Details of the Drug Combination

General Information of Drug Combination (ID: DCI7LTA)

• Drug Combination Name: Zileuton + Probenecid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Zileuton (DMVRIC2): Small molecular drug
  Probenecid (DMMFWOJ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 31.17
  Bliss Independence Score: 31.17
  Loewe Additivity Score: 45.9
  LHighest Single Agent (HSA) Score: 45.92

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Zileuton

Disease Entry	ICD 11	Status	REF
Allergic asthma	CA23.0	Approved	[2]
Asthma	CA23	Approved	[3]
Intrinsic asthma	N.A.	Approved	[2]

Zileuton Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[6]

Zileuton Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[7]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[7]

Zileuton Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[10]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[11]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Decreases Activity	[12]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Increases Activity	[12]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[13]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[14]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[14]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Affects Response To Substance	[15]

Indication(s) of Probenecid

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[4]
Gout	FA25	Approved	[5]
Hyperuricaemia	5C55.Y	Approved	[5]

Probenecid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 22 member 8 (SLC22A8)	TTTQR47	S22A8_HUMAN	Blocker	[17]

Probenecid Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[18]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[19]
Monocarboxylate transporter 6 (SLC16A5)	DT3I124	MOT6_HUMAN	Substrate	[20]

Probenecid Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[21]

Probenecid Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Activity	[22]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[23]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[24]
Taste receptor type 2 member 38 (TAS2R38)	OTX5MM36	T2R38_HUMAN	Decreases Activity	[25]
Taste receptor type 2 member 43 (TAS2R43)	OT70V8MZ	T2R43_HUMAN	Decreases Activity	[25]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[26]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[26]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[27]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[27]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8)	OTA0WELF	SC5A8_HUMAN	Decreases Activity	[28]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Decreases Expression	[29]
Solute carrier family 22 member 12 (SLC22A12)	OT72ZAWS	S22AC_HUMAN	Affects Activity	[30]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[31]

References

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• [4] Probenecid FDA Label
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