Details of the Drug Combination

General Information of Drug Combination (ID: DCOHFV6)

• Drug Combination Name: Disulfiram + Osimertinib
• Indication: Non-Small Cell Lung Cancer; Status: Phase 2 [1]
• Component Drugs:
  Disulfiram (DMCL2OK): Small molecular drug
  Osimertinib (DMRJLAT): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Disulfiram

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[4]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[4]

Disulfiram Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
MERS-CoV papain-like proteinase (PL-PRO)	TTYJOLE	R1AB_CVEMC (854-2740)	Inhibitor	[4]
Fatty aldehyde dehydrogenase (ALDH3A2)	TTB6UM0	AL3A2_HUMAN	Inhibitor	[8]
COVID-19 papain-like proteinase (PL-PRO)	TTNHMO8	R1AB_SARS2 (819-2763)	Inhibitor	[3]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[4]

Disulfiram Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[11]

Disulfiram Interacts with 73 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Retinaldehyde dehydrogenase 3 (ALDH1A3)	OT1C9NKQ	AL1A3_HUMAN	Increases ADR	[12]
Dopamine beta-hydroxylase (DBH)	OTC6I2SP	DOPO_HUMAN	Decreases Activity	[13]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Decreases Activity	[14]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[15]
Metallothionein-2 (MT2A)	OTHOACHD	MT2_HUMAN	Increases Expression	[16]
Metallothionein-1F (MT1F)	OTZVUYG1	MT1F_HUMAN	Increases Expression	[16]
Metallothionein-1B (MT1B)	OTUA4FFH	MT1B_HUMAN	Increases Expression	[16]
Metallothionein-1G (MT1G)	OTAV1OCR	MT1G_HUMAN	Increases Expression	[16]
DNA replication licensing factor MCM5 (MCM5)	OTAHLB62	MCM5_HUMAN	Decreases Expression	[16]
DNA replication licensing factor MCM2 (MCM2)	OTGGORIQ	MCM2_HUMAN	Decreases Expression	[16]
Metallothionein-1X (MT1X)	OT9AKFVS	MT1X_HUMAN	Increases Expression	[16]
Transcription factor MafG (MAFG)	OTBQFUZH	MAFG_HUMAN	Increases Expression	[7]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Increases Expression	[7]
Transcription factor MafK (MAFK)	OTZJUE4P	MAFK_HUMAN	Increases Expression	[7]
Glutathione reductase, mitochondrial (GSR)	OTM2TUYM	GSHR_HUMAN	Increases Expression	[7]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases Expression	[7]
Ferritin light chain (FTL)	OTYQA8A6	FRIL_HUMAN	Increases Expression	[7]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[7]
Extracellular superoxide dismutase (SOD3)	OTIOZQAB	SODE_HUMAN	Increases Expression	[7]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[7]
Heat shock 70 kDa protein 1A (HSPA1A)	OTKGIE76	HS71A_HUMAN	Increases Expression	[7]
Microsomal glutathione S-transferase 1 (MGST1)	OTGN1KVZ	MGST1_HUMAN	Increases Expression	[7]
Glucose-6-phosphate 1-dehydrogenase (G6PD)	OT300SMK	G6PD_HUMAN	Increases Expression	[7]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Increases Expression	[7]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[7]
Glutathione peroxidase 3 (GPX3)	OT6PK94R	GPX3_HUMAN	Increases Expression	[7]
Ferrochelatase, mitochondrial (FECH)	OTDWEI6C	HEMH_HUMAN	Increases Expression	[7]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Increases Expression	[7]
NADP-dependent malic enzyme (ME1)	OTSVEUQE	MAOX_HUMAN	Increases Expression	[7]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[7]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[7]
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Increases Expression	[7]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Increases Expression	[7]
Prostaglandin reductase 1 (PTGR1)	OTMAR351	PTGR1_HUMAN	Increases Expression	[7]
SPRY domain-containing SOCS box protein 1 (SPSB1)	OTGY26U4	SPSB1_HUMAN	Increases Expression	[7]
Sulfiredoxin-1 (SRXN1)	OTYDBO4L	SRXN1_HUMAN	Increases Expression	[7]
Transcription factor MafF (MAFF)	OT9B7MX0	MAFF_HUMAN	Increases Expression	[7]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Activity	[17]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Decreases Activity	[17]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Decreases Activity	[18]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[19]
Aldehyde dehydrogenase 1A1 (ALDH1A1)	OTCUWZKB	AL1A1_HUMAN	Decreases Expression	[20]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Activity	[21]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[22]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Expression	[22]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[23]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[24]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[25]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[26]
Integrin alpha-M (ITGAM)	OTAG6HWU	ITAM_HUMAN	Increases Expression	[22]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Secretion	[22]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[25]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[27]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Increases Degradation	[28]
Platelet glycoprotein 4 (CD36)	OT5CZWKY	CD36_HUMAN	Decreases Expression	[22]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Increases Expression	[29]
Cystathionine gamma-lyase (CTH)	OTC90LA0	CGL_HUMAN	Increases Expression	[20]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Affects Expression	[22]
C-C chemokine receptor type 2 (CCR2)	OTQ7T10J	CCR2_HUMAN	Increases Expression	[22]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[30]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[26]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[30]
Gasdermin-D (GSDMD)	OTH39BKI	GSDMD_HUMAN	Decreases Cleavage	[31]
Hemoglobin subunit gamma-2 (HBG2)	OT4J48JJ	HBG2_HUMAN	Increases Expression	[32]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[26]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[23]
Scavenger receptor cysteine-rich type 1 protein M130 (CD163)	OT2E32LN	C163A_HUMAN	Decreases Expression	[22]
Metallothionein-1M (MT1M)	OTVT8PLU	MT1M_HUMAN	Increases Expression	[29]
C-type lectin domain family 7 member A (CLEC7A)	OTRTBH27	CLC7A_HUMAN	Increases Expression	[22]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[33]
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)	OTAYZZE6	AL3A1_HUMAN	Increases Metabolism	[34]
Ataxin-3 (ATXN3)	OTJVVGKT	ATX3_HUMAN	Increases Response To Substance	[35]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[36]

Indication(s) of Osimertinib

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[5]
Melanoma	2C30	Phase 3	[6]

Osimertinib 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	[39]

Osimertinib Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[40]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[41]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[38]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[42]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[43]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[43]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[40]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[41]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Decreases Expression	[44]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Decreases Response To Substance	[41]

References

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