SOAT1
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Also known as ACATACAT1
Summary
SOAT1 (sterol O-acyltransferase 1, HGNC:11177) is a protein-coding gene on chromosome 1q25.2, encoding Sterol O-acyltransferase 1 (P35610). Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol.
The protein encoded by this gene belongs to the acyltransferase family. It is located in the endoplasmic reticulum, and catalyzes the formation of fatty acid-cholesterol esters. This gene has been implicated in the formation of beta-amyloid and atherosclerotic plaques by controlling the equilibrium between free cholesterol and cytoplasmic cholesteryl esters. Alternatively spliced transcript variants have been found for this gene.
Source: NCBI Gene 6646 — RefSeq curated summary.
At a glance
- Gene–disease (curated): beta-ketothiolase deficiency (Definitive, ClinGen)
- GWAS associations: 3
- Clinical variants (ClinVar): 932 total — 98 pathogenic, 79 likely-pathogenic
- Druggable target: yes — 6 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_003101
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:11177 |
| Approved symbol | SOAT1 |
| Name | sterol O-acyltransferase 1 |
| Location | 1q25.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | ACAT, ACAT1 |
| Ensembl gene | ENSG00000057252 |
| Ensembl biotype | protein_coding |
| OMIM | 102642 |
| Entrez | 6646 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 13 protein_coding
ENST00000367619, ENST00000426956, ENST00000539888, ENST00000540564, ENST00000904812, ENST00000904813, ENST00000904814, ENST00000904815, ENST00000928394, ENST00000961795, ENST00000961796, ENST00000961797, ENST00000961798
RefSeq mRNA: 3 — MANE Select: NM_003101
NM_001252511, NM_001252512, NM_003101
CCDS: CCDS1330, CCDS58047, CCDS58048
Canonical transcript exons
ENST00000367619 — 16 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000522292 | 179350296 | 179350431 |
| ENSE00000922012 | 179344947 | 179345076 |
| ENSE00000922014 | 179348844 | 179348942 |
| ENSE00001068524 | 179342114 | 179342192 |
| ENSE00001068526 | 179342862 | 179342943 |
| ENSE00001068529 | 179343590 | 179343635 |
| ENSE00001160977 | 179347600 | 179347697 |
| ENSE00001165663 | 179351317 | 179351462 |
| ENSE00001199033 | 179353585 | 179358680 |
| ENSE00001350391 | 179293797 | 179293936 |
| ENSE00003467167 | 179323437 | 179323495 |
| ENSE00003621111 | 179337837 | 179337896 |
| ENSE00003633477 | 179302677 | 179302802 |
| ENSE00003664429 | 179339438 | 179339545 |
| ENSE00003694604 | 179335506 | 179335657 |
| ENSE00003787334 | 179341028 | 179341310 |
Expression profiles
Bgee: expression breadth ubiquitous, 266 present calls, max score 99.35.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.2381 / max 673.9950, expressed in 1819 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 6906 | 46.8780 | 1818 |
| 6905 | 3.2086 | 1405 |
| 6907 | 0.1514 | 52 |
Top tissues by expression
285 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| adrenal tissue | UBERON:0018303 | 99.35 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 97.96 | gold quality |
| right adrenal gland | UBERON:0001233 | 97.54 | gold quality |
| adrenal cortex | UBERON:0001235 | 97.37 | gold quality |
| adrenal gland | UBERON:0002369 | 97.08 | gold quality |
| left adrenal gland | UBERON:0001234 | 97.05 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 97.05 | gold quality |
| upper leg skin | UBERON:0004262 | 96.72 | gold quality |
| parotid gland | UBERON:0001831 | 95.27 | gold quality |
| bronchial epithelial cell | CL:0002328 | 94.30 | gold quality |
| endothelial cell | CL:0000115 | 93.84 | gold quality |
| visceral pleura | UBERON:0002401 | 93.14 | gold quality |
| monocyte | CL:0000576 | 93.06 | gold quality |
| mononuclear cell | CL:0000842 | 92.57 | gold quality |
| leukocyte | CL:0000738 | 92.30 | gold quality |
| islet of Langerhans | UBERON:0000006 | 91.79 | gold quality |
| ventricular zone | UBERON:0003053 | 91.55 | gold quality |
| stromal cell of endometrium | CL:0002255 | 90.42 | gold quality |
| parietal pleura | UBERON:0002400 | 90.25 | gold quality |
| pleura | UBERON:0000977 | 90.16 | gold quality |
| mammalian vulva | UBERON:0000997 | 89.78 | gold quality |
| calcaneal tendon | UBERON:0003701 | 89.61 | gold quality |
| gall bladder | UBERON:0002110 | 89.32 | gold quality |
| colonic epithelium | UBERON:0000397 | 88.67 | gold quality |
| mucosa of paranasal sinus | UBERON:0005030 | 88.23 | gold quality |
| lower lobe of lung | UBERON:0008949 | 87.84 | gold quality |
| epithelium of bronchus | UBERON:0002031 | 87.80 | gold quality |
| bronchus | UBERON:0002185 | 87.43 | gold quality |
| caput epididymis | UBERON:0004358 | 87.42 | gold quality |
| pancreas | UBERON:0001264 | 87.16 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 9.88 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CEBPA
miRNA regulators (miRDB)
