SLC10A1

Summary

SLC10A1 (solute carrier family 10 member 1, HGNC:10905) is a protein-coding gene on chromosome 14q24.1, encoding Hepatic sodium/bile acid cotransporter (Q14973). As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins.

The protein encoded by this gene belongs to the sodium/bile acid cotransporter family, which are integral membrane glycoproteins that participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids; the ileal sodium/bile acid cotransporter with an apical cell localization that absorbs bile acids from the intestinal lumen, bile duct and kidney, and the liver-specific sodium/bile acid cotransporter, represented by this protein, that is found in the basolateral membranes of hepatocytes. Bile acids are the catabolic product of cholesterol metabolism, hence this protein is important for cholesterol homeostasis.

Source: NCBI Gene 6554 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholanemia, familial, 2 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 175 total — 7 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003049

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10905
Approved symbol	SLC10A1
Name	solute carrier family 10 member 1
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	NTCP, NTCP1
Ensembl gene	ENSG00000100652
Ensembl biotype	protein_coding
OMIM	182396
Entrez	6554

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000216540, ENST00000871514, ENST00000871515, ENST00000871516, ENST00000871517, ENST00000871518, ENST00000871519

RefSeq mRNA: 1 — MANE Select: NM_003049 NM_003049

CCDS: CCDS9797

Canonical transcript exons

ENST00000216540 — 5 exons

Exon	Start	End
ENSE00000658821	69778333	69778529
ENSE00000658822	69779182	69779360
ENSE00000658823	69786097	69786307
ENSE00000807857	69775416	69776388
ENSE00000807858	69796800	69797241

Expression profiles

Bgee: expression breadth broad, 74 present calls, max score 95.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7301 / max 443.0807, expressed in 21 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143896	0.3868	11
143897	0.1778	9
143895	0.1500	19
143894	0.0155	4

Top tissues by expression

215 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.94	gold quality
liver	UBERON:0002107	94.33	gold quality
left ventricle myocardium	UBERON:0006566	79.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.07	gold quality
olfactory bulb	UBERON:0002264	78.13	gold quality
type B pancreatic cell	CL:0000169	77.92	gold quality
CA1 field of hippocampus	UBERON:0003881	76.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.37	silver quality
tongue squamous epithelium	UBERON:0006919	74.57	gold quality
ileal mucosa	UBERON:0000331	73.15	silver quality
diaphragm	UBERON:0001103	73.15	gold quality
hair follicle	UBERON:0002073	72.34	gold quality
vastus lateralis	UBERON:0001379	71.92	gold quality
quadriceps femoris	UBERON:0001377	70.95	gold quality
pancreatic ductal cell	CL:0002079	69.38	silver quality
orbitofrontal cortex	UBERON:0004167	66.93	gold quality
nasal cavity epithelium	UBERON:0005384	66.66	gold quality
tibialis anterior	UBERON:0001385	66.26	silver quality
myocardium	UBERON:0002349	66.12	gold quality
Brodmann (1909) area 46	UBERON:0006483	65.49	gold quality
endothelial cell	CL:0000115	64.03	gold quality
sural nerve	UBERON:0015488	61.88	silver quality
gluteal muscle	UBERON:0002000	61.68	gold quality
heart right ventricle	UBERON:0002080	61.67	gold quality
triceps brachii	UBERON:0001509	61.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.31	gold quality
upper arm skin	UBERON:0004263	61.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.07	gold quality
bone marrow cell	CL:0002092	59.88	silver quality
cranial nerve II	UBERON:0000941	59.82	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.13
E-CURD-119	no	8181.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG, FOXA2, HHEX, HNF1A, HNF4A, JUN, NR0B2, NR1H4, NR3C1, RARA, RXRA, SPI1, STAT5A, TCF3

miRNA regulators (miRDB)

31 targeting SLC10A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-562	97.66	65.63	698
HSA-MIR-890	97.47	68.67	982
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-1225-5P	96.76	66.85	417
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-8081	96.42	67.75	738
HSA-MIR-1229-5P	94.57	65.78	487

Literature-anchored findings (GeneRIF, showing 40)

