Details of the Drug Combination

General Information of Drug Combination (ID: DC4SC6P)

• Drug Combination Name: GSK618334 + PD-0325901
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  GSK618334 (DMJPXZ4): Small molecular drug
  PD-0325901 (DM27D4J): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 1.305
  Bliss Independence Score: 1.025
  Loewe Additivity Score: 0.439
  LHighest Single Agent (HSA) Score: 1.718

Molecular Interaction Atlas of This Drug Combination

Indication(s) of GSK618334

Disease Entry	ICD 11	Status	REF
Drug abuse	6C4G.1Z	Phase 1	[2]
Nasopharyngeal carcinoma	2B6B	Investigative	[3]

GSK618334 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Antagonist	[5]
Sphingosine kinase 1 (SPHK1)	TTOHFIY	SPHK1_HUMAN	Inhibitor	[3]

GSK618334 Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 4F2 (CYP4F2)	DE3GT9C	CP4F2_HUMAN	Metabolism	[6]

GSK618334 Interacts with 47 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[7]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[7]
Isopentenyl-diphosphate Delta-isomerase 1 (IDI1)	OTGM06VJ	IDI1_HUMAN	Increases Expression	[7]
Squalene monooxygenase (SQLE)	OT0GGRDO	ERG1_HUMAN	Increases Expression	[7]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[7]
Programmed cell death protein 4 (PDCD4)	OTZ6NXUX	PDCD4_HUMAN	Increases Expression	[7]
Kelch-like protein 24 (KLHL24)	OTWZSX5C	KLH24_HUMAN	Increases Expression	[7]
Protein FAM200C (FAM200C)	OTZOXUEK	F200C_HUMAN	Increases Expression	[7]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[8]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[8]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Expression	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[8]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[8]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Decreases Expression	[8]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Expression	[8]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Decreases Expression	[8]
NPC intracellular cholesterol transporter 1 (NPC1)	OTRIPICX	NPC1_HUMAN	Increases Expression	[9]
Ubiquitin-like protein ATG12 (ATG12)	OTJRO09Y	ATG12_HUMAN	Increases Expression	[10]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[10]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[9]
T-cell surface glycoprotein CD8 alpha chain (CD8A)	OTDWQJXK	CD8A_HUMAN	Decreases Expression	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Phosphorylation	[10]
T-cell surface glycoprotein CD3 epsilon chain (CD3E)	OT13LE5J	CD3E_HUMAN	Decreases Expression	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[10]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[11]
T-cell-specific surface glycoprotein CD28 (CD28)	OTT5XJST	CD28_HUMAN	Decreases Expression	[11]
B-lymphocyte antigen CD19 (CD19)	OTCPF9NF	CD19_HUMAN	Decreases Expression	[11]
Transcription factor E3 (TFE3)	OTM99ZWH	TFE3_HUMAN	Decreases Phosphorylation	[12]
Sphingosine 1-phosphate receptor 1 (S1PR1)	OTLTXDQT	S1PR1_HUMAN	Decreases Activity	[13]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[10]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[10]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[11]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[10]
C-C chemokine receptor type 7 (CCR7)	OTHFUOYE	CCR7_HUMAN	Decreases Expression	[11]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[10]
C-C chemokine receptor type 4 (CCR4)	OT68KZ9B	CCR4_HUMAN	Decreases Expression	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[14]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[10]
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1)	OTC41R1E	RIPK1_HUMAN	Increases Expression	[10]
Histone deacetylase 1 (HDAC1)	OTQDNOXZ	HDAC1_HUMAN	Affects Binding	[15]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[10]
Forkhead box protein P3 (FOXP3)	OTA9Z9OC	FOXP3_HUMAN	Decreases Expression	[11]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[10]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)	OT28VBVK	ATG3_HUMAN	Increases Expression	[10]
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	OTL1D484	RIPK3_HUMAN	Increases Expression	[10]
Sphingosine kinase 2 (SPHK2)	OTNFG52M	SPHK2_HUMAN	Increases Phosphorylation	[15]

Indication(s) of PD-0325901

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[4]

PD-0325901 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[17]