162 targeting SOAT1, 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-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-3689D | 100.00 | 66.14 | 1181 |
| HSA-MIR-6851-5P | 100.00 | 65.63 | 1294 |
| HSA-MIR-4262 | 100.00 | 73.26 | 3931 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-1252-5P | 100.00 | 69.80 | 2774 |
| HSA-MIR-513A-5P | 100.00 | 69.77 | 2465 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-181A-5P | 99.99 | 72.96 | 2995 |
| HSA-MIR-181B-5P | 99.99 | 72.97 | 2996 |
| HSA-MIR-181C-5P | 99.99 | 72.95 | 2996 |
| HSA-MIR-181D-5P | 99.99 | 73.04 | 2997 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-MIR-548P | 99.98 | 72.25 | 3784 |
| HSA-MIR-607 | 99.97 | 73.62 | 5593 |
| HSA-MIR-548AJ-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548X-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-495-3P | 99.96 | 72.81 | 4197 |
| HSA-MIR-5688 | 99.96 | 73.23 | 4504 |
| HSA-MIR-3658 | 99.96 | 73.87 | 4379 |
| HSA-MIR-4666A-3P | 99.96 | 71.71 | 3434 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-1468-3P | 99.96 | 72.74 | 3797 |
| HSA-MIR-570-3P | 99.96 | 72.41 | 4910 |
| HSA-MIR-548J-3P | 99.94 | 72.61 | 4881 |
| HSA-MIR-651-3P | 99.94 | 73.48 | 5177 |
Literature-anchored findings (GeneRIF, showing 40)
- allosteric activation by cholesterol (PMID:12533546)
- polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1) is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load and with low cerebrospinal fluid levels of cholesterol (PMID:12851640)
- ACAT-1 transcripts predominate in human liver and ACAT-2 transcripts predominate in human duodenum and support the notion that ACAT-2 has an important regulatory role in liver and intestine. (PMID:14729857)
- expression in monocytes infiltrating from the circulation to vascular walls may be enhanced by pre-existing transforming growth factor-beta1 (PMID:15219857)
- A stable upstream stem-loop structure enhances selection of the first 5’-ORF-AUG as a main start codon for translation initiation of ACAT1 mRNA. (PMID:15253151)
- increasing DGAT1, ACAT1, or ACAT2 expression stimulates the assembly and secretion of VLDL from liver cells (PMID:15308631)
- a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by dexamethasone could be functionally bound with glucocorticoid receptor (GR) proteins. (PMID:15353128)
- The results of a comprehensive genetic assessment of SOAT1 variants in the NIMH AD Genetics Initiative study sample are presented. (PMID:15768051)
- Disulfide linkage map shows that cysteine(C)92 is located on the cytoplasmic side of the endoplasmic reticulum (ER) membrane and the disulfide is located in the ER lumen, while all other free Cs are located within the hydrophobic region(s) of the enzyme. (PMID:15850387)
- The structural features of various sterols as substrates and/or activators of ACAT1 and ACAT2 in vitro are reported. (PMID:15992359)
- Our results indicate that the polymorphism rs1044925 in the 3’UTR of SOAT1 gene does not affect the risk of SAD in the northern Han-Chinese. (PMID:16043284)
- results led us to construct a revised, nine-transmembrane domain model, with the active site His-460 located within a hitherto undisclosed transmembrane domain, between Arg-443 and Tyr-462 (PMID:16154994)
- Serum-induced depletion of cellular cholesterol available for esterification by ACAT was a strong, independent predictor of major adverse cardiovascular events and death. (PMID:16230498)
- The new ACAT inhibitor VULM1457 in concentration 0.03 and 0.1 micromol/l significantly down-regulated specific AM receptors on HepG2 cells, reduced AM secretion of HepG2 cells exposed to hypoxia. (PMID:16474185)
- histidine residues located at the active site are very crucial both for the catalytic activity of the enzyme and for distinguishing ACAT1 from ACAT2 with respect to enzyme catalysis and substrate specificity (PMID:16647063)
- These data show that even a modest decrease in ACAT activity can have robust suppressive effects on Abeta generation. (PMID:17412327)
- Our study confirmed cognitive decline and highly frequent delirium after bypass heart surgery and excluded the possible role of SOAT-1 genotype polymorphisms in their genesis (PMID:17593314)
- SOAT1 gene may possibly be only a minor risk factor in Alzheimer’s disease (PMID:17622762)
- Several residues in one subunit closely interact with the same residues in the other subunit; mutating these res. to Cys does not lead to loss in enzyme activity. Mutating residues F453, A457, or H460 to Cys causes large loss in enzyme activity. (PMID:17691824)
- increase in the in vitro ACAT1 activity in PC-3 prostate cancer cells treated with androgen (PMID:18000807)
- In clear cell type renal cell carcinoma upregulation of ACAT-1 leads to high ACAT enzymatic activity, which accelerates the accumulation of cholesterol ester. (PMID:18269457)