• Translation/insertion scanning, alanine insertion, and glycosylation site mutagenesis studies of liver sodium/bile acid cotransporter support a topography with nine membrane-spanning or membrane-associated segments. (PMID:12044156)
• a domain critical for bile acid substrate recognition of SLC10A1 has an ethnicity-dependent polymorphism (PMID:14660639)
• Conserved NTCP/Ntcp 5’-regulatory region transcription regulation differs among species and is not directly regulated by small heterodimer partner. Bile acids may regulate NTCP/Ntcp indirectly by modulating nuclear factor regulation of gene expression. (PMID:14701722)
• The present studies were undertaken to establish a suitable in vitro experimental model to study human ASBT function and its regulation by cholesterol. (PMID:15604201)
• The major canalicular transporter genes are expressed at mid-gestational stage during human fetal development. (PMID:15922475)
• Results suggest that the Ser-226 in the third cytoplasmic loop of NTCP is phosphorylated and cAMP may increase NTCP translocation to the cell membrane by dephosphorylating NTCP at this site. (PMID:16027164)
• The GR/dexamethasone activation of the hNTCP promoter is counteracted by bile acids and small heterodimer partner, providing a negative feedback mechanism for bile acid uptake in human hepatocytes. (PMID:16123152)
• Cholesterol treatment led to increased levels of NTCP and OCT-1 mRNAs. (PMID:17635184)
• Report PKCepsilon-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line. (PMID:19815625)
• The mRNA expression levels of sodium taurocholate cotransporting polypeptide, bile salt export pump, and hepatic cholesterol 7alpha-hydroxylase were significantly higher in the primary biliary cirrhosis patients than in the controls. (PMID:20857261)
• Inhibition of taurocholate uptake by nitric oxide involves S-nitrosylation of NTCP. (PMID:21109590)
• essential role of Na+-taurocholate co-transporting polypeptide (NTCP) in the uptake of bile acids, by which the enterohepatic recirculation of bile acids is maintained (PMID:21341987)
• NTCP adopts a dimeric structure in which individual subunits are functional. Bile salt uptake is influenced by heterodimerization when this impairs NTCP plasma membrane trafficking. (PMID:22029531)
• Patients undergoing partial hepatectomy with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. (PMID:22098322)
• these results suggest that the plasma membrane localization rather than kinase activity of PKCdelta plays an important role in cAMP-induced NTCP translocation and Rab4 activity (PMID:22744337)
• NTCP is a functional receptor for human hepatitis B and D virus. (PMID:23150796)
• Data suggest that, in SLC10A1, amino acid residues along one face of transmembrane domain 5 do not play direct role in substrate transport but are critical for sodium/bile acid transport functions of SLC10A1, most likely through helical stability. (PMID:23815591)
• This study was conducted to determine which of the 8 cysteine residues of NTCP is responsible for nitric oxide-mediated S-nitrosylation and inhibition of taurocholate uptake. (PMID:23886862)
• Polymorphisms in CYP2C9, CYP2C19 and SLC10A1 had minimal lipid-lowering effects. (PMID:23930675)
• Knockdown analysis suggested that HBV infection of HepG2-hNTCP-C4 cells was mediated by NTCP. (PMID:24342612)
• Human NTCP is a specific receptor for hepatitis B and D viruses, allowing virus entry into hepatocytes. (PMID:24361467)
• Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on NTCP. (PMID:24390325)
• findings suggest that the rs2296651 polymorphism in NTCP may predispose the susceptibility to and chronicity of HBV infection (PMID:24735529)
• This study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. (PMID:25010264)
• hNTCP is an electrogenic Na(+)-dependent transporter (PMID:25168282)
• Computer screening of NTCP inhibitors and non-inhibitors showed no relationship between the drugs and drug induced liver injury. (PMID:25220493)
• NTCP is a functional receptor for hepatitis B virus and hepatitis D virus. (PMID:25409679)
• Data indicate that retinoic acid receptor (RAR) is crucial for regulating sodium taurocholate cotransporting polypeptide (NTCP) expression that determines permissiveness to hepatitis B virus (HBV) infection. (PMID:25550158)
• Interleukin 6 inhibits HBV entry through downregulation of NTCP. (PMID:25765005)
• The observation that the pharmacological inhibitors of the NTCP transporter could block HBV entry suggests that NTCP represents an attractive molecular target for therapeutic intervention in HBV infection. (PMID:25929767)
• NTCP polymorphism play a critical role in the individual variability of rosuvastatin pharmacokinetics in Chinese healthy males (PMID:25985569)
• Liver nuclear receptors, FXR and SHP, and bile acid transporters, NTCP and BSEP, are associated with the progression of NAFLD. (PMID:26019035)
• Hepatitis B virus efficiently infects non-adherent hepatoma cells via NTCP, which functions as a virus receptor. (PMID:26592202)
• The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of progression to Liver cirrhosis and Hepatocellular Carcinoma , and resistance to Chronic Hepatitis B infection. (PMID:26642861)
• We describe for the first time a mouse liver cell line that, solely upon expression of the hNTCP receptor, becomes susceptible to HBV. (PMID:26865711)
• We found a genetic variant (rs4646287) located in intron 1 of NTCP that may be associated with increased risk of HBV infection in Han Chinese (PMID:26968990)
• For Tibetans and Uygurs, no association of the three NTCP SNPs (rs7154439, rs4646287 and rs2296651) and their haplotypes with hepatitis B virus chronicity was observed. (PMID:27051045)
• Results show that NTCP inhibition suppressed the in vivo spread of HBV infection in the presence of uninfected hepatocytes. Livers in CHB patients contained varying degrees of HBsAg-negative hepatocytes, as evidenced by immunohistochemistry. (PMID:27278060)
• In conclusion, NTCP appeared inefficient to mediate infection by serum-derived hepatitis B virus. (PMID:27384660)
• the present study indicated that the common variants in the regulatory elements of NTCP may not influence the expression level of SLC10A1 at transcriptional regulation, and ultimately may not be associated with HBV susceptibility. (PMID:27491457)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc10a1	ENSDARG00000030588
mus_musculus	Slc10a1	ENSMUSG00000021135
rattus_norvegicus	Slc10a1	ENSRNOG00000005794

Paralogs (5): SLC10A2 (ENSG00000125255), SLC10A3 (ENSG00000126903), SLC10A4 (ENSG00000145248), SLC10A6 (ENSG00000145283), SLC10A5 (ENSG00000253598)

Protein

Protein identifiers

Hepatic sodium/bile acid cotransporter — Q14973 (reviewed: Q14973)

Alternative names: Cell growth-inhibiting gene 29 protein, Na(+)/bile acid cotransporter, Na(+)/taurocholate transport protein, Sodium/taurocholate cotransporting polypeptide, Solute carrier family 10 member 1

All UniProt accessions (1): Q14973

UniProt curated annotations — full annotation on UniProt →

Function. As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins. It is strictly dependent on the extracellular presence of sodium. It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate. Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation. (Microbial infection) Acts as an entry receptor for hepatitis B virus (HBV). The recognition for human SLC10A1/NTCP is highly specific.

Subunit / interactions. (Microbial infection) Interacts with the myristoylated pre-S1 domain of hepatitis B virus large envelope protein; myristoylation is essential for this interaction.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in liver. Expressed in placental trophoblasts.

Disease relevance. Hypercholanemia, familial, 2 (FHCA2) [MIM:619256] An autosomal recessive inborn error of metabolism characterized by persistently increased plasma levels of conjugated bile salts apparent from infancy, fat malabsorption and impaired absorption of fat-soluble vitamins, including D and K. Most patients are asymptomatic. Some neonates may have transient jaundice or transiently elevated liver enzymes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The transport of bile acids is sodium-dependent.

Similarity. Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.

