Details of the Drug Combination

General Information of Drug Combination (ID: DCIE3ZE)

• Drug Combination Name: Ursodeoxycholic acid + Quinine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Ursodeoxycholic acid (DMCUT21): Small molecular drug
  Quinine (DMSWYF5): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 14.71
  Bliss Independence Score: 14.71
  Loewe Additivity Score: 24.69
  LHighest Single Agent (HSA) Score: 24.69

Molecular Interaction Atlas of This Drug Combination

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	[9]
Biliverdin reductase A (BLVRA)	TTJBPN3	BIEA_HUMAN	Activator	[9]

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	[10]

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	[11]

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	[10]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[12]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[12]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[13]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[13]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[14]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[14]
Solute carrier family 23 member 2 (SLC23A2)	OTJ5CQMA	S23A2_HUMAN	Increases Expression	[14]
Solute carrier family 23 member 1 (SLC23A1)	OTE6F9U6	S23A1_HUMAN	Increases Expression	[14]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Decreases Expression	[15]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[16]
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A (ANKRD28)	OTRBREQ9	ANR28_HUMAN	Affects Expression	[7]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[17]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Increases Expression	[18]
Splicing factor 3B subunit 1 (SF3B1)	OTNTX2DG	SF3B1_HUMAN	Affects Expression	[7]
Rho-related BTB domain-containing protein 3 (RHOBTB3)	OT1BFKPH	RHBT3_HUMAN	Affects Expression	[7]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Increases Expression	[19]
Fibroblast growth factor 19 (FGF19)	OT2DVJWY	FGF19_HUMAN	Increases Expression	[17]
HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)	OT7KZMP2	DRA_HUMAN	Increases Expression	[20]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Increases Expression	[21]
Fibrinogen gamma chain (FGG)	OT5BJSEX	FIBG_HUMAN	Affects Expression	[7]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Affects Expression	[7]
C4b-binding protein alpha chain (C4BPA)	OTHNH6Y8	C4BPA_HUMAN	Affects Expression	[7]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Localization	[22]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Ubiquitination	[23]
ADP/ATP translocase 2 (SLC25A5)	OT1XIBMN	ADT2_HUMAN	Affects Expression	[7]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[24]
Large ribosomal subunit protein P2 (RPLP2)	OT2YBK3W	RLA2_HUMAN	Affects Expression	[7]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Increases Activity	[25]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Expression	[26]
Involucrin (IVL)	OT4VPNGY	INVO_HUMAN	Decreases Expression	[27]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Increases Expression	[15]
2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)	OTB8HCED	CN37_HUMAN	Affects Expression	[7]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[16]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[26]
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial (DLAT)	OT9LBJVN	ODP2_HUMAN	Affects Expression	[7]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[15]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	OTPG0K7E	IMDH2_HUMAN	Affects Expression	[7]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[15]
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Decreases Expression	[15]
Large ribosomal subunit protein eL33 (RPL35A)	OTDDJUWF	RL35A_HUMAN	Affects Expression	[7]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Decreases Expression	[15]
Alpha-1-acid glycoprotein 2 (ORM2)	OTRJGZP8	A1AG2_HUMAN	Affects Expression	[7]
Endothelin-2 (EDN2)	OTQ7RCPI	EDN2_HUMAN	Decreases Expression	[28]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[19]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[26]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[15]
Large ribosomal subunit protein uL16 (RPL10)	OTBHOZGC	RL10_HUMAN	Affects Expression	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[15]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Decreases Expression	[26]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[29]
Intercellular adhesion molecule 3 (ICAM3)	OTTZ5A5D	ICAM3_HUMAN	Affects Expression	[7]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Expression	[15]
Glycine--tRNA ligase (GARS1)	OT5B6R9Y	GARS_HUMAN	Affects Expression	[7]
Eukaryotic translation initiation factor 1 (EIF1)	OTB4GZ0V	EIF1_HUMAN	Affects Expression	[7]
Glutamate--cysteine ligase catalytic subunit (GCLC)	OTESDI4D	GSH1_HUMAN	Increases Expression	[29]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[29]
Glutathione synthetase (GSS)	OTVSBEIW	GSHB_HUMAN	Increases Expression	[29]
T-complex protein 1 subunit epsilon (CCT5)	OTPZ38BT	TCPE_HUMAN	Affects Expression	[7]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Decreases Expression	[15]
T-complex protein 1 subunit gamma (CCT3)	OTL6EOS1	TCPG_HUMAN	Affects Expression	[7]
Gastrotropin (FABP6)	OTIRQWLW	FABP6_HUMAN	Increases Expression	[30]
