Details of the Drug Combination

General Information of Drug Combination (ID: DCLJ3AG)

• Drug Combination Name: Gefitinib + Sirolimus
• Indication: Melanoma; Status: Investigative [1]
• Component Drugs:
  Gefitinib (DM15F0X): Small molecular drug
  Sirolimus (DMGW1ID): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MALME-3M
  Zero Interaction Potency (ZIP) Score: 2.01
  Bliss Independence Score: 1.99
  Loewe Additivity Score: 5.07
  LHighest Single Agent (HSA) Score: 5.64

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Gefitinib

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

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	[15]

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	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[18]

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	[19]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[20]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]

Gefitinib Interacts with 103 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	[21]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[22]
Sulfhydryl oxidase 1 (QSOX1)	OT4ZPK4P	QSOX1_HUMAN	Increases Expression	[23]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Decreases Expression	[23]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[23]
Fibroblast growth factor 6 (FGF6)	OTRJ679P	FGF6_HUMAN	Increases Expression	[23]
Ski oncogene (SKI)	OT4KJ8F6	SKI_HUMAN	Increases Expression	[23]
Erythropoietin receptor (EPOR)	OTUIOEU3	EPOR_HUMAN	Increases Expression	[23]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[23]
Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B)	OTDS2EAR	TNR1B_HUMAN	Decreases Expression	[23]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[23]
Cytochrome P450 2F1 (CYP2F1)	OTY3HJH1	CP2F1_HUMAN	Decreases Expression	[23]
Replication protein A 70 kDa DNA-binding subunit (RPA1)	OT76POLP	RFA1_HUMAN	Increases Expression	[23]
Adenosine receptor A1 (ADORA1)	OTI7X39E	AA1R_HUMAN	Decreases Expression	[23]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Decreases Expression	[23]
DNA mismatch repair protein Mlh1 (MLH1)	OTG5XDD8	MLH1_HUMAN	Decreases Expression	[23]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Increases Expression	[23]
Epidermal growth factor receptor substrate 15 (EPS15)	OT7NPP8U	EPS15_HUMAN	Increases Expression	[23]
Neuronal pentraxin-2 (NPTX2)	OT3SSJDP	NPTX2_HUMAN	Decreases Expression	[23]
Leptin receptor (LEPR)	OT9H7G0C	LEPR_HUMAN	Decreases Expression	[23]
Neural retina-specific leucine zipper protein (NRL)	OT65MFKQ	NRL_HUMAN	Decreases Expression	[23]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2)	OT3JPRCQ	GBB2_HUMAN	Decreases Expression	[23]
Retinal guanylyl cyclase 1 (GUCY2D)	OT81UJI0	GUC2D_HUMAN	Decreases Expression	[23]
Cell growth regulator with RING finger domain protein 1 (CGRRF1)	OTLMNRCL	CGRF1_HUMAN	Increases Expression	[23]
Dual specificity protein phosphatase 9 (DUSP9)	OTZZWEQL	DUS9_HUMAN	Decreases Expression	[23]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[24]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[25]
Glycogen synthase kinase-3 beta (GSK3B)	OTL3L14B	GSK3B_HUMAN	Decreases Expression	[25]
Cyclin-dependent kinase 6 (CDK6)	OTR95N0X	CDK6_HUMAN	Decreases Expression	[25]
Telomerase reverse transcriptase (TERT)	OT085VVA	TERT_HUMAN	Decreases Expression	[26]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[27]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[28]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[29]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[11]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[30]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Expression	[31]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Phosphorylation	[32]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Phosphorylation	[33]
HLA class II histocompatibility antigen, DO alpha chain (HLA-DOA)	OTZE5Q7R	DOA_HUMAN	Affects Expression	[31]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases Secretion	[30]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Increases Phosphorylation	[34]
High mobility group protein B1 (HMGB1)	OT4B7CPF	HMGB1_HUMAN	Increases Secretion	[30]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[35]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Increases Secretion	[30]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[36]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[11]
Platelet endothelial cell adhesion molecule (PECAM1)	OTXOM4D9	PECA1_HUMAN	Decreases Expression	[11]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Decreases Phosphorylation	[28]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[37]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[22]
DnaJ homolog subfamily B member 1 (DNAJB1)	OTCOSEVH	DNJB1_HUMAN	Increases Secretion	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[38]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[38]
Caspase-1 (CASP1)	OTZ3YQFU	CASP1_HUMAN	Increases Activity	[30]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[22]
HLA class I histocompatibility antigen, alpha chain F (HLA-F)	OT76CM19	HLAF_HUMAN	Affects Expression	[31]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[39]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[27]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Phosphorylation	[28]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[29]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Decreases Phosphorylation	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[22]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Response To Substance	[40]
Cytochrome c (CYCS)	OTBFALJD	CYC_HUMAN	Affects Localization	[35]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Decreases Expression	[26]
Caveolin-1 (CAV1)	OTEZUR1L	CAV1_HUMAN	Increases Expression	[38]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[41]
Kelch-like ECH-associated protein 1 (KEAP1)	OTFHOD0C	KEAP1_HUMAN	Increases Expression	[42]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[40]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[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]
Estrogen receptor beta (ESR2)	OTXNR2WQ	ESR2_HUMAN	Increases Expression	[45]
Serine protease HTRA1 (HTRA1)	OTR8ACBF	HTRA1_HUMAN	Increases Expression	[46]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[31]
Autophagy protein 5 (ATG5)	OT4T5SMS	ATG5_HUMAN	Increases Expression	[28]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[47]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Decreases Response To Substance	[48]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[49]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Affects Response To Substance	[50]
Membrane-associated progesterone receptor component 1 (PGRMC1)	OTBE6WAC	PGRC1_HUMAN	Decreases Response To Substance	[51]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Response To Substance	[52]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Affects Response To Substance	[53]
RNA-binding protein 7 (RBM7)	OTFIWTMF	RBM7_HUMAN	Affects Response To Substance	[53]
Cell death regulator Aven (AVEN)	OTGIN5YK	AVEN_HUMAN	Affects Response To Substance	[53]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Response To Substance	[54]
Phospholipase B-like 1 (PLBD1)	OTHYEB4W	PLBL1_HUMAN	Affects Response To Substance	[53]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Response To Substance	[55]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Response To Substance	[35]
Amphiregulin (AREG)	OTJFOR67	AREG_HUMAN	Decreases Response To Substance	[53]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Affects Response To Substance	[53]
Aurora kinase A (AURKA)	OTMX0HYT	AURKA_HUMAN	Decreases Response To Substance	[55]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Affects Response To Substance	[14]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Response To Substance	[56]
Ceramide transfer protein (CERT1)	OTNUCNHX	CERT_HUMAN	Affects Response To Substance	[53]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Affects Response To Substance	[57]
Oncostatin-M-specific receptor subunit beta (OSMR)	OTORWHPL	OSMR_HUMAN	Affects Response To Substance	[53]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Decreases Response To Substance	[58]
Dual specificity protein phosphatase 3 (DUSP3)	OTPJX9B4	DUS3_HUMAN	Affects Response To Substance	[53]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[55]
Pericentrin (PCNT)	OTW4Z65J	PCNT_HUMAN	Decreases Response To Substance	[51]
Coronin-1C (CORO1C)	OTXDF9T3	COR1C_HUMAN	Affects Response To Substance	[53]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Affects Response To Substance	[14]

