Details of the Drug Combination

General Information of Drug Combination (ID: DCSKRA1)

• Drug Combination Name: Pamidronate + Probenecid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pamidronate (DMB4AVP): Small molecular drug
  Probenecid (DMMFWOJ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.64
  Bliss Independence Score: 2.64
  Loewe Additivity Score: 17.24
  LHighest Single Agent (HSA) Score: 17.24

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pamidronate

Disease Entry	ICD 11	Status	REF
Bone Paget disease	N.A.	Approved	[2]
Hypercalcaemia	5B91.0	Approved	[3]

Pamidronate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Geranyltranstransferase (FDPS)	TTIKWV4	FPPS_HUMAN	Inhibitor	[6]

Pamidronate Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[7]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[7]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Increases Expression	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[7]
Beta-2-microglobulin (B2M)	OTDWN6NX	B2MG_HUMAN	Decreases Expression	[7]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B)	OTQ4W7MT	TR11B_HUMAN	Increases Expression	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[9]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[10]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Cleavage	[12]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[12]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Expression	[12]
Ras-related protein Rap-1A (RAP1A)	OT5RH6TI	RAP1A_HUMAN	Decreases Prenylation	[13]
Rho-associated protein kinase 1 (ROCK1)	OTSXYVW1	ROCK1_HUMAN	Decreases Expression	[12]
Fibroblast growth factor 23 (FGF23)	OTZT523D	FGF23_HUMAN	Decreases Expression	[14]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases 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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• [2] Pamidronate FDA Label
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7259).
• [4] Probenecid FDA Label
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4357).
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