Details of the Drug Combination

General Information of Drug Combination (ID: DCJY4RK)

• Drug Combination Name: PD-0325901 + Gefitinib
• Indication: Primitive neuroectodermal tumor; Status: Investigative [1]
• Component Drugs:
  PD-0325901 (DM27D4J): Small molecular drug
  Gefitinib (DM15F0X): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-32
  Zero Interaction Potency (ZIP) Score: 8.66
  Bliss Independence Score: 7.92
  Loewe Additivity Score: 5.71
  LHighest Single Agent (HSA) Score: 6.95

Molecular Interaction Atlas of This Drug Combination

Indication(s) of PD-0325901

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

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	[6]

PD-0325901 Interacts with 62 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Decreases Expression	[7]
T-box transcription factor TBX3 (TBX3)	OTM64N7K	TBX3_HUMAN	Decreases Expression	[5]
Protein sprouty homolog 2 (SPRY2)	OTH0CRCZ	SPY2_HUMAN	Decreases Expression	[5]
Leupaxin (LPXN)	OTUNV3CK	LPXN_HUMAN	Decreases Expression	[5]
PR domain zinc finger protein 1 (PRDM1)	OTQLSVBS	PRDM1_HUMAN	Decreases Expression	[5]
Tumor necrosis factor ligand superfamily member 15 (TNFSF15)	OTNGA2BW	TNF15_HUMAN	Decreases Expression	[5]
Integrin beta-like protein 1 (ITGBL1)	OTJDHE17	ITGBL_HUMAN	Decreases Expression	[5]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[5]
Glycophorin-C (GYPC)	OTOEDR7O	GLPC_HUMAN	Decreases Expression	[5]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[5]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[5]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Expression	[5]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Decreases Expression	[5]
Pentraxin-related protein PTX3 (PTX3)	OTPXHRKU	PTX3_HUMAN	Decreases Expression	[5]
5-hydroxytryptamine receptor 7 (HTR7)	OT44DEWB	5HT7R_HUMAN	Decreases Expression	[5]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[5]
ETS translocation variant 5 (ETV5)	OTE2OBM4	ETV5_HUMAN	Decreases Expression	[5]
ETS translocation variant 4 (ETV4)	OT8C98UZ	ETV4_HUMAN	Decreases Expression	[5]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[5]
ETS translocation variant 1 (ETV1)	OT6PMJIK	ETV1_HUMAN	Decreases Expression	[5]
Paired mesoderm homeobox protein 1 (PRRX1)	OTTZK5G8	PRRX1_HUMAN	Decreases Expression	[5]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Decreases Expression	[5]
Forkhead box protein G1 (FOXG1)	OTAW57J4	FOXG1_HUMAN	Decreases Expression	[5]
ADP-ribosylation factor-like protein 4C (ARL4C)	OTQ3QNNU	ARL4C_HUMAN	Decreases Expression	[5]
Reelin (RELN)	OTLKMW1O	RELN_HUMAN	Decreases Expression	[5]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[5]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Decreases Expression	[5]
Dual specificity protein phosphatase 4 (DUSP4)	OT6WAO12	DUS4_HUMAN	Decreases Expression	[5]
Monocyte to macrophage differentiation factor (MMD)	OTB5I4OC	PAQRB_HUMAN	Decreases Expression	[5]
Syntaxin-1A (STX1A)	OTSBUZB4	STX1A_HUMAN	Decreases Expression	[5]
Dual specificity protein phosphatase 6 (DUSP6)	OT4H6RKW	DUS6_HUMAN	Decreases Expression	[5]
Kinesin-like protein KIF24 (KIF24)	OTJTA5V3	KIF24_HUMAN	Decreases Expression	[5]
Anoctamin-1 (ANO1)	OTSREUNI	ANO1_HUMAN	Decreases Expression	[5]
NADH-cytochrome b5 reductase 2 (CYB5R2)	OTTLM7XN	NB5R2_HUMAN	Decreases Expression	[5]
Dynamin-binding protein (DNMBP)	OTMHH14H	DNMBP_HUMAN	Decreases Expression	[5]
Sialic acid-binding Ig-like lectin 15 (SIGLEC15)	OTON4K9S	SIG15_HUMAN	Decreases Expression	[5]
UPF0606 protein KIAA1549L (KIAA1549L)	OT80HUVY	K154L_HUMAN	Decreases Expression	[5]
Neuron navigator 3 (NAV3)	OT97M1TR	NAV3_HUMAN	Decreases Expression	[5]
Dedicator of cytokinesis protein 4 (DOCK4)	OTH3XY8B	DOCK4_HUMAN	Decreases Expression	[5]
Transmembrane protein 156 (TMEM156)	OTH7YJID	TM156_HUMAN	Decreases Expression	[5]
Tribbles homolog 2 (TRIB2)	OTHSX3MX	TRIB2_HUMAN	Decreases Expression	[5]
Hyaluronan synthase 2 (HAS2)	OTTD3PAL	HYAS2_HUMAN	Decreases Expression	[5]
Neuronal cell adhesion molecule (NRCAM)	OT80HHQ2	NRCAM_HUMAN	Decreases Expression	[5]
Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2)	OTB71I02	DCBD2_HUMAN	Decreases Expression	[5]
Formin-like protein 2 (FMNL2)	OT9OVWCV	FMNL2_HUMAN	Decreases Expression	[5]
Paternally-expressed gene 3 protein (PEG3)	OTHQW98S	PEG3_HUMAN	Decreases Expression	[5]
Disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)	OTH88TXU	ADA19_HUMAN	Decreases Expression	[5]
Endothelial cell-specific molecule 1 (ESM1)	OT331Y8V	ESM1_HUMAN	Decreases Expression	[5]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_HUMAN	Decreases Expression	[5]
Neurotrimin (NTM)	OTHF0UQU	NTRI_HUMAN	Decreases Expression	[5]
Type 2 lactosamine alpha-2,3-sialyltransferase (ST3GAL6)	OTB17Q43	SIA10_HUMAN	Decreases Expression	[5]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[8]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Expression	[9]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[10]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Decreases Expression	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[12]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[13]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[13]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[14]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Decreases Activity	[15]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[12]
DNA repair endonuclease XPF (ERCC4)	OTFIOPG1	XPF_HUMAN	Increases Expression	[11]

