Details of the Drug Combination

General Information of Drug Combination (ID: DCQGRQW)

• Drug Combination Name: Vemurafenib + Dactinomycin
• Indication: Plasma cell myeloma; Status: Investigative [1]
• Component Drugs:
  Vemurafenib (DM62UG5): Small molecular drug
  Dactinomycin (DM2YGNW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RPMI-8226
  Zero Interaction Potency (ZIP) Score: 10.3
  Bliss Independence Score: 12.72
  Loewe Additivity Score: 1.4
  LHighest Single Agent (HSA) Score: 9.72

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vemurafenib

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[2]

Vemurafenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Modulator	[7]

Vemurafenib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

Vemurafenib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Vemurafenib Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Microphthalmia-associated transcription factor (MITF)	OT6XJCZH	MITF_HUMAN	Affects Expression	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Expression	[12]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[6]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[6]
CD70 antigen (CD70)	OTHB2AL1	CD70_HUMAN	Decreases Expression	[14]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[12]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Decreases Expression	[15]
Melanocyte protein PMEL (PMEL)	OTCDDHHM	PMEL_HUMAN	Increases Expression	[5]
Melanoma-associated antigen 1 (MAGEA1)	OTXAO193	MAGA1_HUMAN	Decreases Expression	[5]
Thyroxine 5-deiodinase (DIO3)	OTNTITOT	IOD3_HUMAN	Decreases Expression	[16]
Melanoma antigen recognized by T-cells 1 (MLANA)	OT1N2S2K	MAR1_HUMAN	Increases Expression	[5]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Affects Response To Substance	[17]
Serine/threonine-protein kinase B-raf (BRAF)	OT7S81XQ	BRAF_HUMAN	Increases Response To Substance	[18]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Decreases Response To Substance	[19]
GTPase NRas (NRAS)	OTVQ1DG3	RASN_HUMAN	Affects Response To Substance	[17]

Indication(s) of Dactinomycin

Disease Entry	ICD 11	Status	REF
Adult kidney Wilms tumor	N.A.	Approved	[3]
Advanced cancer	2A00-2F9Z	Approved	[3]
Beckwith-Wiedemann syndrome	N.A.	Approved	[3]
Childhood kidney Wilms tumor	N.A.	Approved	[3]
Gestational trophoblastic neoplasia	2F33-2F76	Approved	[3]
Hamartoma	N.A.	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Wilms tumor	N.A.	Approved	[3]

Dactinomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[23]

Dactinomycin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[24]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[25]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[26]

