Details of the Drug Combination

General Information of Drug Combination (ID: DCJ5WF6)

• Drug Combination Name: MK-1775 + Docetaxel
• Indication: Ewing sarcoma; Status: Investigative [1]
• Component Drugs:
  MK-1775 (DM3WDZ5): Small molecular drug
  Docetaxel (DMDI269): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-71
  Zero Interaction Potency (ZIP) Score: 21.541
  Bliss Independence Score: 21.138
  Loewe Additivity Score: 10.261
  LHighest Single Agent (HSA) Score: 13.833

Molecular Interaction Atlas of This Drug Combination

Indication(s) of MK-1775

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

MK-1775 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Wee1-like protein kinase (WEE1)	TTJFOAL	WEE1_HUMAN	Inhibitor	[7]

MK-1775 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Phosphorylation	[6]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Response To Substance	[6]

Indication(s) of Docetaxel

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Breast carcinoma	N.A.	Approved	[4]
Head and neck cancer	2D42	Approved	[4]
Leiomyosarcoma	2B58	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Prostate adenocarcinoma	N.A.	Approved	[4]
Prostate cancer	2C82.0	Approved	[4]
Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Urinary system neoplasm	N.A.	Approved	[4]
Gastric cancer	2B72	Investigative	[4]

Docetaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[11]

Docetaxel Interacts with 8 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[12]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[13]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[15]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[16]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[17]
TAP-like protein (ABCB9)	DT68UV2	ABCB9_HUMAN	Substrate	[18]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[19]

Docetaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[20]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[21]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[21]

Docetaxel Interacts with 83 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[22]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases ADR	[23]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[24]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[22]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[25]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[27]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[27]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[27]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[27]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[27]
Dihydropyrimidine dehydrogenase (DPYD)	OTWRF2NR	DPYD_HUMAN	Decreases Activity	[8]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[28]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[28]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Degradation	[29]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[30]
PC4 and SFRS1-interacting protein (PSIP1)	OT4YAFUS	PSIP1_HUMAN	Increases Cleavage	[31]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Increases Expression	[32]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Secretion	[33]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[9]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[34]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Increases Phosphorylation	[35]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[36]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Activity	[37]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[38]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[34]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Expression	[39]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[40]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[41]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Decreases Expression	[42]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Decreases Expression	[42]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[37]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[43]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[32]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[32]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[42]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[44]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[31]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[45]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[25]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[46]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[47]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[9]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Increases Cleavage	[48]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[49]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[29]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[48]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Activity	[29]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[29]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[42]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[42]
Protein FAM117A (FAM117A)	OT2FBGGV	F117A_HUMAN	Decreases Expression	[42]
Delta-like protein 4 (DLL4)	OTRA4K2V	DLL4_HUMAN	Increases Expression	[46]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19)	OTTVT4MB	TNR19_HUMAN	Decreases Expression	[42]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Decreases Expression	[42]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Affects Response To Substance	[50]
Kinesin heavy chain isoform 5A (KIF5A)	OT3ETTI6	KIF5A_HUMAN	Decreases Response To Substance	[51]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Response To Substance	[52]
ATP-binding cassette sub-family G member 1 (ABCG1)	OT5BG6MK	ABCG1_HUMAN	Affects Response To Substance	[50]
Regulator of G-protein signaling 17 (RGS17)	OT5RVUDS	RGS17_HUMAN	Increases Response To Substance	[53]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Affects Response To Substance	[54]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[55]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[56]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Response To Substance	[57]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Affects Response To Substance	[50]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Response To Substance	[22]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Response To Substance	[58]
Kinesin-like protein KIFC3 (KIFC3)	OTOPD4QO	KIFC3_HUMAN	Decreases Response To Substance	[51]
Regulator of G-protein signaling 10 (RGS10)	OTQ8N1QH	RGS10_HUMAN	Increases Response To Substance	[53]
E3 ubiquitin-protein ligase CHFR (CHFR)	OTRAD2TT	CHFR_HUMAN	Decreases Response To Substance	[59]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[60]
Cell surface glycoprotein MUC18 (MCAM)	OTT8XKGE	MUC18_HUMAN	Decreases Response To Substance	[61]
Kinesin-like protein KIF12 (KIF12)	OTTALNDD	KIF12_HUMAN	Decreases Response To Substance	[51]
Nucleophosmin (NPM1)	OTTBYYT0	NPM_HUMAN	Decreases Response To Substance	[62]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Affects Response To Substance	[50]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Increases Response To Substance	[22]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Response To Substance	[63]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Affects Response To Substance	[54]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Affects Response To Substance	[64]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Affects Response To Substance	[65]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Response To Substance	[50]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Affects Response To Substance	[50]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Lung Cancer	DCD4BKP	N. A.	Phase 2	[66]

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