RefSeq proteins (1): NP_003040* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002657	BilAc:Na_symport/Acr3	Family
IPR004710	Bilac:Na_transpt	Family
IPR038770	Na+/solute_symporter_sf	Homologous_superfamily

Pfam: PF01758

Catalyzed reactions (Rhea), 12 shown:

• tauroallocholate(out) + 2 Na(+)(out) = tauroallocholate(in) + 2 Na(+)(in) (RHEA:51840)
• estrone 3-sulfate(out) + 2 Na(+)(out) = estrone 3-sulfate(in) + 2 Na(+)(in) (RHEA:71083)
• taurocholate(out) + 2 Na(+)(out) = taurocholate(in) + 2 Na(+)(in) (RHEA:71875)
• cholate(out) + 2 Na(+)(out) = cholate(in) + 2 Na(+)(in) (RHEA:71911)
• tauronorcholate(out) + 2 Na(+)(out) = tauronorcholate(in) + 2 Na(+)(in) (RHEA:71915)
• taurochenodeoxycholate(out) + 2 Na(+)(out) = taurochenodeoxycholate(in) + 2 Na(+)(in) (RHEA:71923)
• tauroursodeoxycholate(out) + 2 Na(+)(out) = tauroursodeoxycholate(in) + 2 Na(+)(in) (RHEA:71927)
• glycocholate(out) + 2 Na(+)(out) = glycocholate(in) + 2 Na(+)(in) (RHEA:71935)
• taurodeoxycholate(out) + 2 Na(+)(out) = taurodeoxycholate(in) + 2 Na(+)(in) (RHEA:72087)
• taurohyodeoxycholate(out) + 2 Na(+)(out) = taurohyodeoxycholate(in) + 2 Na(+)(in) (RHEA:72167)
• taurohyocholate(out) + 2 Na(+)(out) = taurohyocholate(in) + 2 Na(+)(in) (RHEA:72171)
• tauro-beta-muricholate(out) + 2 Na(+)(out) = tauro-beta-muricholate(in) + 2 Na(+)(in) (RHEA:72179)

UniProt features (78 total): sequence variant 24, helix 18, topological domain 10, mutagenesis site 10, transmembrane region 9, glycosylation site 2, strand 2, turn 2, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7ZYI	ELECTRON MICROSCOPY	2.88
8HRX	ELECTRON MICROSCOPY	2.89
8HRY	ELECTRON MICROSCOPY	3.11
9QZQ	ELECTRON MICROSCOPY	3.11
7FCI	ELECTRON MICROSCOPY	3.3
7PQQ	ELECTRON MICROSCOPY	3.3
7VAG	ELECTRON MICROSCOPY	3.32
7WSI	ELECTRON MICROSCOPY	3.32
7VAD	ELECTRON MICROSCOPY	3.41
8RQF	ELECTRON MICROSCOPY	3.41
7PQG	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14973-F1	83.79	0.59

Antibody-complex structures (SAbDab): 11 — 7FCI, 7PQG, 7PQQ, 7VAD, 7VAG, 7WSI, 7ZYI, 8HRX, 8HRY, 8RQF, 9QZQ

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 5, 11

Mutagenesis-validated functional residues (10):

Position	Phenotype
20	disrupts interaction with hbv myristoylated pre-s1 peptide.
27	disrupts interaction with hbv myristoylated pre-s1 peptide. abolishes pre-s1-mediated attactment to hbv and the transpor
31	abolishes pre-s1-mediated attactment to hbv and the transport of bile acid; when associated with w-27. abolishes pre-s1-
35	abolishes pre-s1-mediated attactment to hbv and the transport of bile acid; when associated with w-31. abolishes pre-s1-
202	disrupts interaction with hbv myristoylated pre-s1 peptide.
261	abolishes interaction with hbv myristoylated pre-s1 peptide.
263	disrupts interaction with hbv myristoylated pre-s1 peptide.
264	disrupts interaction with hbv myristoylated pre-s1 peptide, reduces bile acid transport and reduces hbv infection.
268	disrupts interaction with hbv myristoylated pre-s1 peptide, reduces bile acid transport and reduces hbv infection.
272	disrupts interaction with hbv myristoylated pre-s1 peptide, reduces bile acid transport and reduces hbv infection.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-159418	Recycling of bile acids and salts

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): bile acid and bile salt transport (GO:0015721), response to nutrient levels (GO:0031667), response to estrogen (GO:0043627), response to ethanol (GO:0045471), cellular response to xenobiotic stimulus (GO:0071466), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), lipid transport (GO:0006869), symbiont entry into host cell (GO:0046718), transmembrane transport (GO:0055085)

GO Molecular Function (5): virus receptor activity (GO:0001618), bile acid:sodium symporter activity (GO:0008508), bile acid transmembrane transporter activity (GO:0015125), protein binding (GO:0005515), symporter activity (GO:0015293)

GO Cellular Component (3): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Bile acid and bile salt metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
response to stimulus	1
response to hormone	1
response to alcohol	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
metal ion transport	1
lipid localization	1
viral life cycle	1
symbiont entry into host	1
cellular process	1
symbiont entry into host cell	1
exogenous protein binding	1
organic acid:sodium symporter activity	1
bile acid transmembrane transporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
bile acid and bile salt transport	1
carboxylic acid transmembrane transporter activity	1
lipid transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC10A1	SLCO1A2	P46721	928
SLC10A1	SLC10A7	Q0GE19	916
SLC10A1	ABCB11	O95342	890
SLC10A1	CYP7A1	P22680	888
SLC10A1	NR1H4	Q96RI1	861
SLC10A1	FABP6	P51161	858
SLC10A1	EGFR	P00533	853
SLC10A1	SLC26A5	P58743	845
SLC10A1	NR0B2	Q15466	837
SLC10A1	SLCO1B1	Q9Y6L6	831
SLC10A1	SLCO1B3	Q9NPD5	812
SLC10A1	SLC51A	Q86UW1	797
SLC10A1	CYP8B1	Q9UNU6	796
SLC10A1	ERVW-1	Q9UQF0	795
SLC10A1	ERVFRD-1	P60508	792
SLC10A1	ERV3-1	Q14264	792

IntAct

278 interactions, top by confidence:

A	B	Type	Score
SLC10A1	ARL6IP6	psi-mi:“MI:0915”(physical association)	0.670
PEX16	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
OTOP3	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
C8A	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
CFHR5	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
MS4A1	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
TMEM147	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
ORMDL3	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
SFT2D1	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
MALL	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
IFITM3	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	DERL1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	SELENOK	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	LRP10	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	ORMDL3	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	YIPF4	psi-mi:“MI:0915”(physical association)	0.560
TFRC	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (151): SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC10A1 (Two-hybrid), SLC38A7 (Two-hybrid), FA2H (Two-hybrid), TMEM147 (Two-hybrid), GOSR2 (Two-hybrid), SLC38A1 (Two-hybrid), TSPO2 (Two-hybrid), SLC12A7 (Two-hybrid)