PD-0325901 Interacts with 84 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[18]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[18]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Expression	[18]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Decreases Expression	[18]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Decreases Expression	[16]
Neuropilin-1 (NRP1)	OTCGULYV	NRP1_HUMAN	Decreases Expression	[16]
T-box transcription factor TBX3 (TBX3)	OTM64N7K	TBX3_HUMAN	Decreases Expression	[16]
Protein sprouty homolog 2 (SPRY2)	OTH0CRCZ	SPY2_HUMAN	Decreases Expression	[16]
Leupaxin (LPXN)	OTUNV3CK	LPXN_HUMAN	Decreases Expression	[16]
PR domain zinc finger protein 1 (PRDM1)	OTQLSVBS	PRDM1_HUMAN	Decreases Expression	[16]
Slit homolog 2 protein (SLIT2)	OTLS2RJ4	SLIT2_HUMAN	Decreases Expression	[16]
Tumor necrosis factor ligand superfamily member 15 (TNFSF15)	OTNGA2BW	TNF15_HUMAN	Decreases Expression	[16]
Integrin beta-like protein 1 (ITGBL1)	OTJDHE17	ITGBL_HUMAN	Decreases Expression	[16]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Decreases Expression	[16]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[16]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[16]
Glycophorin-C (GYPC)	OTOEDR7O	GLPC_HUMAN	Decreases Expression	[16]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[16]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[16]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Decreases Expression	[16]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Expression	[16]
Aminopeptidase N (ANPEP)	OTP3WYFD	AMPN_HUMAN	Decreases Expression	[16]
Integrin alpha-2 (ITGA2)	OTPFL017	ITA2_HUMAN	Decreases Expression	[16]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Decreases Expression	[16]
Pentraxin-related protein PTX3 (PTX3)	OTPXHRKU	PTX3_HUMAN	Decreases Expression	[16]
5-hydroxytryptamine receptor 7 (HTR7)	OT44DEWB	5HT7R_HUMAN	Decreases Expression	[16]
Glutaredoxin-1 (GLRX)	OT0QHTAR	GLRX1_HUMAN	Decreases Expression	[16]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[16]
ETS translocation variant 5 (ETV5)	OTE2OBM4	ETV5_HUMAN	Decreases Expression	[16]
ETS translocation variant 4 (ETV4)	OT8C98UZ	ETV4_HUMAN	Decreases Expression	[16]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[16]
ETS translocation variant 1 (ETV1)	OT6PMJIK	ETV1_HUMAN	Decreases Expression	[16]
Stanniocalcin-1 (STC1)	OTGVVXYF	STC1_HUMAN	Decreases Expression	[16]
Paired mesoderm homeobox protein 1 (PRRX1)	OTTZK5G8	PRRX1_HUMAN	Decreases Expression	[16]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Decreases Expression	[16]
Forkhead box protein G1 (FOXG1)	OTAW57J4	FOXG1_HUMAN	Decreases Expression	[16]
ADP-ribosylation factor-like protein 4C (ARL4C)	OTQ3QNNU	ARL4C_HUMAN	Decreases Expression	[16]
Reelin (RELN)	OTLKMW1O	RELN_HUMAN	Decreases Expression	[16]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[16]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Decreases Expression	[16]
Urokinase plasminogen activator surface receptor (PLAUR)	OTIRKKEQ	UPAR_HUMAN	Decreases Expression	[16]
Dual specificity protein phosphatase 4 (DUSP4)	OT6WAO12	DUS4_HUMAN	Decreases Expression	[16]
Semaphorin-3A (SEMA3A)	OTQJSV7W	SEM3A_HUMAN	Decreases Expression	[16]
Monocyte to macrophage differentiation factor (MMD)	OTB5I4OC	PAQRB_HUMAN	Decreases Expression	[16]
Syntaxin-1A (STX1A)	OTSBUZB4	STX1A_HUMAN	Decreases Expression	[16]
Dual specificity protein phosphatase 6 (DUSP6)	OT4H6RKW	DUS6_HUMAN	Decreases Expression	[16]
Kinesin-like protein KIF24 (KIF24)	OTJTA5V3	KIF24_HUMAN	Decreases Expression	[16]
Anoctamin-1 (ANO1)	OTSREUNI	ANO1_HUMAN	Decreases Expression	[16]
NADH-cytochrome b5 reductase 2 (CYB5R2)	OTTLM7XN	NB5R2_HUMAN	Decreases Expression	[16]
Dynamin-binding protein (DNMBP)	OTMHH14H	DNMBP_HUMAN	Decreases Expression	[16]
Sialic acid-binding Ig-like lectin 15 (SIGLEC15)	OTON4K9S	SIG15_HUMAN	Decreases Expression	[16]
UPF0606 protein KIAA1549L (KIAA1549L)	OT80HUVY	K154L_HUMAN	Decreases Expression	[16]
Neuron navigator 3 (NAV3)	OT97M1TR	NAV3_HUMAN	Decreases Expression	[16]
Dedicator of cytokinesis protein 4 (DOCK4)	OTH3XY8B	DOCK4_HUMAN	Decreases Expression	[16]
Transmembrane protein 156 (TMEM156)	OTH7YJID	TM156_HUMAN	Decreases Expression	[16]
Tribbles homolog 2 (TRIB2)	OTHSX3MX	TRIB2_HUMAN	Decreases Expression	[16]
Hyaluronan synthase 2 (HAS2)	OTTD3PAL	HYAS2_HUMAN	Decreases Expression	[16]
Neuronal cell adhesion molecule (NRCAM)	OT80HHQ2	NRCAM_HUMAN	Decreases Expression	[16]
Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2)	OTB71I02	DCBD2_HUMAN	Decreases Expression	[16]
Formin-like protein 2 (FMNL2)	OT9OVWCV	FMNL2_HUMAN	Decreases Expression	[16]
Monoglyceride lipase (MGLL)	OT5ES4IE	MGLL_HUMAN	Decreases Expression	[16]
Paternally-expressed gene 3 protein (PEG3)	OTHQW98S	PEG3_HUMAN	Decreases Expression	[16]
Disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)	OTH88TXU	ADA19_HUMAN	Decreases Expression	[16]
Sodium-dependent neutral amino acid transporter B(0)AT2 (SLC6A15)	OTGMPVNR	S6A15_HUMAN	Decreases Expression	[16]
Endothelial cell-specific molecule 1 (ESM1)	OT331Y8V	ESM1_HUMAN	Decreases Expression	[16]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_HUMAN	Decreases Expression	[16]
Neurotrimin (NTM)	OTHF0UQU	NTRI_HUMAN	Decreases Expression	[16]
Histone deacetylase 9 (HDAC9)	OTO8O0LF	HDAC9_HUMAN	Decreases Expression	[16]
Type 2 lactosamine alpha-2,3-sialyltransferase (ST3GAL6)	OTB17Q43	SIA10_HUMAN	Decreases Expression	[16]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[19]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Expression	[20]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[21]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Decreases Expression	[22]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[23]
Fos-related antigen 1 (FOSL1)	OT9YTYMB	FOSL1_HUMAN	Decreases Expression	[24]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[25]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[25]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[23]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[26]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Decreases Activity	[27]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[19]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[23]
DNA repair endonuclease XPF (ERCC4)	OTFIOPG1	XPF_HUMAN	Increases Expression	[22]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Affects Response To Substance	[28]

References

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