- The results suggest that rs1044925 polymorphism in ACAT1 gene is not only associated with serum LDL-C and nHDLC levels in healthy Chinese subjects in Chengdu area, but also with HDL-C level in subjects with endogenous hypertriglyceridemia. (PMID:18393248)
- RNA secondary structures located in the vicinity of the GGC(1274-1276) codon are required for production of the 56-kDa isoform. (PMID:18542101)
- ACAT inhibition may stimulate cholesterol-catabolic (cytochrome P450) pathway in lesion-macrophages. (PMID:18779653)
- Angiotensin II enhances foam cell formation by upregulating ACAT1 expression predominantly through the actions of AT(1) receptor via the G protein/c-Src/PKC/MAPK pathway in human monocyte-macrophages (PMID:18971559)
- Docosahexaenoic acid can act as a substrate for ACAT1. In the manner of a poor substrate, docosahexaenoic acid also inhibited the activity of ACAT1. (PMID:19217763)
- Results suggest that the ERK, p38MAPK and JNK signaling pathways may be involved in insulin-mediated regulation of ACAT1, but no PI3K and PLC-gamma signaling pathways were involved in the present study. (PMID:19269342)
- Results show that signaling through ACAT/cholesterol esterification is a novel pathway for the CCK2R that contributes to tumor cell proliferation and invasion. (PMID:19502590)
- Leptin accelerates cholesteryl ester accumulation in human monocyte-derived macrophages by increasing ACAT-1 expression. (PMID:19625677)
- High ACAT1 expression is associated with estrogen receptor negative basal-like breast cancer. (PMID:19851860)
- Macrophages cope with cholesterol loading by using a novel mechanism: they produce more ER-derived vesicles with elevated ACAT1 enzyme activity without having to produce more ACAT1 protein. (PMID:20460577)
- the plaque-modulating effects of K-604 can be explained by stimulation of procollagen production independent of ACAT inhibition in addition to potent inhibition of macrophage ACAT-1 (PMID:20843517)
- Visfatin may down-regulate the ABCA1 expression and up-regulate the ACAT1 expression via PPARgamma signal transduction pathway, which decreases the outflow of free cholesterol, increases the content of cholesterol esters, and then induces foam cell formation. (PMID:20945045)
- the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum total cholesterol, LDL-C and ApoB levels in the Bai Ku Yao population (PMID:21143839)
- In THP-1-derived macrophages and foam cells, the expression level of ACAT-1 and cellular cholesterol content increased significantly in response to asymmetric dimethylarginine treatment in a time- and concentration-dependent manner. (PMID:21177161)
- SF-1-dependent up-regulation of SOAT1 may be important for maintaining readily-releasable cholesterol reserves needed for active steroidogenesis and during episodes of recurrent stress. (PMID:21239516)
- These findings suggest the potential involvement of MAPK and STAT pathways in norcantharidin-induced apoptogenesis. (PMID:21266192)
- These studies demonstrate that both SIAE and SOAT activities seem to be responsible for the enhanced level of Neu5,9Ac(2) in lymphoblasts, which is a hallmark in acute lymphoblastic leukemia (PMID:21803834)
- The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum total cholesterol, HDL-cholesterol and ApoAI levels than the C allele noncarriers. (PMID:22243772)
- Essential oil of Pinus koraiensis leaves significantly inhibited hACAT1 levels in HepG2 cells. (PMID:22275303)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | soat1 | ENSDARG00000062297 |
| mus_musculus | Soat1 | ENSMUSG00000026600 |
| rattus_norvegicus | Soat1 | ENSRNOG00000004111 |
| drosophila_melanogaster | CG8112 | FBGN0037612 |
| caenorhabditis_elegans | WBGENE00007174 |
Paralogs (2): SOAT2 (ENSG00000167780), DGAT1 (ENSG00000185000)
Protein
Protein identifiers
Sterol O-acyltransferase 1 — P35610 (reviewed: P35610)
Alternative names: Acyl-coenzyme A:cholesterol acyltransferase 1, Cholesterol acyltransferase 1
All UniProt accessions (2): P35610, B1APM4
UniProt curated annotations — full annotation on UniProt →
Function. Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. Preferentially utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) as a substrate: shows a higher activity towards an acyl-CoA substrate with a double bond at the delta-9 position (9Z) than towards saturated acyl-CoA or an unsaturated acyl-CoA with a double bond at the delta-7 (7Z) or delta-11 (11Z) positions.
Subunit / interactions. Homotetramer; composed of two homodimers. Interacts with UBIAD1.
Subcellular location. Endoplasmic reticulum membrane.
Activity regulation. Cholesterol O-acyltransferase activity is inhibited by nevanimibe.
Domain organisation. Each protomer consists of 9 transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site: acyl-CoA enters the active site through the cytosolic tunnel, whereas cholesterol enters from the side through the transmembrane tunnel.
Induction. Highly activated by the presence of cholesterol.