ESM2 similar proteins: A0AV02, A2AWR3, A2VCW5, A4QN56, A6QP84, B2RXV4, D4A7H1, F7B113, G8XYX6, O08705, O70324, P09131, P19634, P21129, P23791, P26431, P26434, P26435, P36021, P48761, P48762, P97751, Q0V8N6, Q14973, Q28036, Q3KNW5, Q3UEZ8, Q4JLT5, Q5PT54, Q5PT56, Q5R9A7, Q61165, Q70EX6, Q71RS6, Q7Z3F1, Q8BFW9, Q8BLV3, Q8BUE1, Q8BZ00, Q8C261

Diamond homologs: A6QP84, O08705, P09131, P26435, P70172, Q12908, Q14973, Q28727, Q3KNW5, Q3UEZ8, Q4JLT5, Q5PT55, Q5PT56, Q60414, Q62633, Q70EX6, Q7XVB3, Q96EP9, Q9CXB2, P21129, Q0V8N6, Q93YR2, B8BDK4, F4JPW1, Q5PT54, Q650U0, Q8VYY4, Q1EBV7, Q5VRB2, O34524, Q6K739, Q8RXE8, Q8ZKL0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

175 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	7
Uncertain significance	120
Likely benign	26
Benign	8

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1705419	NM_003049.4(SLC10A1):c.713_717del (p.Tyr238fs)	Likely pathogenic
2634668	NM_003049.4(SLC10A1):c.615_618del (p.Ser206fs)	Likely pathogenic
2635476	NM_003049.4(SLC10A1):c.397_403del (p.Met133fs)	Likely pathogenic
2636312	NM_003049.4(SLC10A1):c.4G>T (p.Glu2Ter)	Likely pathogenic
3357645	NM_003049.4(SLC10A1):c.617_618del (p.Ser206fs)	Likely pathogenic
3358124	NM_003049.4(SLC10A1):c.682dup (p.Leu228fs)	Likely pathogenic
4849384	NM_003049.4(SLC10A1):c.356+2T>G	Likely pathogenic

SpliceAI

620 predictions. Top by Δscore:

Variant	Effect	Δscore
14:69786091:TCTTA:T	donor_loss	1.0000
14:69786092:CTTAC:C	donor_loss	1.0000
14:69786093:TTACC:T	donor_loss	1.0000
14:69786094:TA:T	donor_loss	1.0000
14:69786095:ACCT:A	donor_loss	1.0000
14:69786096:C:A	donor_loss	1.0000
14:69796797:TA:T	donor_loss	1.0000
14:69796798:AC:A	donor_loss	1.0000
14:69796799:C:CG	donor_loss	1.0000
14:69778407:A:C	acceptor_gain	0.9900
14:69779180:A:AC	donor_gain	0.9900
14:69779181:C:CC	donor_gain	0.9900
14:69779356:CCTCC:C	acceptor_gain	0.9900
14:69779357:CTCC:C	acceptor_gain	0.9900
14:69779357:CTCCC:C	acceptor_gain	0.9900
14:69779358:TCCCT:T	acceptor_gain	0.9900
14:69779359:CC:C	acceptor_gain	0.9900
14:69779360:CC:C	acceptor_gain	0.9900
14:69779361:CTG:C	acceptor_loss	0.9900
14:69779362:T:A	acceptor_loss	0.9900
14:69786303:CAATG:C	acceptor_gain	0.9900
14:69786305:ATG:A	acceptor_gain	0.9900
14:69786306:TG:T	acceptor_gain	0.9900
14:69786308:C:CC	acceptor_gain	0.9900
14:69786320:A:C	acceptor_gain	0.9900
14:69778406:CATG:C	acceptor_gain	0.9800
14:69778409:G:C	acceptor_gain	0.9800
14:69779176:ACCT:A	donor_loss	0.9800
14:69779177:CCTA:C	donor_loss	0.9800
14:69779179:TA:T	donor_loss	0.9800

AlphaMissense

2285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:69778490:A:C	N262K	0.995
14:69778490:A:T	N262K	0.995
14:69778454:A:C	F274L	0.990
14:69778454:A:T	F274L	0.990
14:69778456:A:G	F274L	0.990
14:69796864:A:G	C98R	0.990
14:69778467:A:G	L270P	0.989
14:69778478:A:C	C266W	0.986
14:69778480:A:G	C266R	0.986
14:69778455:A:C	F274C	0.985
14:69796929:G:T	A76D	0.985
14:69778467:A:T	L270H	0.984
14:69796866:C:T	G97D	0.984
14:69778455:A:G	F274S	0.983
14:69796862:G:C	C98W	0.983
14:69778511:G:C	S255R	0.980
14:69778511:G:T	S255R	0.980
14:69778513:T:G	S255R	0.980
14:69796867:C:G	G97R	0.980
14:69786275:G:T	A130D	0.979
14:69796870:A:G	C96R	0.978
14:69778470:A:T	I269N	0.977
14:69796872:A:T	V95D	0.977
14:69786251:A:G	L138P	0.976
14:69786263:A:C	M134R	0.976
14:69796863:C:T	C98Y	0.975
14:69779230:C:T	G233D	0.973
14:69778479:C:T	C266Y	0.972
14:69778491:T:A	N262I	0.972
14:69796930:C:G	A76P	0.972

dbSNP variants (sampled 300 via entrez): RS1000117667 (14:69775680 C>A,T), RS1000167476 (14:69791168 A>G), RS1000205022 (14:69791073 G>A), RS1000301010 (14:69790939 A>G), RS1000324857 (14:69784688 A>G), RS1000338937 (14:69790866 T>C), RS1000554630 (14:69776443 T>C), RS1000592088 (14:69784940 T>A), RS1000610999 (14:69780588 T>G), RS1000661540 (14:69779819 C>T), RS1000818538 (14:69779602 C>T), RS1000852573 (14:69797111 T>C), RS1001139692 (14:69795446 C>G), RS1001211080 (14:69789511 T>A,C), RS1001225569 (14:69776662 A>G)

