Details of the Drug Combination

General Information of Drug Combination (ID: DCEND54)

• Drug Combination Name: Pramipexole + Ursodeoxycholic acid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pramipexole (DMNMW9R): Small molecular drug
  Ursodeoxycholic acid (DMCUT21): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.93
  Bliss Independence Score: 0.93
  Loewe Additivity Score: 15.06
  LHighest Single Agent (HSA) Score: 15.06

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pramipexole

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[2]

Pramipexole Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Modulator	[7]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Modulator	[7]

Pramipexole Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[8]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[9]

Indication(s) of Ursodeoxycholic acid

Disease Entry	ICD 11	Status	REF
Cholelithiasis	DC11	Approved	[3]
Primary biliary cholangitis	DB96.1	Approved	[4]
Primary biliary cirrhosis	DB96.1	Approved	[5]
Colon cancer	2B90.Z	Investigative	[6]

Ursodeoxycholic acid Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 23 member 2 (SLC23A2)	TTOP832	S23A2_HUMAN	Activator	[12]
Biliverdin reductase A (BLVRA)	TTJBPN3	BIEA_HUMAN	Activator	[12]

Ursodeoxycholic acid Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[13]

Ursodeoxycholic acid Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-hydroxysteroid dehydrogenase (hdhB)	DEOMLHG	A4ECA9_9ACTN	Metabolism	[14]

Ursodeoxycholic acid Interacts with 69 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Increases Uptake	[13]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[15]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[15]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[15]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[16]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[17]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[17]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[18]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[19]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28)	OTRBREQ9	ANR28_HUMAN	Affects Expression	[10]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[20]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Increases Expression	[21]
Splicing factor 3B subunit 1 (SF3B1)	OTNTX2DG	SF3B1_HUMAN	Affects Expression	[10]
Rho-related BTB domain-containing protein 3 (RHOBTB3)	OT1BFKPH	RHBT3_HUMAN	Affects Expression	[10]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[22]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)	OT7KZMP2	DRA_HUMAN	Increases Expression	[23]
Fibrinogen gamma chain (FGG)	OT5BJSEX	FIBG_HUMAN	Affects Expression	[10]
C4b-binding protein alpha chain (C4BPA)	OTHNH6Y8	C4BPA_HUMAN	Affects Expression	[10]
ADP/ATP translocase 2 (SLC25A5)	OT1XIBMN	ADT2_HUMAN	Affects Expression	[10]
Large ribosomal subunit protein P2 (RPLP2)	OT2YBK3W	RLA2_HUMAN	Affects Expression	[10]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[24]
Involucrin (IVL)	OT4VPNGY	INVO_HUMAN	Decreases Expression	[25]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Increases Expression	[18]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)	OTB8HCED	CN37_HUMAN	Affects Expression	[10]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[19]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT)	OT9LBJVN	ODP2_HUMAN	Affects Expression	[10]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[18]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Decreases Expression	[18]
Large ribosomal subunit protein eL33 (RPL35A)	OTDDJUWF	RL35A_HUMAN	Affects Expression	[10]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Decreases Expression	[18]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Expression	[10]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[18]
Large ribosomal subunit protein uL16 (RPL10)	OTBHOZGC	RL10_HUMAN	Affects Expression	[10]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[18]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[24]
Intercellular adhesion molecule 3 (ICAM3)	OTTZ5A5D	ICAM3_HUMAN	Affects Expression	[10]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Affects Expression	[10]
Eukaryotic translation initiation factor 1 (EIF1)	OTB4GZ0V	EIF1_HUMAN	Affects Expression	[10]
T-complex protein 1 subunit epsilon (CCT5)	OTPZ38BT	TCPE_HUMAN	Affects Expression	[10]
T-complex protein 1 subunit gamma (CCT3)	OTL6EOS1	TCPG_HUMAN	Affects Expression	[10]
Gastrotropin (FABP6)	OTIRQWLW	FABP6_HUMAN	Increases Expression	[26]
Small ribosomal subunit protein mS29 (DAP3)	OTNPEZYM	RT29_HUMAN	Affects Expression	[10]
Nucleosome assembly protein 1-like 1 (NAP1L1)	OTI7WBZV	NP1L1_HUMAN	Affects Expression	[10]
Large ribosomal subunit protein eL27 (RPL27)	OTWEOUTX	RL27_HUMAN	Affects Expression	[10]
Small ribosomal subunit protein uS15 (RPS13)	OTOMDIJ2	RS13_HUMAN	Affects Expression	[10]
Small ribosomal subunit protein eS28 (RPS28)	OT12IES1	RS28_HUMAN	Affects Expression	[10]
Large ribosomal subunit protein eL32 (RPL32)	OTKRQJT4	RL32_HUMAN	Affects Expression	[10]
Large ribosomal subunit protein eL6 (RPL6)	OTRU71O4	RL6_HUMAN	Affects Expression	[10]
Single-stranded DNA-binding protein, mitochondrial (SSBP1)	OTH2PZWH	SSBP_HUMAN	Affects Expression	[10]
ATP-dependent RNA helicase A (DHX9)	OT5AAOQI	DHX9_HUMAN	Affects Expression	[10]
Fibrinogen-like protein 1 (FGL1)	OTT0QHQ1	FGL1_HUMAN	Affects Expression	[10]
Serine/threonine-protein kinase 3 (STK3)	OTLNSCQD	STK3_HUMAN	Affects Expression	[10]
DnaJ homolog subfamily C member 3 (DNAJC3)	OT7ROIJF	DNJC3_HUMAN	Decreases Expression	[18]
Protein Smaug homolog 2 (SAMD4B)	OTVRZJ5D	SMAG2_HUMAN	Affects Expression	[10]
Ribosomal protein eS27-like (RPS27L)	OTZWHU0N	RS27L_HUMAN	Affects Expression	[10]
Endoplasmic reticulum metallopeptidase 1 (ERMP1)	OT9CIEO2	ERMP1_HUMAN	Affects Expression	[10]
E3 ubiquitin-protein ligase RBBP6 (RBBP6)	OTTVG4HU	RBBP6_HUMAN	Affects Expression	[10]
Out at first protein homolog (OAF)	OTOR9CR5	OAF_HUMAN	Affects Expression	[10]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[20]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[20]
Shieldin complex subunit 2 (SHLD2)	OTMLERXL	SHLD2_HUMAN	Affects Expression	[10]
E3 ubiquitin-protein ligase rififylin (RFFL)	OT85MGDH	RFFL_HUMAN	Affects Expression	[10]
AP-2 complex subunit mu (AP2M1)	OTQCOSFN	AP2M1_HUMAN	Affects Expression	[10]
Ribosomal protein eL39-like 2 (RPL39L)	OTAV1MJQ	RL39L_HUMAN	Affects Expression	[10]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Increases Expression	[27]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[18]
Protein sprouty homolog 4 (SPRY4)	OT2VK9N0	SPY4_HUMAN	Affects Expression	[10]
Soluble lamin-associated protein of 75 kDa (FAM169A)	OT2FDMA1	F169A_HUMAN	Affects Expression	[10]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[13]