Similarity. Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P35610-1 | 1 | yes |
| P35610-2 | 2 | |
| P35610-3 | 3 |
RefSeq proteins (3): NP_001239440, NP_001239441, NP_003092* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR004299 | MBOAT_fam | Family |
| IPR014371 | Oat_ACAT_DAG_ARE | Family |
| IPR030687 | Sterol_acyltranf_meta | Family |
Pfam: PF03062
Enzyme classification (BRENDA):
- EC 2.3.1.26 — sterol O-acyltransferase (BRENDA: 24 organisms, 85 substrates, 472 inhibitors, 32 Km, 0 kcat entries)
Substrate kinetics (BRENDA)
8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| OLEOYL-COA | 0.0013–0.069 | 12 |
| CIS-9-OCTADECENOYL-COA | — | 6 |
| CHOLESTEROL | 0.0016–0.06 | 2 |
| ELAIDOYL-COA | 0.0022 | 1 |
| LINOLEOYL-COA | 0.0028 | 1 |
| PALMITOYL-COA | 0.038 | 1 |
| PREGNENOLONE | 0.0012 | 1 |
| STEAROYL-COA | 0.0064 | 1 |
Catalyzed reactions (Rhea), 10 shown:
- an acyl-CoA + cholesterol = a cholesterol ester + CoA (RHEA:17729)
- cholesterol + (9Z)-octadecenoyl-CoA = cholesteryl (9Z-octadecenoate) + CoA (RHEA:41436)
- cholesterol + hexadecanoyl-CoA = cholesteryl hexadecanoate + CoA (RHEA:42792)
- (9Z,12Z)-octadecadienoyl-CoA + cholesterol = cholesteryl (9Z,12Z)-octadecadienoate + CoA (RHEA:42796)
- octadecanoyl-CoA + cholesterol = cholesteryl octadecanoate + CoA (RHEA:42812)
- (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + cholesterol = cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA (RHEA:42816)
- a sterol + a long-chain fatty acyl-CoA = a long-chain 3-hydroxysterol ester + CoA (RHEA:59816)
- (9Z)-hexadecenoyl-CoA + cholesterol = cholesteryl (9Z)-hexadecenoate + CoA (RHEA:64320)
- (11Z)-octadecenoyl-CoA + cholesterol = cholesteryl (11Z)-octadecenoate + CoA (RHEA:64324)
- (7Z)-octadecenoyl-CoA + cholesterol = cholesteryl (7Z)-octadecenoate + CoA (RHEA:64328)
UniProt features (84 total): mutagenesis site 24, helix 19, topological domain 10, transmembrane region 9, binding site 8, modified residue 2, splice variant 2, strand 2, turn 2, chain 1, region of interest 1, short sequence motif 1, active site 1, disulfide bond 1, sequence variant 1
Structure
Experimental structures (PDB)
5 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6P2J | ELECTRON MICROSCOPY | 3 |
| 6P2P | ELECTRON MICROSCOPY | 3.1 |
| 6L47 | ELECTRON MICROSCOPY | 3.5 |
| 6L48 | ELECTRON MICROSCOPY | 3.5 |
| 6VUM | ELECTRON MICROSCOPY | 3.67 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P35610-F1 | 81.22 | 0.51 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 460
Ligand- & substrate-binding residues (8): 137; 415; 418; 421; 425; 433; 445; 456
Post-translational modifications (2): 1, 8
Disulfide bonds (1): 528–546
Mutagenesis-validated functional residues (24):
| Position | Phenotype |
|---|---|
| 262 | strongly reduced cholesterol o-acyltransferase activity. |
| 263 | strongly reduced cholesterol o-acyltransferase activity. |
| 269 | nearly normal expression and enzyme activity. |
| 269 | no expression nor activity. |
| 306 | strongly reduced cholesterol o-acyltransferase activity. |
| 367 | abolished homodimerization; when associated with 504-a–a-508. |
| 386 | abolished cholesterol o-acyltransferase activity. |
| 400 | low expression, loss of enzymatic activity. |
| 407 | almost abolished cholesterol o-acyltransferase activity. |
| 415 | reduced cholesterol o-acyltransferase activity. |
| 418 | reduced cholesterol o-acyltransferase activity. |
| 420 | almost abolished cholesterol o-acyltransferase activity. |
| 421 | almost abolished cholesterol o-acyltransferase activity. |
| 425 | strongly reduced cholesterol o-acyltransferase activity. |
| 428 | almost abolished cholesterol o-acyltransferase activity. |
| 429 | strongly reduced cholesterol o-acyltransferase activity. |
| 445 | reduced cholesterol o-acyltransferase activity. |
| 452–456 | in qq mutant; almost abolished cholesterol o-acyltransferase activity. |
| 452–453 | almost abolished cholesterol o-acyltransferase activity. |
| 456 | abolished cholesterol o-acyltransferase activity. |
| 460 | abolished cholesterol o-acyltransferase activity. |
| 504–508 | abolished homodimerization; when associated with a-367. |
| 507 | strongly reduced cholesterol o-acyltransferase activity. |
| 518 | loss of enzymatic activity. |
Function
Pathways and Gene Ontology
Reactome pathways
4 pathways
| ID | Pathway |
|---|---|
| R-HSA-8964038 | LDL clearance |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance |
| R-HSA-382551 | Transport of small molecules |
| R-HSA-8964043 | Plasma lipoprotein clearance |
MSigDB gene sets: 637 (showing top):
GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, AHRARNT_01, GOBP_LIPID_MODIFICATION, E2F_Q4, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_METANEPHROS_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, GOBP_STEROL_HOMEOSTASIS, GOBP_METANEPHRIC_EPITHELIUM_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GOBP_COENZYME_A_METABOLIC_PROCESS
GO Biological Process (10): cholesterol metabolic process (GO:0008203), macrophage derived foam cell differentiation (GO:0010742), cholesterol storage (GO:0010878), cholesterol efflux (GO:0033344), very-low-density lipoprotein particle assembly (GO:0034379), low-density lipoprotein particle clearance (GO:0034383), cholesterol homeostasis (GO:0042632), positive regulation of amyloid precursor protein biosynthetic process (GO:0042986), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)
GO Molecular Function (9): fatty-acyl-CoA binding (GO:0000062), sterol O-acyltransferase activity (GO:0004772), cholesterol binding (GO:0015485), cholesterol O-acyltransferase activity (GO:0034736), identical protein binding (GO:0042802), protein binding (GO:0005515), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)
GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-3 pathways:
| Category | Pathways |
|---|---|
| Plasma lipoprotein clearance | 1 |
| Transport of small molecules | 1 |
| Plasma lipoprotein assembly, remodeling, and clearance | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| sterol metabolic process | 1 |
| secondary alcohol metabolic process | 1 |
| foam cell differentiation | 1 |
| lipid storage | 1 |
| cholesterol transport | 1 |
| plasma lipoprotein particle assembly | 1 |
| plasma lipoprotein particle clearance | 1 |
| low-density lipoprotein particle disassembly | 1 |
| sterol homeostasis | 1 |
| positive regulation of glycoprotein biosynthetic process | 1 |
| amyloid precursor protein biosynthetic process | 1 |
| regulation of amyloid precursor protein biosynthetic process | 1 |
| primary metabolic process | 1 |
| lipid metabolic process | 1 |
| acyl-CoA binding | 1 |
| fatty acid derivative binding | 1 |
| acyltransferase activity, transferring groups other than amino-acyl groups | 1 |
| sterol binding | 1 |
| alcohol binding | 1 |
| sterol O-acyltransferase activity | 1 |
| protein binding | 1 |
| binding | 1 |
| catalytic activity | 1 |
| transferase activity | 1 |
| cytoplasm | 1 |
| endomembrane system | 1 |
| intracellular membrane-bounded organelle | 1 |
| organelle membrane | 1 |
| nuclear outer membrane-endoplasmic reticulum membrane network | 1 |
| endoplasmic reticulum subcompartment | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
1758 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| SOAT1 | VPS52 | Q8N1B4 | 792 |
| SOAT1 | SCARB1 | Q8WTV0 | 684 |
| SOAT1 | HMGCR | P04035 | 684 |
| SOAT1 | NCEH1 | Q6PIU2 | 665 |
| SOAT1 | ABCA1 | O95477 | 613 |
| SOAT1 | UBIAD1 | Q9Y5Z9 | 591 |
| SOAT1 | ABCG1 | P45844 | 574 |
| SOAT1 | CES1 | P23141 | 570 |
| SOAT1 | SQLE | Q14534 | 553 |
| SOAT1 | LCAT | P04180 | 552 |
| SOAT1 | SREBF2 | Q12772 | 552 |
| SOAT1 | APOE | P02649 | 513 |
| SOAT1 | SCAP | Q12770 | 491 |
| SOAT1 | CYP46A1 | Q9Y6A2 | 490 |
| SOAT1 | DGAT2 | Q96PD7 | 487 |
IntAct
180 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| HRAS | RAF1 | psi-mi:“MI:0914”(association) | 0.980 |
| NRAS | RAF1 | psi-mi:“MI:0914”(association) | 0.930 |
| ENTREP1 | WWP2 | psi-mi:“MI:0914”(association) | 0.850 |
| RAB11A | EVI5 | psi-mi:“MI:0914”(association) | 0.800 |
| ERLIN1 | ERLIN2 | psi-mi:“MI:0914”(association) | 0.740 |
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| HRAS | RGL2 | psi-mi:“MI:0914”(association) | 0.660 |
| CANX | SOAT1 | psi-mi:“MI:0403”(colocalization) | 0.610 |
| SOAT1 | CARNMT1 | psi-mi:“MI:0915”(physical association) | 0.590 |
| ADGRG5 | KLRG2 | psi-mi:“MI:0914”(association) | 0.530 |
| SEMA7A | SGPL1 | psi-mi:“MI:0914”(association) | 0.530 |
| LYPD6 | PLXNB2 | psi-mi:“MI:0914”(association) | 0.530 |
| TMPRSS12 | FZD6 | psi-mi:“MI:0914”(association) | 0.530 |
| PEX19 | FAM20B | psi-mi:“MI:0914”(association) | 0.530 |
| ADAM33 | LRP5 | psi-mi:“MI:0914”(association) | 0.530 |
| SMPD3 | ENDOD1 | psi-mi:“MI:0914”(association) | 0.530 |
| ASGR2 | MT-CO1 | psi-mi:“MI:0914”(association) | 0.530 |