Disease associations

OMIM: gene MIM:182396 | disease phenotypes: MIM:619256

GenCC curated gene-disease

Disease	Classification	Inheritance
hypercholanemia, familial, 2	Strong	Autosomal recessive

Mondo (1): hypercholanemia, familial, 2 (MONDO:0031003)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000938	Osteopenia
HP:0003623	Neonatal onset
HP:0006579	Prolonged neonatal jaundice
HP:0008282	Unconjugated hyperbilirubinemia
HP:0012202	Increased serum bile acid concentration
HP:0100512	Decreased circulating vitamin D concentration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003518_91	Daytime sleep phenotypes	2.000000e-06
GCST006436_13	Triglyceride levels	1.000000e-09
GCST009391_509	Metabolite levels	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004530	triglyceride measurement
EFO:0010527	pyridoxate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5287 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,044,061 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1138	EZETIMIBE	4	29,509
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL1513	IRBESARTAN	4	31,667
CHEMBL1551	URSODIOL	4	22,553
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL163	RITONAVIR	4	53,773
CHEMBL2220442	FLUVASTATIN	4	53,699
CHEMBL27	PROPRANOLOL	4	85,886
CHEMBL35	FUROSEMIDE	4	224,045
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL140	CURCUMIN	3	93,882
CHEMBL1829174	FASIGLIFAM	3	815
CHEMBL41632	TIRATRICOL	3	46,632
CHEMBL452861	LEVOPROPRANOLOL	2	77,655

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs56903885	SLC10A1		0.00	0
rs2296651	SLC10A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC10 family of sodium-bile acid co-transporters

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
(-)-propranolol	Inhibition	8.21	pIC50
ursodeoxycholic acid	Inhibition	5.44	pIC50
(+)-propranolol	Inhibition	5.26	pIC50
cyclosporin A	Inhibition	5.12	pKi
irbesartan	Inhibition	4.92	pKi

Binding affinities (BindingDB)

135 measured of 135 human assays (135 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(3-chloro-4-fluorophenyl)-1-[2-[(1-ethynyl-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	1.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-7-[2-[[3,3-difluoro-1-(triazolidin-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-N-(3,4,5-trifluorophenyl)-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	1.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-chloro-4-fluorophenyl)-7-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	2.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3,4-difluorophenyl)-7-[2-[[3,3-difluoro-1-(triazolidin-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	2.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-[3-(difluoromethyl)-4-fluorophenyl]-1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	2.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	3.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3,4-difluorophenyl)-1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	3.2 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-N-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	3.2 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-7-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-N-(4-fluorophenyl)-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	3.7 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[[1-(1,3,4-thiadiazol-2-yl)cyclopropyl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-cyano-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	5.6 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[[3-(trifluoromethyl)oxetan-3-yl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	5.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[(1-ethynylcyclopropyl)amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	5.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[(1-ethynylcyclopropyl)amino]-2-oxoacetyl]-2-methyl-N-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	6.4 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(6R)-1-[2-[[3,3-difluoro-1-(triazolidin-4-yl)cyclobutyl]amino]-2-oxoacetyl]-6-fluoro-N-(4-fluorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	6.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[(1-phenylcyclopropyl)amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	6.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
2-methyl-1-[2-oxo-2-[(1-phenylcyclopropyl)amino]acetyl]-N-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	6.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-cyano-4-fluorophenyl)-7-[2-[[3,3-difluoro-1-(triazolidin-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	7.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(6-oxa-1-azaspiro[3.3]heptane-1-carbonyl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	7.7 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-chloro-4-fluorophenyl)-8-methyl-7-[2-oxo-2-[[1-(2H-triazol-4-yl)cyclopropyl]amino]acetyl]-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	7.7 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-chloro-4-fluorophenyl)-8-methyl-7-[2-oxo-2-[[1-(1,3,4-thiadiazol-2-yl)cyclopropyl]amino]acetyl]-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	7.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[(1,1,1-trifluoro-3-hydroxy-2-methylpropan-2-yl)amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	8.3 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-N-(4-fluorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	8.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R)-N-[2-(difluoromethyl)-3-fluoro-4-pyridinyl]-7-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	8.7 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[[3-(2H-triazol-4-yl)oxetan-3-yl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	8.7 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-chloro-4-fluorophenyl)-7-[2-[[3,3-difluoro-1-(methylcarbamoyl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	8.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(3-fluoroazetidine-1-carbonyl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	8.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(6R)-N-(3-chloro-4-fluorophenyl)-6-fluoro-2-methyl-1-[2-oxo-2-[[1-(triazolidin-4-yl)cyclopropyl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	9.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-8-methyl-7-[2-oxo-2-[[1-(1,3,4-thiadiazol-2-yl)cyclopropyl]amino]acetyl]-N-(3,4,5-trifluorophenyl)-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	9.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[(1-cyano-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	10.4 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[(1-cyano-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-N-(3,4-difluorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	10.6 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[[1-(2H-triazol-4-yl)cyclopropyl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	11.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[1-(dimethylcarbamoyl)-3,3-difluorocyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	11.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[(1-carbamoyl-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-2-methyl-N-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	12.2 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3,4-difluorophenyl)-8-methyl-7-[2-oxo-2-[[1-(1,3,4-thiadiazol-2-yl)cyclopropyl]amino]acetyl]-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	12.3 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[(1-carbamoyl-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-N-(3-chloro-4-fluorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	12.3 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
[4-[3-[[2-[(2R,4R)-9-[(3,4-difluorophenyl)carbamoyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-dien-7-yl]-2-oxoacetyl]amino]oxetan-3-yl]triazol-1-yl]methyl 2,2-dimethylpropanoate	EC50	12.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-7-[2-[[3,3-difluoro-1-(methylcarbamoyl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-N-(3,4,5-trifluorophenyl)-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	13 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(hydroxymethyl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	13.1 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
1-[2-[(1-carbamoyl-3,3-difluorocyclobutyl)amino]-2-oxoacetyl]-N-(3,4-difluorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	14.4 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
2-methyl-1-[2-oxo-2-[[1-(2H-triazol-4-yl)cyclopropyl]amino]acetyl]-N-(3,4,5-trifluorophenyl)-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	14.6 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-1-[2-[[3,3-difluoro-1-(methylcarbamoyl)cyclobutyl]amino]-2-oxoacetyl]-2-methyl-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	14.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3-chloro-4-fluorophenyl)-8-methyl-7-[2-[(3-methyl-1,1-dioxothietan-3-yl)amino]-2-oxoacetyl]-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	15.4 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-8-methyl-7-[2-[(3-methyl-1,1-dioxothietan-3-yl)amino]-2-oxoacetyl]-N-(3,4,5-trifluorophenyl)-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	15.8 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3-chloro-4-fluorophenyl)-2-methyl-1-[2-oxo-2-[[(2R)-1,1,1-trifluoropropan-2-yl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	15.9 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-[2-(difluoromethyl)-4-pyridinyl]-7-[2-[[3,3-difluoro-1-(2H-triazol-4-yl)cyclobutyl]amino]-2-oxoacetyl]-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	16.4 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-7-[2-[[3,3-difluoro-1-(methylcarbamoyl)cyclobutyl]amino]-2-oxoacetyl]-N-(3,4-difluorophenyl)-8-methyl-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	16.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-(3,4-difluorophenyl)-2-methyl-1-[2-oxo-2-[(1,1,1-trifluoro-3-hydroxy-2-methylpropan-2-yl)amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	16.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
(2R,4R)-N-(3,4-difluorophenyl)-8-methyl-7-[2-oxo-2-[[1-(triazolidin-4-yl)cyclopropyl]amino]acetyl]-1-azatricyclo[4.3.0.02,4]nona-6,8-diene-9-carboxamide	EC50	17.5 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof
N-[3-(difluoromethyl)-4-fluorophenyl]-2-methyl-1-[2-oxo-2-[[1-(triazolidin-4-yl)cyclopropyl]amino]acetyl]-6,7-dihydro-5H-pyrrolizine-3-carboxamide	EC50	19 nM	US-10328053: Substituted pyrrolizine compounds and uses thereof

