Caspase-4 (CASP4)	OTVQTV1L	CASP4_HUMAN	Increases Activity	[15]
Microsomal triglyceride transfer protein large subunit (MTTP)	OTNUVSDT	MTP_HUMAN	Increases Expression	[16]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Decreases Activity	[14]
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Increases Cleavage	[17]
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)	OT4SO7J4	BNIP3_HUMAN	Increases Expression	[14]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[18]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[14]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)	OTZM6MHU	NLRP3_HUMAN	Increases Expression	[4]
Microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B)	OTUYHB84	MLP3B_HUMAN	Increases Cleavage	[19]
Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)	OTPMGIU4	MLP3A_HUMAN	Increases Expression	[20]
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2)	OTLS7C99	LRRK2_HUMAN	Increases Response To Substance	[21]

Indication(s) of Crizotinib

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[3]

Crizotinib Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Modulator	[25]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[25]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[25]
HGF/Met signaling pathway (HGF/Met pathway)	TTKA5LP	NOUNIPROTAC	Inhibitor	[26]

Crizotinib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[27]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[28]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[28]

Crizotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[29]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[29]

Crizotinib Interacts with 45 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[30]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[31]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Response To Substance	[23]
ALK tyrosine kinase receptor (ALK)	OTV3P4V8	ALK_HUMAN	Decreases Response To Substance	[32]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[22]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[22]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[22]
Cytidine deaminase (CDA)	OT3HXP6N	CDD_HUMAN	Decreases Expression	[22]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[33]
Acyl-CoA 6-desaturase (FADS2)	OTUX531P	FADS2_HUMAN	Increases Expression	[33]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[33]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[33]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[33]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[33]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Expression	[33]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[33]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[33]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[33]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Decreases Activity	[33]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[23]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[23]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Secretion	[34]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[34]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Activity	[35]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[36]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[37]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[36]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[38]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[39]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[39]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[40]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[41]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Decreases Phosphorylation	[42]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[41]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[23]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[43]
Echinoderm microtubule-associated protein-like 4 (EML4)	OTJC45TA	EMAL4_HUMAN	Increases Mutagenesis	[39]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[31]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[44]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Response To Substance	[40]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[44]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Response To Substance	[32]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Response To Substance	[40]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Decreases Response To Substance	[40]

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