| FAM187B | HSPA5 | psi-mi:“MI:0914”(association) | 0.530 |
| RTN4R | SOAT1 | psi-mi:“MI:0914”(association) | 0.530 |
| TSPAN5 | SC5D | psi-mi:“MI:0914”(association) | 0.530 |
| APOC2 | APOE | psi-mi:“MI:0914”(association) | 0.530 |
BioGRID (389): SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Affinity Capture-MS), SOAT1 (Proximity Label-MS), SOAT1 (Proximity Label-MS), SOAT1 (Proximity Label-MS), SOAT1 (Proximity Label-MS), SOAT1 (Proximity Label-MS), SOAT1 (Proximity Label-MS)
ESM2 similar proteins: A0A078H868, A0AAS4, A0JP80, A6X919, D4AD75, O70536, O77760, O77761, P23913, P35610, P53439, P56079, Q14739, Q20696, Q20735, Q28677, Q2PZI1, Q4JM44, Q4R763, Q5R7H4, Q5RK27, Q60457, Q61263, Q63632, Q63633, Q657W3, Q6AX73, Q6Z0E2, Q7T3T4, Q7TSX5, Q86VZ5, Q8IWX5, Q8NHU3, Q8VCQ6, Q91V14, Q924N4, Q965Q4, Q9D4B1, Q9FJB4, Q9H2X9
Diamond homologs: A0A0P0WY03, A0A161IUT7, I1MSF2, K7LC65, O70536, O75907, O75908, O77759, O77760, O77761, O88908, P25628, P35610, P53629, P84285, Q55BH9, Q5GKZ7, Q5I396, Q60457, Q61263, Q7TQM4, Q876L2, Q876L3, Q8MK44, Q9ERM3, Q9GMF1, Q9SLD2, Q9Z2A7, Q9UU82, Q10269
SIGNOR signaling
3 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| Avasimibe | down-regulates | SOAT1 | “chemical inhibition” |
| cholesterol | “up-regulates activity” | SOAT1 | “chemical activation” |
| SOAT1 | “down-regulates quantity” | “cholesteryl ester” | “chemical modification” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 218 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Signaling by FGFR1 in disease | 6 | 12.5× | 2e-03 |
| RHOQ GTPase cycle | 7 | 9.0× | 2e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| cholesterol transport | 5 | 20.1× | 6e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
932 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 98 |
| Likely pathogenic | 79 |
| Uncertain significance | 230 |
| Likely benign | 324 |
| Benign | 63 |
Top pathogenic / likely-pathogenic (30)
| Variant ID | HGVS | Classification |
|---|---|---|
| 1069757 | NM_000019.4(ACAT1):c.1173dup (p.Ala392fs) | Pathogenic |
| 1073055 | NM_000019.4(ACAT1):c.233del (p.Lys78fs) | Pathogenic |
| 1076202 | NM_000019.4(ACAT1):c.1100T>A (p.Leu367Ter) | Pathogenic |
| 1076974 | NC_000011.9:g.(?107992324)(107992415_?)del | Pathogenic |
| 1172774 | NM_000019.4(ACAT1):c.252del (p.Glu85fs) | Pathogenic |
| 1172775 | NM_000019.4(ACAT1):c.1117A>T (p.Lys373Ter) | Pathogenic |
| 1332739 | NM_000019.4(ACAT1):c.731-2A>G | Pathogenic |
| 1367924 | NC_000011.9:g.(?108005849)(108005989_?)del | Pathogenic |
| 1374250 | NM_000019.4(ACAT1):c.316C>T (p.Gln106Ter) | Pathogenic |
| 1384281 | NM_000019.4(ACAT1):c.846dup (p.Ala283fs) | Pathogenic |
| 1426396 | NM_000019.4(ACAT1):c.1189C>A (p.His397Asn) | Pathogenic |
| 1449779 | NM_000019.4(ACAT1):c.826+2T>C | Pathogenic |
| 1452347 | NM_000019.4(ACAT1):c.655_656insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGCTATTAATTCTT (p.Tyr219delinsPhePhePhePhePhePhePheXaaXaaXaaXaaTrpSerArgSerProAspLeuMetIleHisProProArgProProLysValLeuGlyLeuGlnAlaTer) | Pathogenic |
| 1454055 | NM_000019.4(ACAT1):c.763G>T (p.Glu255Ter) | Pathogenic |
| 1459346 | NC_000011.9:g.(?108010782)(108012437_?)del | Pathogenic |
| 147281 | GRCh38/hg38 11q22.3(chr11:107479091-108222532)x1 | Pathogenic |
| 1705360 | NM_000019.4(ACAT1):c.433C>T (p.Gln145Ter) | Pathogenic |
| 193787 | NM_000019.4(ACAT1):c.1006-4_1006-1delinsAAA | Pathogenic |
| 1991943 | NM_000019.4(ACAT1):c.649_652dup (p.Ser218Ter) | Pathogenic |
| 2001273 | NM_000019.4(ACAT1):c.330dup (p.Ala111fs) | Pathogenic |
| 2003666 | NM_000019.4(ACAT1):c.272del (p.Met91fs) | Pathogenic |
| 2011809 | NM_000019.4(ACAT1):c.170del (p.Gly57fs) | Pathogenic |
| 208341 | NM_000019.4(ACAT1):c.149del (p.Thr50fs) | Pathogenic |
| 2099256 | NM_000019.4(ACAT1):c.542_543del (p.Lys181fs) | Pathogenic |
| 2101162 | NM_000019.4(ACAT1):c.75_76del (p.Glu25fs) | Pathogenic |
| 2115197 | NM_000019.4(ACAT1):c.580-93_626del | Pathogenic |
| 2117488 | NM_000019.4(ACAT1):c.104C>G (p.Ser35Ter) | Pathogenic |
| 2127596 | NM_000019.4(ACAT1):c.835del (p.Thr279fs) | Pathogenic |
| 2169323 | NM_001386678.1(ACAT1):c.120+2267_120+2268del | Pathogenic |
| 225062 | NM_000019.4(ACAT1):c.757G>A (p.Asp253Asn) | Pathogenic |
SpliceAI
3645 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 11:108128830:G:GT | donor_gain | 1.0000 |
| 11:108128835:GGCTT:G | donor_gain | 1.0000 |
| 11:108128850:G:GT | donor_gain | 1.0000 |