ChEMBL bioactivities

201 potent at pChembl≥5 of 246 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL4875567
8.74	EC50	1.8	nM	CHEMBL6000938
8.72	EC50	1.9	nM	CHEMBL5995946
8.68	EC50	2.1	nM	CHEMBL6057770
8.68	EC50	2.1	nM	CHEMBL5931719
8.54	EC50	2.9	nM	CHEMBL5946125
8.51	EC50	3.1	nM	CHEMBL5795613
8.49	EC50	3.2	nM	CHEMBL5741380
8.49	EC50	3.2	nM	CHEMBL5814839
8.43	EC50	3.7	nM	CHEMBL5768748
8.30	EC50	5	nM	CHEMBL5879545
8.25	EC50	5.6	nM	CHEMBL5966964
8.24	EC50	5.8	nM	CHEMBL6062020
8.24	EC50	5.8	nM	CHEMBL5803990
8.19	EC50	6.5	nM	CHEMBL5787259
8.19	EC50	6.5	nM	CHEMBL5952889
8.19	EC50	6.5	nM	CHEMBL5756220
8.19	EC50	6.4	nM	CHEMBL5921954
8.12	EC50	7.5	nM	CHEMBL5913674
8.11	EC50	7.7	nM	CHEMBL5927182
8.11	EC50	7.7	nM	CHEMBL5934850
8.11	EC50	7.8	nM	CHEMBL5942628
8.08	EC50	8.3	nM	CHEMBL5934699
8.07	EC50	8.5	nM	CHEMBL5763508
8.06	EC50	8.8	nM	CHEMBL5869018
8.06	EC50	8.8	nM	CHEMBL5933166
8.06	EC50	8.7	nM	CHEMBL5937180
8.06	EC50	8.7	nM	CHEMBL5743886
8.04	EC50	9.1	nM	CHEMBL5897637
8.00	EC50	9.9	nM	CHEMBL5778868
7.98	EC50	10.4	nM	CHEMBL5825924
7.97	EC50	10.6	nM	CHEMBL5849735
7.96	EC50	11.1	nM	CHEMBL6059881
7.92	EC50	11.9	nM	CHEMBL5770819
7.91	EC50	12.3	nM	CHEMBL5829613
7.91	EC50	12.3	nM	CHEMBL5891468
7.91	EC50	12.2	nM	CHEMBL5782284
7.90	EC50	12.5	nM	CHEMBL5801597
7.89	EC50	13	nM	CHEMBL5745665
7.88	EC50	13.1	nM	CHEMBL5823213
7.85	IC50	14	nM	CHEMBL4849233
7.85	IC50	14	nM	CHEMBL4864019
7.85	IC50	14	nM	CHEMBL4869726
7.85	IC50	14	nM	CHEMBL4875540
7.85	IC50	14	nM	CHEMBL4861143
7.84	EC50	14.6	nM	CHEMBL6041631
7.84	EC50	14.4	nM	CHEMBL5908416
7.83	EC50	14.9	nM	CHEMBL5844309
7.81	EC50	15.4	nM	CHEMBL5904244
7.80	EC50	15.9	nM	CHEMBL6065083