Small ribosomal subunit protein mS29 (DAP3)	OTNPEZYM	RT29_HUMAN	Affects Expression	[7]
Exportin-2 (CSE1L)	OTV2X99A	XPO2_HUMAN	Affects Expression	[7]
Nucleosome assembly protein 1-like 1 (NAP1L1)	OTI7WBZV	NP1L1_HUMAN	Affects Expression	[7]
Large ribosomal subunit protein eL27 (RPL27)	OTWEOUTX	RL27_HUMAN	Affects Expression	[7]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Decreases Activity	[31]
Small ribosomal subunit protein uS15 (RPS13)	OTOMDIJ2	RS13_HUMAN	Affects Expression	[7]
Small ribosomal subunit protein eS28 (RPS28)	OT12IES1	RS28_HUMAN	Affects Expression	[7]
Large ribosomal subunit protein eL32 (RPL32)	OTKRQJT4	RL32_HUMAN	Affects Expression	[7]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Affects Expression	[7]
Large ribosomal subunit protein eL6 (RPL6)	OTRU71O4	RL6_HUMAN	Affects Expression	[7]
Single-stranded DNA-binding protein, mitochondrial (SSBP1)	OTH2PZWH	SSBP_HUMAN	Affects Expression	[7]
Protein kinase C delta type (PRKCD)	OTSEH90E	KPCD_HUMAN	Increases Localization	[16]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[26]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[18]
ATP-dependent RNA helicase A (DHX9)	OT5AAOQI	DHX9_HUMAN	Affects Expression	[7]
Fibrinogen-like protein 1 (FGL1)	OTT0QHQ1	FGL1_HUMAN	Affects Expression	[7]
Serine/threonine-protein kinase 3 (STK3)	OTLNSCQD	STK3_HUMAN	Affects Expression	[7]
DnaJ homolog subfamily C member 3 (DNAJC3)	OT7ROIJF	DNJC3_HUMAN	Decreases Expression	[15]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[16]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Localization	[29]
Protein Smaug homolog 2 (SAMD4B)	OTVRZJ5D	SMAG2_HUMAN	Affects Expression	[7]
Chondroitin sulfate proteoglycan 4 (CSPG4)	OTW2D6DE	CSPG4_HUMAN	Affects Expression	[7]
Ribosomal protein eS27-like (RPS27L)	OTZWHU0N	RS27L_HUMAN	Affects Expression	[7]
Endoplasmic reticulum metallopeptidase 1 (ERMP1)	OT9CIEO2	ERMP1_HUMAN	Affects Expression	[7]
E3 ubiquitin-protein ligase RBBP6 (RBBP6)	OTTVG4HU	RBBP6_HUMAN	Affects Expression	[7]
Out at first protein homolog (OAF)	OTOR9CR5	OAF_HUMAN	Affects Expression	[7]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[17]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[17]
Shieldin complex subunit 2 (SHLD2)	OTMLERXL	SHLD2_HUMAN	Affects Expression	[7]
G-protein coupled bile acid receptor 1 (GPBAR1)	OT4BKEJ9	GPBAR_HUMAN	Decreases Expression	[15]
E3 ubiquitin-protein ligase rififylin (RFFL)	OT85MGDH	RFFL_HUMAN	Affects Expression	[7]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[32]
AP-2 complex subunit mu (AP2M1)	OTQCOSFN	AP2M1_HUMAN	Affects Expression	[7]
Ribosomal protein eL39-like 2 (RPL39L)	OTAV1MJQ	RL39L_HUMAN	Affects Expression	[7]
Rho GTPase-activating protein 7 (DLC1)	OTP8LMCR	RHG07_HUMAN	Increases Expression	[31]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Expression	[15]
Protein sprouty homolog 4 (SPRY4)	OT2VK9N0	SPY4_HUMAN	Affects Expression	[7]
Endosialin (CD248)	OTEBWORQ	CD248_HUMAN	Affects Expression	[7]
Soluble lamin-associated protein of 75 kDa (FAM169A)	OT2FDMA1	F169A_HUMAN	Affects Expression	[7]
Sulfotransferase 2A1 (SULT2A1)	OT0ISKQ4	ST2A1_HUMAN	Increases Sulfation	[33]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Increases Uptake	[10]

Indication(s) of Quinine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[6]

Quinine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
E3 ubiquitin-protein ligase COP1 (RFWD2)	TT05DLS	COP1_HUMAN	Modulator	[34]

Quinine Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[35]
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[36]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[37]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[38]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[39]
Na(+)/Cl(-) betaine/GABA transporter (SLC6A12)	DTBPTJF	S6A12_HUMAN	Substrate	[40]

Quinine Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[41]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[42]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[43]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[44]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[44]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[45]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[46]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[47]

Quinine Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[48]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Activity	[48]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[48]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases Expression	[49]
Solute carrier family 22 member 2 (SLC22A2)	OTGFK1AL	S22A2_HUMAN	Decreases Activity	[50]
Solute carrier family 22 member 1 (SLC22A1)	OT7817I4	S22A1_HUMAN	Decreases Activity	[50]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Uptake	[51]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Activity	[52]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Activity	[52]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[49]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[53]
Sodium/hydrogen exchanger 7 (SLC9A7)	OTVDLTYA	SL9A7_HUMAN	Decreases Activity	[54]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2)	OTO70C5O	SO1A2_HUMAN	Increases Uptake	[55]

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