Indication(s) of Sirolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[4]
Brainstem neoplasm	N.A.	Approved	[4]
Graft-versus-host disease	4B24	Approved	[4]
Intracranial meningioma	N.A.	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Lung lymphangioleiomyomatosis	N.A.	Approved	[4]
Lymphangioleiomyomatosis	CB07	Approved	[5]
Mucosal melanoma	N.A.	Approved	[4]
Multiple myeloma	2A83	Approved	[6]
Multiple sclerosis	8A40	Approved	[4]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Organ transplant rejection	NE84	Approved	[7]
Plasma cell myeloma	2A83.1	Approved	[4]
Prostate cancer	2C82.0	Approved	[4]
Salivary gland squamous cell carcinoma	N.A.	Approved	[4]
Uveitis	9A96.Z	Phase 3	[8]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[9]
Dutch elm disease	8D64	Phase 1/2	[7]
Castration-resistant prostate carcinoma	N.A.	Investigative	[4]
Neuroblastoma	2D11.2	Investigative	[4]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[4]
Polycystic kidney disease	GB8Y	Investigative	[4]
Rheumatoid arthritis	FA20	Investigative	[4]

Sirolimus Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[59]
PI3K/AKT/mTOR pathway (PAm pathway)	TTGQUFK	NOUNIPROTAC	Inhibitor	[60]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[61]

Sirolimus Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[62]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[63]

Sirolimus Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[64]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[65]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[65]

Sirolimus Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Increases ADR	[66]
Calcineurin subunit B type 1 (PPP3R1)	OTGQNFJQ	CANB1_HUMAN	Increases ADR	[66]
Nuclear receptor ROR-gamma (RORC)	OTUBFRPC	RORG_HUMAN	Increases ADR	[66]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCD2KPZ	DU-145	Investigative	[1]
Adenocarcinoma	DCVBPGY	NCIH23	Investigative	[1]
Adult acute myeloid leukemia	DCCIEJ0	HL-60(TB)	Investigative	[1]
Adult T acute lymphoblastic leukemia	DCV7YR5	MOLT-4	Investigative	[1]
Amelanotic melanoma	DC0Z9JC	M14	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCOB0HA	OVCAR-4	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DC31ULJ	IGROV1	Investigative	[1]
Colon adenocarcinoma	DC5ZN0Z	COLO 205	Investigative	[67]

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