| 11:108128861:C:G | donor_gain | 1.0000 |
| 11:108131901:TTACA:T | acceptor_loss | 1.0000 |
| 11:108131902:TACAG:T | acceptor_loss | 1.0000 |
| 11:108131904:CAG:C | acceptor_loss | 1.0000 |
| 11:108131905:A:AG | acceptor_gain | 1.0000 |
| 11:108131905:A:G | acceptor_loss | 1.0000 |
| 11:108131905:AG:A | acceptor_gain | 1.0000 |
| 11:108131906:G:A | acceptor_loss | 1.0000 |
| 11:108131906:G:GA | acceptor_gain | 1.0000 |
| 11:108131906:GG:G | acceptor_gain | 1.0000 |
| 11:108131906:GGA:G | acceptor_gain | 1.0000 |
| 11:108131906:GGAA:G | acceptor_gain | 1.0000 |
| 11:108131951:GAAG:G | donor_gain | 1.0000 |
| 11:108131953:AG:A | donor_gain | 1.0000 |
| 11:108131954:GG:G | donor_gain | 1.0000 |
| 11:108131954:GGT:G | donor_loss | 1.0000 |
| 11:108131955:G:GG | donor_gain | 1.0000 |
| 11:108131955:GTAA:G | donor_loss | 1.0000 |
| 11:108134217:AAAG:A | acceptor_gain | 1.0000 |
| 11:108134217:AAAGG:A | acceptor_gain | 1.0000 |
| 11:108134301:G:GT | donor_gain | 1.0000 |
| 11:108138882:T:TA | acceptor_gain | 1.0000 |
| 11:108138883:G:A | acceptor_gain | 1.0000 |
| 11:108138891:T:A | acceptor_gain | 1.0000 |
| 11:108138893:C:CA | acceptor_gain | 1.0000 |
| 11:108138896:A:AG | acceptor_gain | 1.0000 |
| 11:108138896:A:G | acceptor_loss | 1.0000 |
AlphaMissense
3646 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:179348850:T:A | W408R | 1.000 |
| 1:179348850:T:C | W408R | 1.000 |
| 1:179347690:T:C | F403S | 0.999 |
| 1:179348847:T:A | W407R | 0.999 |
| 1:179348847:T:C | W407R | 0.999 |
| 1:179348852:G:C | W408C | 0.999 |
| 1:179348852:G:T | W408C | 0.999 |
| 1:179348886:T:A | W420R | 0.999 |
| 1:179348886:T:C | W420R | 0.999 |
| 1:179348891:T:A | N421K | 0.999 |
| 1:179348891:T:G | N421K | 0.999 |
| 1:179348907:T:A | W427R | 0.999 |
| 1:179348907:T:C | W427R | 0.999 |
| 1:179351376:T:A | W504R | 0.999 |
| 1:179351376:T:C | W504R | 0.999 |
| 1:179342913:C:A | P304H | 0.998 |
| 1:179342928:G:C | R309P | 0.998 |
| 1:179347674:T:C | F398L | 0.998 |
| 1:179347676:T:A | F398L | 0.998 |
| 1:179347676:T:G | F398L | 0.998 |
| 1:179347680:G:C | D400H | 0.998 |
| 1:179347689:T:C | F403L | 0.998 |
| 1:179347691:C:A | F403L | 0.998 |
| 1:179347691:C:G | F403L | 0.998 |
| 1:179348851:G:C | W408S | 0.998 |
| 1:179348911:T:C | L428P | 0.998 |
| 1:179350338:T:C | F453L | 0.998 |
| 1:179350340:T:A | F453L | 0.998 |
| 1:179350340:T:G | F453L | 0.998 |
| 1:179350351:C:A | A457D | 0.998 |
dbSNP variants (sampled 300 via entrez): RS1000039288 (1:179315359 G>A), RS1000042421 (1:179338418 C>G), RS1000066189 (1:179321877 T>C), RS1000109723 (1:179343319 G>T), RS1000177625 (1:179350208 C>T), RS1000212514 (1:179301606 G>A), RS1000279920 (1:179306520 T>C), RS1000325527 (1:179345442 A>G,T), RS1000355987 (1:179302984 T>A), RS1000394663 (1:179357351 T>C), RS1000401571 (1:179313174 G>A,C), RS1000463421 (1:179357168 G>A), RS1000482391 (1:179298574 T>C,G), RS1000510911 (1:179305524 A>G,T), RS1000514612 (1:179298808 T>G)
Disease associations
OMIM: gene MIM:102642 | disease phenotypes: MIM:203750, MIM:208900
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| beta-ketothiolase deficiency | Definitive | Autosomal recessive |
ClinGen Gene-Disease Validity (1)
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
| Disease | Classification | Inheritance |
|---|---|---|
| beta-ketothiolase deficiency | Definitive | AR |
Mondo (3): beta-ketothiolase deficiency (MONDO:0008760), ataxia telangiectasia (MONDO:0008840), primary ovarian failure (MONDO:0005387)
Orphanet (3): Beta-ketothiolase deficiency (Orphanet:134), Ataxia-telangiectasia (Orphanet:100), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST007250_11 | Nonunion in individuals with fractures | 3.000000e-07 |
| GCST009391_1527 | Metabolite levels | 6.000000e-06 |
| GCST010002_248 | Refractive error | 4.000000e-19 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0009707 | fractures, ununited |
| EFO:0009771 | methionine measurement |
MeSH disease descriptors (3)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D001260 | Ataxia Telangiectasia | C10.228.140.252.190.530.060; C10.562.100; C10.597.350.090.500.530.060; C14.907.823.213; C16.320.080; C16.320.798.250; C18.452.284.060; C20.673.795.250 |
| D016649 | Primary Ovarian Insufficiency | C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750 |
| C535434 | Beta ketothiolase deficiency (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL2782 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 173,103 (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 |