Indication(s) of Gefitinib

Disease Entry	ICD 11	Status	REF
Colon adenocarcinoma	N.A.	Approved	[3]
Glioblastoma	2A00	Approved	[3]
Lung cancer	2C25.0	Approved	[3]
Non-small-cell lung cancer	2C25.Y	Approved	[3]
Rectal adenocarcinoma	2B92	Approved	[3]
Rectum mucinous adenocarcinoma	N.A.	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Head and neck cancer	2D42	Phase 3	[4]
Urethral cancer	2C93	Phase 2	[4]
Colon cancer	2B90.Z	Investigative	[3]
Colon mucinous adenocarcinoma	N.A.	Investigative	[3]

Gefitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[21]

Gefitinib Interacts with 4 DTP Molecule(s)

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

Gefitinib Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[25]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[26]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[25]

Gefitinib Interacts with 64 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	Increases ADR	[27]
Sulfhydryl oxidase 1 (QSOX1)	OT4ZPK4P	QSOX1_HUMAN	Increases Expression	[28]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Decreases Expression	[28]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[28]
Fibroblast growth factor 6 (FGF6)	OTRJ679P	FGF6_HUMAN	Increases Expression	[28]
Ski oncogene (SKI)	OT4KJ8F6	SKI_HUMAN	Increases Expression	[28]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[28]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[28]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[28]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Increases Expression	[28]
Adenosine receptor A1 (ADORA1)	OTI7X39E	AA1R_HUMAN	Decreases Expression	[28]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[28]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Increases Expression	[28]
Epidermal growth factor receptor substrate 15 (EPS15)	OT7NPP8U	EPS15_HUMAN	Increases Expression	[28]
Neural retina-specific leucine zipper protein (NRL)	OT65MFKQ	NRL_HUMAN	Decreases Expression	[28]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2)	OT3JPRCQ	GBB2_HUMAN	Decreases Expression	[28]
Retinal guanylyl cyclase 1 (GUCY2D)	OT81UJI0	GUC2D_HUMAN	Decreases Expression	[28]
Cell growth regulator with RING finger domain protein 1 (CGRRF1)	OTLMNRCL	CGRF1_HUMAN	Increases Expression	[28]
Dual specificity protein phosphatase 9 (DUSP9)	OTZZWEQL	DUS9_HUMAN	Decreases Expression	[28]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[29]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[30]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[31]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[32]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[33]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Phosphorylation	[34]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)	OTZE5Q7R	DOA_HUMAN	Affects Expression	[35]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases Secretion	[36]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[37]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[38]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Increases Secretion	[36]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[39]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[39]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[40]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Affects Expression	[35]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[31]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[33]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Decreases Phosphorylation	[17]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[40]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Response To Substance	[41]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[37]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[42]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Increases Expression	[43]
MHC class I polypeptide-related sequence B (MICB)	OTS2DVDW	MICB_HUMAN	Increases Expression	[44]
MHC class I polypeptide-related sequence A (MICA)	OTPEIEAR	MICA_HUMAN	Increases Expression	[44]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[35]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[32]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[45]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Decreases Response To Substance	[46]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Affects Response To Substance	[47]
Membrane-associated progesterone receptor component 1 (PGRMC1)	OTBE6WAC	PGRC1_HUMAN	Decreases Response To Substance	[48]
RNA-binding protein 7 (RBM7)	OTFIWTMF	RBM7_HUMAN	Affects Response To Substance	[49]
Cell death regulator Aven (AVEN)	OTGIN5YK	AVEN_HUMAN	Affects Response To Substance	[49]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Response To Substance	[50]
Phospholipase B-like 1 (PLBD1)	OTHYEB4W	PLBL1_HUMAN	Affects Response To Substance	[49]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Response To Substance	[37]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Affects Response To Substance	[49]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Affects Response To Substance	[20]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[51]
Ceramide transfer protein (CERT1)	OTNUCNHX	CERT_HUMAN	Affects Response To Substance	[49]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[49]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[52]
Pericentrin (PCNT)	OTW4Z65J	PCNT_HUMAN	Decreases Response To Substance	[48]
Coronin-1C (CORO1C)	OTXDF9T3	COR1C_HUMAN	Affects Response To Substance	[49]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Affects Response To Substance	[20]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Diffuse intrinsic pontine glioma	DCCCPG1	SU-DIPG-XIII	Investigative	[1]

References

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