References

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• [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: 7104).
• [6] Design and synthesis of bile acid derivatives and their activity against colon cancer. RSC Med Chem. 2022 Aug 19;13(11):1391-1409.
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• [13] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [14] Identification, cloning, heterologous expression, and characterization of a NADPH-dependent 7beta-hydroxysteroid dehydrogenase from Collinsella aerofaciens. Appl Microbiol Biotechnol. 2011 Apr;90(1):127-35.
• [15] Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
• [16] Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Clin Pharmacol Ther. 2006 May;79(5):449-60.
• [17] Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy. Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
• [18] Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes. PLoS One. 2013 Dec 3;8(12):e82086. doi: 10.1371/journal.pone.0082086. eCollection 2013.
• [19] Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. Carcinogenesis. 2011 May;32(5):723-31. doi: 10.1093/carcin/bgr038. Epub 2011 Feb 28.
• [20] Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
• [21] The synthetic bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide suppresses TNF-induced liver injury. J Hepatol. 2011 Apr;54(4):674-84. doi: 10.1016/j.jhep.2010.07.028. Epub 2010 Sep 27.
• [22] The farnesoid X receptor controls gene expression in a ligand- and promoter-selective fashion. J Biol Chem. 2004 Mar 5;279(10):8856-61. doi: 10.1074/jbc.M306422200. Epub 2003 Dec 18.
• [23] Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of IFN-gamma-induced MHC class II gene expression via a glucocorticoid receptor-dependent pathway. J Immunol. 1996 Feb 15;156(4):1601-8.
• [24] Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines. World J Gastroenterol. 2007 Mar 21;13(11):1652-8. doi: 10.3748/wjg.v13.i11.1652.
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