Details of the Drug Combination

General Information of Drug Combination (ID: DCWV777)

• Drug Combination Name: Crizotinib + Docetaxel
• Indication: Anaplastic large cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Crizotinib (DM4F29C): Small molecular drug
  Docetaxel (DMDI269): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SR
  Zero Interaction Potency (ZIP) Score: 2.72
  Bliss Independence Score: 3.64
  Loewe Additivity Score: 0.07
  LHighest Single Agent (HSA) Score: 3.78

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Crizotinib

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

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	[8]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[8]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[8]
HGF/Met signaling pathway (HGF/Met pathway)	TTKA5LP	NOUNIPROTAC	Inhibitor	[9]

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	[10]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[11]

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	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[12]

Crizotinib Interacts with 24 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[13]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Response To Substance	[6]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[5]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[5]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[14]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[14]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Expression	[14]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[14]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[14]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Decreases Activity	[14]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[6]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[6]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Secretion	[15]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[15]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Activity	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[17]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[17]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[18]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[18]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Decreases Phosphorylation	[19]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[20]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[6]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[13]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Docetaxel

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[3]
Breast carcinoma	N.A.	Approved	[3]
Head and neck cancer	2D42	Approved	[3]
Leiomyosarcoma	2B58	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Non-small-cell lung cancer	2C25.Y	Approved	[3]
Prostate adenocarcinoma	N.A.	Approved	[3]
Prostate cancer	2C82.0	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Urinary system neoplasm	N.A.	Approved	[3]
Gastric cancer	2B72	Investigative	[3]

Docetaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[25]

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	[26]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[27]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[28]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[29]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[30]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[31]
TAP-like protein (ABCB9)	DT68UV2	ABCB9_HUMAN	Substrate	[32]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[33]

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	[34]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[35]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[35]

Docetaxel Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[36]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[37]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[37]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Degradation	[38]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[39]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Increases Expression	[40]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[41]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[42]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[41]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[43]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[44]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Decreases Expression	[45]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[46]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[40]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[40]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[45]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[47]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Activity	[38]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[38]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[45]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[45]
Protein FAM117A (FAM117A)	OT2FBGGV	F117A_HUMAN	Decreases Expression	[45]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19)	OTTVT4MB	TNR19_HUMAN	Decreases Expression	[45]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Decreases Expression	[45]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Affects Response To Substance	[48]
Kinesin heavy chain isoform 5A (KIF5A)	OT3ETTI6	KIF5A_HUMAN	Decreases Response To Substance	[49]
Regulator of G-protein signaling 17 (RGS17)	OT5RVUDS	RGS17_HUMAN	Increases Response To Substance	[50]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Affects Response To Substance	[51]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[52]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Response To Substance	[53]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Response To Substance	[54]
Kinesin-like protein KIFC3 (KIFC3)	OTOPD4QO	KIFC3_HUMAN	Decreases Response To Substance	[49]
Regulator of G-protein signaling 10 (RGS10)	OTQ8N1QH	RGS10_HUMAN	Increases Response To Substance	[50]
E3 ubiquitin-protein ligase CHFR (CHFR)	OTRAD2TT	CHFR_HUMAN	Decreases Response To Substance	[55]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[56]
Kinesin-like protein KIF12 (KIF12)	OTTALNDD	KIF12_HUMAN	Decreases Response To Substance	[49]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Affects Response To Substance	[48]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Response To Substance	[57]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Affects Response To Substance	[51]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Affects Response To Substance	[58]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Affects Response To Substance	[48]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCP94OL	NCIH23	Investigative	[1]
Adenocarcinoma	DCRNS9U	A549	Investigative	[1]
Adenocarcinoma	DCE8M2E	HCC-2998	Investigative	[1]
Adenocarcinoma	DCQBU14	HCT116	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCT21SD	MOLT-4	Investigative	[1]
Astrocytoma	DCF7ID4	SNB-19	Investigative	[1]
Chronic myelogenous leukemia	DCIQ2GK	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCUKMNT	TK-10	Investigative	[1]
Large cell lung carcinoma	DCFFGBO	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCEJ0U4	MDA-MB-231	Investigative	[1]
Prostate carcinoma	DCRDRG4	PC-3	Investigative	[1]
Colon adenocarcinoma	DC4SAXT	COLO 205	Investigative	[59]

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