Details of the Drug Combination

General Information of Drug Combination (ID: DC81M9X)

• Drug Combination Name: Pazopanib + Ursodeoxycholic acid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pazopanib (DMF57DM): N.A.
  Ursodeoxycholic acid (DMCUT21): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.43
  Bliss Independence Score: 6.43
  Loewe Additivity Score: 18.39
  LHighest Single Agent (HSA) Score: 18.39

Molecular Interaction Atlas of This Drug Combination

Pazopanib Interacts with 4 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	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]

Pazopanib Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[9]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Expression	[9]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[10]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Increases Expression	[9]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Secretion	[11]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[12]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[13]
Myeloblastin (PRTN3)	OT72MHP7	PRTN3_HUMAN	Increases Expression	[11]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[14]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[14]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[12]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Increases ADR	[15]

Indication(s) of Ursodeoxycholic acid

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

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	[18]
Biliverdin reductase A (BLVRA)	TTJBPN3	BIEA_HUMAN	Activator	[18]

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	[19]

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	[20]

Ursodeoxycholic acid Interacts with 104 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	[19]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[21]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[21]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[21]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[22]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[22]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[23]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[23]
Solute carrier family 23 member 2 (SLC23A2)	OTJ5CQMA	S23A2_HUMAN	Increases Expression	[23]
Solute carrier family 23 member 1 (SLC23A1)	OTE6F9U6	S23A1_HUMAN	Increases Expression	[23]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[24]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[25]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28)	OTRBREQ9	ANR28_HUMAN	Affects Expression	[16]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[26]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Increases Expression	[27]
Splicing factor 3B subunit 1 (SF3B1)	OTNTX2DG	SF3B1_HUMAN	Affects Expression	[16]
Rho-related BTB domain-containing protein 3 (RHOBTB3)	OT1BFKPH	RHBT3_HUMAN	Affects Expression	[16]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[28]
Fibroblast growth factor 19 (FGF19)	OT2DVJWY	FGF19_HUMAN	Increases Expression	[26]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)	OT7KZMP2	DRA_HUMAN	Increases Expression	[29]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[30]
Fibrinogen gamma chain (FGG)	OT5BJSEX	FIBG_HUMAN	Affects Expression	[16]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Affects Expression	[16]
C4b-binding protein alpha chain (C4BPA)	OTHNH6Y8	C4BPA_HUMAN	Affects Expression	[16]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Localization	[31]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Ubiquitination	[32]
ADP/ATP translocase 2 (SLC25A5)	OT1XIBMN	ADT2_HUMAN	Affects Expression	[16]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[33]
Large ribosomal subunit protein P2 (RPLP2)	OT2YBK3W	RLA2_HUMAN	Affects Expression	[16]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Increases Activity	[34]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[35]
Involucrin (IVL)	OT4VPNGY	INVO_HUMAN	Decreases Expression	[36]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Increases Expression	[24]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)	OTB8HCED	CN37_HUMAN	Affects Expression	[16]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[25]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[35]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT)	OT9LBJVN	ODP2_HUMAN	Affects Expression	[16]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[24]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Affects Expression	[16]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[24]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Decreases Expression	[24]
