Details of the Drug Combination

General Information of Drug Combination (ID: DCP6EAN)

• Drug Combination Name: Plicamycin + Nilotinib
• Indication: Cutaneous melanoma; Status: Investigative [1]
• Component Drugs:
  Plicamycin (DM7C8YV): Small molecular drug
  Nilotinib (DM7HXWT): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SK-MEL-28
  Zero Interaction Potency (ZIP) Score: 0.87
  Bliss Independence Score: 1.57
  Loewe Additivity Score: 0.28
  LHighest Single Agent (HSA) Score: 1.65

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Plicamycin

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[2]
Testicular cancer	2C80	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Withdrawn from market	[3]
Lung cancer	2C25.0	Investigative	[4]
Ovarian cancer	2C73	Investigative	[4]

Plicamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
RNA synthesis (hRNA synth)	TTX2AYW	NOUNIPROTAC	Modulator	[7]

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	[8]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[9]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Decreases Expression	[9]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Expression	[9]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[10]
Epoxide hydrolase 1 (EPHX1)	OTBKWQER	HYEP_HUMAN	Decreases Expression	[11]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Expression	[6]
Proto-oncogene tyrosine-protein kinase Src (SRC)	OTETYX40	SRC_HUMAN	Decreases Expression	[12]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[13]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Decreases Expression	[14]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Expression	[6]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[15]
Epidermal growth factor receptor kinase substrate 8 (EPS8)	OTZ6ES6V	EPS8_HUMAN	Decreases Expression	[12]
TNFAIP3-interacting protein 1 (TNIP1)	OTRAOTEW	TNIP1_HUMAN	Decreases Expression	[16]
Sphingomyelin phosphodiesterase 3 (SMPD3)	OTHQBETH	NSMA2_HUMAN	Decreases Expression	[17]

Indication(s) of Nilotinib

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[5]

Nilotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Modulator	[21]

Nilotinib Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[22]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[23]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[22]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[24]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[24]

Nilotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[25]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[26]

Nilotinib Interacts with 35 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Response To Substance	[27]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Response To Substance	[28]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[29]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[29]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[29]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[29]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[19]
Tyrosine-protein kinase ABL1 (ABL1)	OT09YVXH	ABL1_HUMAN	Decreases Phosphorylation	[20]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[20]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Secretion	[30]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[20]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[19]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[31]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[31]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[20]
Breakpoint cluster region protein (BCR)	OTCN76C1	BCR_HUMAN	Decreases Phosphorylation	[32]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[20]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[19]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Decreases Expression	[20]
Histidine decarboxylase (HDC)	OT4WA5YQ	DCHS_HUMAN	Decreases Expression	[33]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[19]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[34]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[19]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[20]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[20]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[20]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[19]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[31]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[19]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[19]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[19]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1)	OTWHN69S	EDEM1_HUMAN	Increases Expression	[20]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[19]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[19]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[19]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DCQQJH1	SR	Investigative	[35]
Colon adenocarcinoma	DCZOLEL	COLO 205	Investigative	[36]
Adenocarcinoma	DC6OIAY	OVCAR3	Investigative	[1]
Adenocarcinoma	DCV481J	HCT116	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCMEW1Z	OVCAR-8	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCFD8Y1	IGROV1	Investigative	[1]

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