PubChem BioAssay actives

51 with measured affinity, of 201 total; 41 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776412: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS	ic50	0.0003	uM
2-[[(4R)-4-[(3R,5R,7S,8R,9S,10S,13R,14S,17R)-3-[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]oxy-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776394: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells after 2 hrs	ic50	0.0140	uM
(1S,3S,4R,5S,8R,9S,12R,13R,24R,25R,28S,29R,32S,33R,34S,36S,37S,40R,48R,51S)-3,34-dihydroxy-8,13,24,29,37,51-hexamethyl-17,20,41,47-tetrazanonacyclo[46.3.1.136,40.04,9.05,51.08,12.025,29.028,33.032,37]tripentacontane-16,21,42,46-tetrone	1776394: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells after 2 hrs	ic50	0.0140	uM
2-[[(4R)-4-[(3R,5R,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-3-[5-[[(3R,5R,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-17-[(2R)-5-oxo-5-(2-sulfoethylamino)pentan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-5-oxopentanoyl]oxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776394: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells after 2 hrs	ic50	0.0140	uM
2-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-3-[4-[[(3R,5R,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-17-[(2R)-5-oxo-5-(2-sulfoethylamino)pentan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxymethyl]triazol-1-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776394: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells after 2 hrs	ic50	0.0140	uM
2-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-3-[[5-[[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-17-[(2R)-5-oxo-5-(2-sulfoethylamino)pentan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]amino]-5-oxopentanoyl]amino]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776394: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells after 2 hrs	ic50	0.0140	uM
(1R,8R,11S,12R,14S,15R,16S,19R,20S,23R,24R,35R,36R,39S,40R,43S,44R,45S,47S,48S)-14,45-dihydroxy-11,19,24,35,40,48-hexamethyl-27,32-dioxo-7-oxa-2,3,4,28,31-pentazadecacyclo[45.3.1.12,5.18,12.011,16.015,20.019,23.036,40.039,44.043,48]tripentaconta-3,5(53)-diene-29-carboxylic acid	1776412: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS	ic50	0.0179	uM
2-[[(1R,8R,11S,12R,14S,15R,16S,19R,20S,23R,24R,35R,36R,39S,40R,43S,44R,45S,47S,48S)-14,45-dihydroxy-11,19,24,35,40,48-hexamethyl-27,32-dioxo-7-oxa-2,3,4,28,31-pentazadecacyclo[45.3.1.12,5.18,12.011,16.015,20.019,23.036,40.039,44.043,48]tripentaconta-3,5(53)-diene-29-carbonyl]amino]ethanesulfonic acid	1776412: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS	ic50	0.0235	uM
2-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3-[4-[(3R)-3-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]butyl]triazol-1-yl]-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	1776412: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS	ic50	0.0245	uM
(1R,8R,11S,12R,14S,15R,16S,19R,20S,23R,24R,35R,36R,39S,40R,43S,44R,45S,47S,48S)-14,45-dihydroxy-11,19,24,35,40,48-hexamethyl-7-oxa-2,3,4,28,31-pentazadecacyclo[45.3.1.12,5.18,12.011,16.015,20.019,23.036,40.039,44.043,48]tripentaconta-3,5(53)-diene-27,32-dione	1776412: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS	ic50	0.0375	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-1,4,7,10,12,15,19,25,28-nonamethyl-33-[(2R,3R,5S)-3-methyl-5-(3-phenylmethoxyphenyl)sulfanyloxolan-2-yl]-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1707614: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells incubated for 2 hrs followed by substrate addition and measured for 10 mins by microbeta liquid scintillation counter analysis	ic50	0.0660	uM
2-[[(4R)-4-[(2S,12R,18R)-12-hydroxy-6-(2-hydroxyethyl)-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.2000	uM
2-[[(4R)-4-[(2S,18R)-6-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)oxyethyl]-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.2200	uM
2-[[(4R)-4-[(2S,18R)-6-[(3-hydroxyphenyl)methyl]-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.3000	uM
2-[[(4R)-4-[(2S,12R,18R)-12-hydroxy-6-[(3-hydroxyphenyl)methyl]-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.3000	uM
2-[[(4R)-4-[(2S,12R,18R)-12-hydroxy-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4(8),5-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.3000	uM
2-[[(4R)-4-[(2S,18R)-6-(2-hydroxyethyl)-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	0.7000	uM
cyclosporine	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	1.0000	uM
2-[[(4R)-4-[(2S,18R)-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4(8),5-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	1.6000	uM
2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid	1600826: Inhibition of NTCP in human hepatocytes	ic50	2.0000	uM
2-[[(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-7-(4-fluorobenzoyl)oxy-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid	1927078: Binding affinity to NTCP (unknown origin) assessed as inhibition constant	ki	2.5500	uM
2-[[(4R)-4-[(2S,12R,18R)-12-hydroxy-6-[[3-[(2S)-2-(6-methoxynaphthalen-2-yl)propanoyl]oxyphenyl]methyl]-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	3.4000	uM
ursodiol	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	3.6000	uM
(1S,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-propan-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol	1896150: Inhibition of HBV subgenotype D3 [3H]-myr-preS1 (2 to 48 residues) peptide binding to human NTCP in HEK293 cells preincubated for 5 mins followed by substrate addition and measured after 10 mins using by microplate scintillation counter analysis	ic50	4.0000	uM
2-[[(4R)-4-[(3R,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-7-oxo-1,2,3,4,5,6,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid	1927078: Binding affinity to NTCP (unknown origin) assessed as inhibition constant	ki	4.2100	uM
Rosiglitazone	1600822: Inhibition of HA-tagged human NTCP expressed in human U2OS cells assessed as reduction in [14C]taurocholate uptake preincubated for 10 mins followed by [14C] taurocholate addition and further incubation for 10 mins by scintillation counting method	ic50	5.1000	uM
2-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	5.3000	uM
2-[[(4R)-4-[(3R,5R,7R,8R,9S,10S,13R,14S,17R)-7-hydroxy-10,13-dimethyl-3-(pyridine-3-carbonyloxy)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid	1927078: Binding affinity to NTCP (unknown origin) assessed as inhibition constant	ki	5.3800	uM
Propranolol	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	5.5000	uM
[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate	1896150: Inhibition of HBV subgenotype D3 [3H]-myr-preS1 (2 to 48 residues) peptide binding to human NTCP in HEK293 cells preincubated for 5 mins followed by substrate addition and measured after 10 mins using by microplate scintillation counter analysis	ic50	6.0000	uM
(2S)-1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	6.1000	uM
(1S,2R,3S)-1-[4-[(1S,2R,3S)-1-hydroxy-3-phenyl-2-pyridin-2-yl-3-(pyridin-2-ylamino)propyl]phenyl]-3-phenyl-2-pyridin-2-yl-3-(pyridin-2-ylamino)propan-1-ol	1896150: Inhibition of HBV subgenotype D3 [3H]-myr-preS1 (2 to 48 residues) peptide binding to human NTCP in HEK293 cells preincubated for 5 mins followed by substrate addition and measured after 10 mins using by microplate scintillation counter analysis	ic50	6.5000	uM
Zafirlukast	1600822: Inhibition of HA-tagged human NTCP expressed in human U2OS cells assessed as reduction in [14C]taurocholate uptake preincubated for 10 mins followed by [14C] taurocholate addition and further incubation for 10 mins by scintillation counting method	ic50	6.5000	uM
2-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]acetic acid	1600822: Inhibition of HA-tagged human NTCP expressed in human U2OS cells assessed as reduction in [14C]taurocholate uptake preincubated for 10 mins followed by [14C] taurocholate addition and further incubation for 10 mins by scintillation counting method	ic50	6.9000	uM
4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonic acid	1896149: Inhibition of human NTCP mediated TCA uptake in U2OS expresseing HA-tagged NTCP cells preincubated for 10 mins followed by substrate addition and measured after 2 mins using [3H]-taurocholate as substrate by liquid scintillation counter analysis	ic50	7.1000	uM
disodium;2-hydroxy-5-[4,5,6,7-tetrabromo-1-(4-hydroxy-3-sulfonatophenyl)-3-oxo-2-benzofuran-1-yl]benzenesulfonate	681378: TP_TRANSPORTER: inhibition of Taurocholate uptake in NTCP-expressing HeLa cells	ic50	7.3000	uM
[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bS)-9-acetyloxy-1-(3-hydroxyprop-1-en-2-yl)-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-3a-yl]methyl acetate	1896150: Inhibition of HBV subgenotype D3 [3H]-myr-preS1 (2 to 48 residues) peptide binding to human NTCP in HEK293 cells preincubated for 5 mins followed by substrate addition and measured after 10 mins using by microplate scintillation counter analysis	ic50	8.0000	uM
2-[[(4R)-4-[(2S,12R,18R,19S)-12,19-dihydroxy-6-[(3-hydroxyphenyl)methyl]-2,18-dimethyl-6,7-diazapentacyclo[11.7.0.02,10.04,8.014,18]icosa-4,7-dien-17-yl]pentanoyl]amino]acetic acid	242784: In vitro inhibition of taurocholate binding to liver bile acid transporter expressed in CHO cells	ic50	8.6000	uM
(2S)-2-[[2-[(Z)-[(8R,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]amino]oxyacetyl]amino]-3-hydroxybutanoic acid	1896137: Inhibition of HBV subgenotype D3 derived [3H]preS1-peptide binding to human NTCP in HEK293 cells overexpressing NTCP preincubated for 5 mins followed by [3H]preS1 addition and measured after 10 mins by liquid scintillation counter analysis	ic50	9.0000	uM
2-[[(4R)-4-[(3R,5S,7R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-7-(pyridine-3-carbonyloxy)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]acetic acid	1927078: Binding affinity to NTCP (unknown origin) assessed as inhibition constant	ki	9.2900	uM
2-hydroxy-5-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid	1600822: Inhibition of HA-tagged human NTCP expressed in human U2OS cells assessed as reduction in [14C]taurocholate uptake preincubated for 10 mins followed by [14C] taurocholate addition and further incubation for 10 mins by scintillation counting method	ic50	9.6000	uM