Large ribosomal subunit protein eL33 (RPL35A)	OTDDJUWF	RL35A_HUMAN	Affects Expression	[16]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Decreases Expression	[24]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Expression	[16]
Endothelin-2 (EDN2)	OTQ7RCPI	EDN2_HUMAN	Decreases Expression	[37]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[28]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[35]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[24]
Large ribosomal subunit protein uL16 (RPL10)	OTBHOZGC	RL10_HUMAN	Affects Expression	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[24]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[35]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[38]
Intercellular adhesion molecule 3 (ICAM3)	OTTZ5A5D	ICAM3_HUMAN	Affects Expression	[16]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[24]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Affects Expression	[16]
Eukaryotic translation initiation factor 1 (EIF1)	OTB4GZ0V	EIF1_HUMAN	Affects Expression	[16]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[38]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[38]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[38]
T-complex protein 1 subunit epsilon (CCT5)	OTPZ38BT	TCPE_HUMAN	Affects Expression	[16]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[24]
T-complex protein 1 subunit gamma (CCT3)	OTL6EOS1	TCPG_HUMAN	Affects Expression	[16]
Gastrotropin (FABP6)	OTIRQWLW	FABP6_HUMAN	Increases Expression	[39]
Small ribosomal subunit protein mS29 (DAP3)	OTNPEZYM	RT29_HUMAN	Affects Expression	[16]
Exportin-2 (CSE1L)	OTV2X99A	XPO2_HUMAN	Affects Expression	[16]
Nucleosome assembly protein 1-like 1 (NAP1L1)	OTI7WBZV	NP1L1_HUMAN	Affects Expression	[16]
Large ribosomal subunit protein eL27 (RPL27)	OTWEOUTX	RL27_HUMAN	Affects Expression	[16]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Activity	[40]
Small ribosomal subunit protein uS15 (RPS13)	OTOMDIJ2	RS13_HUMAN	Affects Expression	[16]
Small ribosomal subunit protein eS28 (RPS28)	OT12IES1	RS28_HUMAN	Affects Expression	[16]
Large ribosomal subunit protein eL32 (RPL32)	OTKRQJT4	RL32_HUMAN	Affects Expression	[16]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Affects Expression	[16]
Large ribosomal subunit protein eL6 (RPL6)	OTRU71O4	RL6_HUMAN	Affects Expression	[16]
Single-stranded DNA-binding protein, mitochondrial (SSBP1)	OTH2PZWH	SSBP_HUMAN	Affects Expression	[16]
Protein kinase C delta type (PRKCD)	OTSEH90E	KPCD_HUMAN	Increases Localization	[25]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[35]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[27]
ATP-dependent RNA helicase A (DHX9)	OT5AAOQI	DHX9_HUMAN	Affects Expression	[16]
Fibrinogen-like protein 1 (FGL1)	OTT0QHQ1	FGL1_HUMAN	Affects Expression	[16]
Serine/threonine-protein kinase 3 (STK3)	OTLNSCQD	STK3_HUMAN	Affects Expression	[16]
DnaJ homolog subfamily C member 3 (DNAJC3)	OT7ROIJF	DNJC3_HUMAN	Decreases Expression	[24]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[25]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Localization	[38]
Protein Smaug homolog 2 (SAMD4B)	OTVRZJ5D	SMAG2_HUMAN	Affects Expression	[16]
Chondroitin sulfate proteoglycan 4 (CSPG4)	OTW2D6DE	CSPG4_HUMAN	Affects Expression	[16]
Ribosomal protein eS27-like (RPS27L)	OTZWHU0N	RS27L_HUMAN	Affects Expression	[16]
Endoplasmic reticulum metallopeptidase 1 (ERMP1)	OT9CIEO2	ERMP1_HUMAN	Affects Expression	[16]
E3 ubiquitin-protein ligase RBBP6 (RBBP6)	OTTVG4HU	RBBP6_HUMAN	Affects Expression	[16]
Out at first protein homolog (OAF)	OTOR9CR5	OAF_HUMAN	Affects Expression	[16]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[26]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[26]
Shieldin complex subunit 2 (SHLD2)	OTMLERXL	SHLD2_HUMAN	Affects Expression	[16]
G-protein coupled bile acid receptor 1 (GPBAR1)	OT4BKEJ9	GPBAR_HUMAN	Decreases Expression	[24]
E3 ubiquitin-protein ligase rififylin (RFFL)	OT85MGDH	RFFL_HUMAN	Affects Expression	[16]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[41]
AP-2 complex subunit mu (AP2M1)	OTQCOSFN	AP2M1_HUMAN	Affects Expression	[16]