Dactinomycin Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[27]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[28]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Increases Expression	[20]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[20]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[20]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases Expression	[20]
Ras-related protein R-Ras (RRAS)	OTBBF28C	RRAS_HUMAN	Increases Expression	[20]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[20]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[20]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[20]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[20]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[20]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[20]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[20]
Large ribosomal subunit protein eL34 (RPL34)	OT0U9VMQ	RL34_HUMAN	Increases Expression	[20]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[20]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[20]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[20]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[20]
Endonuclease III-like protein 1 (NTHL1)	OTPQXPT1	NTH_HUMAN	Decreases Expression	[20]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Increases Expression	[20]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[20]
Kinesin-like protein KIF1A (KIF1A)	OT3JVEGV	KIF1A_HUMAN	Increases Expression	[20]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Increases Expression	[20]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[20]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[20]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[20]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[20]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Increases Expression	[20]
Interleukin-27 receptor subunit alpha (IL27RA)	OTSQBAKI	I27RA_HUMAN	Increases Expression	[20]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[20]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Increases Expression	[20]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[20]
Homer protein homolog 3 (HOMER3)	OTQ6D9X1	HOME3_HUMAN	Increases Expression	[20]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Increases Expression	[20]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[20]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[20]
Fatty acid desaturase 3 (FADS3)	OT9RVXGE	FADS3_HUMAN	Increases Expression	[20]
Protein O-mannosyl-transferase 1 (POMT1)	OTGQSHL5	POMT1_HUMAN	Increases Expression	[20]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[29]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[30]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[31]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[32]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[33]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[34]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[33]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Decreases Expression	[35]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Response To Substance	[36]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[37]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Increases Expression	[33]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[38]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[39]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[37]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[33]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Expression	[40]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[41]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[42]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[43]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[44]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[45]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[34]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Decreases Expression	[33]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[33]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[33]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[46]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[47]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[48]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Increases Expression	[33]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[33]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Cleavage	[49]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[33]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Decreases Expression	[33]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[50]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[51]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[52]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[33]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[33]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[53]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[33]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[43]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Expression	[40]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[54]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[34]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[55]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[56]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DC6WQSH	MDA-MB-468	Investigative	[57]
Carcinoma	DCJF6IN	RXF 393	Investigative	[57]
Carcinoma	DC8D3U0	MCF7	Investigative	[57]
Colon adenocarcinoma	DC2W0GH	COLO 205	Investigative	[57]
Colon carcinoma	DCOGS3X	KM12	Investigative	[57]
Invasive ductal carcinoma	DCYYZEV	T-47D	Investigative	[57]
Invasive ductal carcinoma	DCI3XU9	BT-549	Investigative	[57]
Invasive ductal carcinoma	DCCQAKR	HS 578T	Investigative	[57]
Adenocarcinoma	DC06LVW	DU-145	Investigative	[1]
Adenocarcinoma	DCTSATO	OVCAR3	Investigative	[1]
Adenocarcinoma	DCPJ0XN	A549	Investigative	[1]
Adenocarcinoma	DCJYKYD	NCIH23	Investigative	[1]
Adenocarcinoma	DCU71LX	SW-620	Investigative	[1]
Adenocarcinoma	DCZIV2U	HT29	Investigative	[1]
Adenocarcinoma	DC1759N	HCC-2998	Investigative	[1]
Adenocarcinoma	DC0JR1W	HCT-15	Investigative	[1]
Adenocarcinoma	DCBVANE	HCT116	Investigative	[1]
Adult acute myeloid leukemia	DC6PGIV	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCD2XPX	MOLT-4	Investigative	[1]
Amelanotic melanoma	DC9N6KJ	M14	Investigative	[1]
Amelanotic melanoma	DCRX5AE	MDA-MB-435	Investigative	[1]
Anaplastic large cell lymphoma	DC418ZG	SR	Investigative	[1]
Astrocytoma	DCZEUS1	U251	Investigative	[1]
Astrocytoma	DCZYNAD	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCH0Q6L	CCRF-CEM	Investigative	[1]
Chronic myelogenous leukemia	DCJ0OT5	K-562	Investigative	[1]
Clear cell renal cell carcinoma	DCEIRZE	TK-10	Investigative	[1]
Clear cell renal cell carcinoma	DCGKDPT	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DC4F423	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCJUC4L	CAKI-1	Investigative	[1]
Cutaneous melanoma	DCS9E15	SK-MEL-5	Investigative	[1]
Cutaneous melanoma	DCHBIXH	SK-MEL-28	Investigative	[1]
Glioblastoma	DCF32YH	SNB-75	Investigative	[1]
Glioma	DCDHD51	SF-539	Investigative	[1]
Glioma	DC8B8KR	SF-268	Investigative	[1]
Glioma	DC1QIQU	SF-295	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCQBQHU	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCN2VFE	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC8KH3Z	OVCAR-4	Investigative	[1]
Large cell lung carcinoma	DCD0K4Q	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCMHSOQ	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCY3LH0	EKVX	Investigative	[1]
Lung adenocarcinoma	DCC8BIS	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCKBA62	NCI-H522	Investigative	[1]
Malignant melanoma	DC9XVRI	UACC62	Investigative	[1]
Malignant melanoma	DCG6ZHM	LOX IMVI	Investigative	[1]
Melanoma	DCRGZD3	UACC-257	Investigative	[1]
Melanoma	DCCVCA4	SK-MEL-2	Investigative	[1]
Melanoma	DCCDFJ8	MALME-3M	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCHM46W	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCVFE4B	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DC15OQ6	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCFUQ92	SK-OV-3	Investigative	[1]
Papillary renal cell carcinoma	DCOHQ47	ACHN	Investigative	[1]
Pleural epithelioid mesothelioma	DCE65UG	NCI-H226	Investigative	[1]
Prostate carcinoma	DCY3WUG	PC-3	Investigative	[1]
Renal cell carcinoma	DCRSXZV	SN12C	Investigative	[1]
Renal cell carcinoma	DCJ24KS	UO-31	Investigative	[1]

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