Details of the Drug Combination

General Information of Drug Combination (ID: DC8XYX9)

• Drug Combination Name: Amodiaquine + VR-776
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Amodiaquine (DME4RA8): Small molecular drug
  VR-776 (DMFQWNI): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 30.75
  Bliss Independence Score: 30.75
  Loewe Additivity Score: 45.99
  LHighest Single Agent (HSA) Score: 45.99

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Amodiaquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[3]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[3]

Amodiaquine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histamine N-methyltransferase (HNMT)	TT2B6EV	HNMT_HUMAN	Inhibitor	[5]

Amodiaquine Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[6]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[6]
Glutathione S-transferase mu-4 (GSTM4)	DERQ52Z	GSTM4_HUMAN	Metabolism	[8]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[9]

Amodiaquine Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Activity	[10]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Response To Substance	[11]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[12]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[12]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[12]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[13]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Decreases Expression	[13]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[14]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Affects Phosphorylation	[15]
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Decreases Activity	[15]
Procathepsin L (CTSL)	OTYTUW29	CATL1_HUMAN	Decreases Activity	[15]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Decreases Activity	[15]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[13]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[11]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[13]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Affects Expression	[15]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Affects Expression	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[11]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Decreases Expression	[13]
Transcription factor E2F1 (E2F1)	OTLKYBBC	E2F1_HUMAN	Affects Expression	[15]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[11]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[11]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[13]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Increases Metabolism	[11]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Increases Metabolism	[11]
Myeloperoxidase (MPO)	OTOOXLIN	PERM_HUMAN	Increases ADR	[16]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Metabolism	[11]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[11]
Cytochrome P450 2A13 (CYP2A13)	OTVUDLT3	CP2AD_HUMAN	Increases Metabolism	[11]
Cytochrome P450 2C18 (CYP2C18)	OTY687L9	CP2CI_HUMAN	Increases Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Metabolism	[8]

Indication(s) of VR-776

Disease Entry	ICD 11	Status	REF
Premature ejaculation	HA03.0Z	Discontinued in Phase 1	[4]

VR-776 Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[17]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[18]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[19]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[20]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[21]

References

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