Details of the Drug Combination

General Information of Drug Combination (ID: DCBMJJQ)

• Drug Combination Name: Probenecid + Tiagabine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Probenecid (DMMFWOJ): Small molecular drug
  Tiagabine (DMKSQG0): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 9.38
  Bliss Independence Score: 9.38
  Loewe Additivity Score: 11.32
  LHighest Single Agent (HSA) Score: 11.37

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Probenecid

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[2]
Gout	FA25	Approved	[3]
Hyperuricaemia	5C55.Y	Approved	[3]

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	[6]

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	[7]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[8]
Monocarboxylate transporter 6 (SLC16A5)	DT3I124	MOT6_HUMAN	Substrate	[9]

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	[10]

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	[11]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Activity	[12]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[13]
Taste receptor type 2 member 38 (TAS2R38)	OTX5MM36	T2R38_HUMAN	Decreases Activity	[14]
Taste receptor type 2 member 43 (TAS2R43)	OT70V8MZ	T2R43_HUMAN	Decreases Activity	[14]
Solute carrier family 22 member 6 (SLC22A6)	OTKRCBVM	S22A6_HUMAN	Decreases Activity	[15]
Organic anion transporter 7 (SLC22A9)	OTO4BJCC	S22A9_HUMAN	Decreases Activity	[15]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[16]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[16]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8)	OTA0WELF	SC5A8_HUMAN	Decreases Activity	[17]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Decreases Expression	[18]
Solute carrier family 22 member 12 (SLC22A12)	OT72ZAWS	S22AC_HUMAN	Affects Activity	[19]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Decreases Activity	[20]

Indication(s) of Tiagabine

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[4]
Anxiety disorder	6B00-6B0Z	Phase 2	[4]

Tiagabine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gamma-aminobutyric acid uptake (GABAU)	TTV9MQG	NOUNIPROTAC	Inhibitor	[21]
GABA transporter GAT-1 (SLC6A1)	TTPRKM0	SC6A1_HUMAN	Inhibitor	[22]

Tiagabine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[24]

Tiagabine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[25]
Sodium- and chloride-dependent GABA transporter 1 (SLC6A1)	OTLCJJF3	SC6A1_HUMAN	Decreases Activity	[26]

References

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• [2] Probenecid FDA Label
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• [12] Mercury induces multidrug resistance-associated protein gene through p38 mitogen-activated protein kinase. Toxicol Lett. 2005 Jan 15;155(1):143-50. doi: 10.1016/j.toxlet.2004.09.007.
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