CTD chemical–gene interactions

140 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Taurocholic Acid	increases reaction, affects reaction, affects cotreatment, increases import, decreases reaction (+2 more)	13
Cyclosporine	affects cotreatment, decreases expression, decreases reaction, increases uptake, decreases activity (+2 more)	10
Tetrachlorodibenzodioxin	affects expression, decreases expression	7
Bile Acids and Salts	decreases reaction, increases uptake, affects transport, affects uptake, increases transport	6
Chenodeoxycholic Acid	decreases reaction, affects cotreatment, decreases expression, increases uptake	5
Glycochenodeoxycholic Acid	decreases expression, increases uptake, decreases reaction, affects cotreatment	4
Sodium	affects cotreatment, decreases reaction, increases uptake, increases import	4
perfluorooctane sulfonic acid	affects expression, increases expression, increases transport	3
Troglitazone	decreases reaction, increases uptake, decreases expression	3
Bosentan	decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	3
Deoxycholic Acid	affects cotreatment, decreases expression, increases uptake, decreases reaction	3
Glycocholic Acid	decreases reaction, affects cotreatment, decreases expression, increases uptake	3
Glycodeoxycholic Acid	decreases reaction, increases uptake, affects cotreatment, decreases expression	3
Phenobarbital	decreases expression, increases expression	3
Triclosan	affects cotreatment, decreases expression	3
Aflatoxin B1	decreases expression, affects expression	3
estrone sulfate	increases transport, increases reaction, increases uptake, decreases reaction	2
perfluorooctanoic acid	affects expression, increases expression	2
TAK-875	decreases reaction, increases transport, decreases activity	2
Acetaminophen	affects cotreatment, decreases expression	2
Dexamethasone	increases expression	2
Rifampin	decreases expression, affects cotreatment, increases expression	2
Sulfobromophthalein	decreases reaction, increases uptake	2
Tobacco Smoke Pollution	increases import, decreases expression, increases expression, decreases reaction	2
Valproic Acid	decreases activity, decreases expression	2
Cholic Acid	decreases expression, increases uptake, decreases reaction	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases reaction, increases uptake	1
perfluorodecanesulfonic acid	increases expression	1

ChEMBL screening assays

78 unique, capped per target: 53 binding, 25 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075344	Functional	TP_TRANSPORTER: inhibition of Taurocholate uptake (Taurochorate: 10 uM, CDCA: 100 uM) in Xenopus laevis oocytes	Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. — J Clin Invest
CHEMBL4350134	Binding	Substrate activity at human NTCP expressed in HEK293 cells harboring pEGFP assessed as increase in active uptake at 400 uM measured for 30 mins in presence of sodium chloride by UPLC-MS/MS analysis	Synthesis, pharmacological evaluation, and mechanistic study of adefovir mixed phosphonate derivatives bearing cholic acid and l-amino acid moieties for the treatment of HBV. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C9B9	HepG2-NTCP1	Cancer cell line	Male
CVCL_C9BA	HepG2-NTCP1 HBV	Cancer cell line	Male
CVCL_C9BB	HepG2-NTCP1 HBV Cas9	Cancer cell line	Male
CVCL_JA65	NtG20.i7	Cancer cell line	Male
CVCL_JY39	HepaRG-hNTCP	Cancer cell line	Female
CVCL_JY40	HepG2-hNTCP	Cancer cell line	Male
CVCL_ZW90	HuH-7-END	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.