Ribosomal protein eL39-like 2 (RPL39L)	OTAV1MJQ	RL39L_HUMAN	Affects Expression	[16]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Increases Expression	[40]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[24]
Protein sprouty homolog 4 (SPRY4)	OT2VK9N0	SPY4_HUMAN	Affects Expression	[16]
Endosialin (CD248)	OTEBWORQ	CD248_HUMAN	Affects Expression	[16]
Soluble lamin-associated protein of 75 kDa (FAM169A)	OT2FDMA1	F169A_HUMAN	Affects Expression	[16]
Sulfotransferase 2A1 (SULT2A1)	OT0ISKQ4	ST2A1_HUMAN	Increases Sulfation	[42]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[19]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Management of symptomatic cholelithiasis: a systematic review. Syst Rev. 2022 Dec 12;11(1):267.
• [3] Primary biliary cholangitis: pathogenesis and therapeutic opportunities. Nat Rev Gastroenterol Hepatol. 2020 Feb;17(2):93-110.
• [4] 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).
• [5] Design and synthesis of bile acid derivatives and their activity against colon cancer. RSC Med Chem. 2022 Aug 19;13(11):1391-1409.
• [6] Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.
• [7] Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35.
• [8] Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54.
• [9] Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch Toxicol. 2018 Apr;92(4):1435-1451.
• [10] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
• [11] Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
• [12] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [13] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [14] MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.
• [15] HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. Clin Cancer Res. 2016 Mar 15;22(6):1371-7. doi: 10.1158/1078-0432.CCR-15-2044. Epub 2015 Nov 6.
• [16] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [17] UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3. Chem Biol Interact. 2019 Sep 1;310:108745. doi: 10.1016/j.cbi.2019.108745. Epub 2019 Jul 9.
• [18] Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal... Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
• [19] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [20] 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.
• [21] 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.
• [22] Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans. Clin Pharmacol Ther. 2006 May;79(5):449-60.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] Hepatic apolipoprotein A-I gene expression in patients with cholesterol gallstones treated with ursodeoxycholic acid. Ann Hepatol. 2002 Apr-Jun;1(2):85-9.
• [31] Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Invest. 2008 Feb;118(2):695-709. doi: 10.1172/JCI33156.
• [32] Ursodeoxycholic acid modulates the ubiquitin-proteasome degradation pathway of p53. Biochem Biophys Res Commun. 2010 Oct 1;400(4):649-54. doi: 10.1016/j.bbrc.2010.08.121. Epub 2010 Aug 31.
• [33] Ursodeoxycholic acid inhibits endothelin-1 production in human vascular endothelial cells. Eur J Pharmacol. 2004 Nov 28;505(1-3):67-74. doi: 10.1016/j.ejphar.2004.10.042.
• [34] Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids. Int J Cancer. 1995 Mar 29;61(1):35-9. doi: 10.1002/ijc.2910610107.
• [35] 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.
• [36] Correlation of chemopreventive efficacy data from the human epidermal cell assay with in vivo data. Anticancer Res. 2000 Jan-Feb;20(1A):27-32.
• [37] Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis. Aliment Pharmacol Ther. 2005 Feb 1;21(3):227-34. doi: 10.1111/j.1365-2036.2005.02307.x.
• [38] Ursodeoxycholic acid induces glutathione synthesis through activation of PI3K/Akt pathway in HepG2 cells. Biochem Pharmacol. 2009 Mar 1;77(5):858-66. doi: 10.1016/j.bcp.2008.11.012. Epub 2008 Nov 25.
• [39] Regulation of ileal bile acid-binding protein expression in Caco-2 cells by ursodeoxycholic acid: role of the farnesoid X receptor. Biochem Pharmacol. 2005 Jun 15;69(12):1755-63. doi: 10.1016/j.bcp.2005.03.019.
• [40] Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011 Jun;25(6):1739-46. doi: 10.3892/or.2011.1239. Epub 2011 Mar 29.
• [41] Chemiluminescence quantitative immunohistochemical determination of MRP2 in liver biopsies. J Histochem Cytochem. 2005 Dec;53(12):1451-7. doi: 10.1369/jhc.5A6621.2005. Epub 2005 Jun 13.
• [42] Kinetic analysis of bile acid sulfation by stably expressed human sulfotransferase 2A1 (SULT2A1). Xenobiotica. 2010 Mar;40(3):184-94.