Details of the Drug Combination

General Information of Drug Combination (ID: DCEPWMM)

• Drug Combination Name: Mechlorethamine + Nilotinib
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Mechlorethamine (DM0CVXA): Small molecular drug
  Nilotinib (DM7HXWT): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DU-145
  Zero Interaction Potency (ZIP) Score: 3.68
  Bliss Independence Score: 8.57
  Loewe Additivity Score: 1.02
  LHighest Single Agent (HSA) Score: 1.9

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mechlorethamine

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Small lymphocytic lymphoma	2A82.0	Approved	[2]
T-cell lymphoma	2A90	Approved	[3]
Hodgkin lymphoma	2B30	Phase 3	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]

Mechlorethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Intercalator	[8]

Mechlorethamine Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[9]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Activity	[10]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[11]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Activity	[12]
Glutathione S-transferase A2 (GSTA2)	OTW7UB1H	GSTA2_HUMAN	Increases Expression	[13]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[14]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Activity	[12]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[11]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[11]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Stability	[12]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[12]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Expression	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[16]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[14]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[14]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Decreases Expression	[17]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[18]
Transient receptor potential cation channel subfamily A member 1 (TRPA1)	OTRDIR5M	TRPA1_HUMAN	Increases Response To Substance	[19]

Indication(s) of Nilotinib

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[5]

Nilotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Modulator	[23]

Nilotinib Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[24]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[25]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[24]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[26]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[26]

Nilotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[27]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[28]

Nilotinib Interacts with 35 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	Affects Response To Substance	[29]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Response To Substance	[30]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[31]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[31]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[31]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[31]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[21]
Tyrosine-protein kinase ABL1 (ABL1)	OT09YVXH	ABL1_HUMAN	Decreases Phosphorylation	[22]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[22]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Secretion	[32]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[22]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[21]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[33]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[33]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[22]
Breakpoint cluster region protein (BCR)	OTCN76C1	BCR_HUMAN	Decreases Phosphorylation	[34]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[22]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[21]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Decreases Expression	[22]
Histidine decarboxylase (HDC)	OT4WA5YQ	DCHS_HUMAN	Decreases Expression	[35]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[21]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[36]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[21]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[22]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[22]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[22]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[21]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[33]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[21]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[21]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[21]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1)	OTWHN69S	EDEM1_HUMAN	Increases Expression	[22]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[21]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[21]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[21]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Childhood T acute lymphoblastic leukemia	DCDMAD1	CCRF-CEM	Investigative	[37]
Plasma cell myeloma	DCIY505	RPMI-8226	Investigative	[37]
Invasive ductal carcinoma	DCONJZR	T-47D	Investigative	[38]
Adenocarcinoma	DCBI7G4	HCT-15	Investigative	[1]
Adenocarcinoma	DCBTEH5	HCC-2998	Investigative	[1]

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