|---|---|---|---|
| CHEMBL103 | PROGESTERONE | 4 | 162,141 |
| CHEMBL101309 | AVASIMIBE | 2 | 10,153 |
| CHEMBL1908306 | EFLUCIMIBE | 2 | 272 |
| CHEMBL46423 | NEVANIMIBE | 2 | 78 |
| CHEMBL478858 | PACTIMIBE | 2 | 260 |
| CHEMBL4297354 | AZD-7687 | 1 | 199 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
Binding affinities (BindingDB)
44 measured of 46 human assays (46 total across all organisms); most potent 44 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| [4-[2-benzyl-5-[2,6-di(propan-2-yl)anilino]-3,5-dioxopentyl]phenyl] 2-(2-oxoazepan-1-yl)acetate | IC50 | 3.2 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| [4-[2-benzyl-5-[2,6-di(propan-2-yl)anilino]-3,5-dioxopentyl]phenyl] 7-(2-oxoazepan-1-yl)heptanoate | IC50 | 3.6 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| 4-benzyl-N-[2,6-di(propan-2-yl)phenyl]-3-oxo-5-phenylpentanamide | IC50 | 4.2 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| 4-benzyl-N-[2,6-di(propan-2-yl)phenyl]-5-(4-hydroxyphenyl)-3-oxopentanamide | IC50 | 10.3 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| 2-[4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)cyclohexyl]acetic acid | IC50 | 15 nM | |
| 2-[4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octan-1-yl]acetic acid | IC50 | 15 nM | |
| 4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octane-1-carboxylic acid | IC50 | 28 nM | |
| 2-[4-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[2.2.2]octan-1-yl]propanoic acid | IC50 | 28 nM | |
| (2S)-2-dodecylsulfanyl-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-phenylacetamide | IC50 | 39 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| 2-[5-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)bicyclo[3.2.2]nonan-1-yl]acetic acid | IC50 | 69 nM | |
| 2-[3-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)adamantan-1-yl]acetic acid | IC50 | 120 nM | |
| 3-(4-{4-amino-7,7-dimethyl-7H-pyrimido[4,5-b][1,4]oxazin-6-yl}phenyl)adamantane-1-carboxylic acid | IC50 | 250 nM | |
| 2-[4-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]acetamide | IC50 | 450 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | IC50 | 600 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| (3R,6S,9S,13S)-9-benzyl-3-[(2S)-butan-2-yl]-13-[(2S)-hexan-2-yl]-6-methyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | IC50 | 900 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| [2-[(5aS,6S,8S,9aR)-6-(4-cyanobenzoyl)oxy-5a-methyl-1,10-dioxo-3-pyridin-3-yl-7,8,9,9a-tetrahydro-6H-pyrano[4,3-b]chromen-8-yl]-2-hydroxypropyl] 4-cyanobenzoate | IC50 | 17800 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| 1-[(1,3-diphenylpyrazol-5-yl)amino]decan-2-one | IC50 | 23000 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| N-(1,3-diphenylpyrazol-5-yl)nonanamide | IC50 | 23000 nM | US-12419847: Composition and method for attenuating neuroinflammation, amyloidopathy and tauopathy |
| 1-[(1,3-diphenylpyrazol-5-yl)amino]nonan-2-one | IC50 | 24000 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| N-(1,3-diphenylpyrazol-5-yl)octanamide | IC50 | 24000 nM | US-12419847: Composition and method for attenuating neuroinflammation, amyloidopathy and tauopathy |
| N-decyl-1,3-diphenylpyrazol-5-amine | IC50 | 39000 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| N-nonyl-1,3-diphenylpyrazol-5-amine | IC50 | 39000 nM | US-12419847: Composition and method for attenuating neuroinflammation, amyloidopathy and tauopathy |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 55000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| [(2R)-2-[(5aR,6R,8R,9aR,10R)-6-acetyloxy-10-hydroxy-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-8-yl]-2-acetyloxypropyl] acetate | IC50 | 56700 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(4-methoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 59000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(3,4,5-trimethoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 60000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| N-(2-phenylphenyl)octanamide | IC50 | 61000 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| [(5aS,6S,8S,9aS,10S)-10-acetyloxy-8-(1,2-diacetyloxypropan-2-yl)-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-6-yl] 4-cyanobenzoate | IC50 | 64700 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| N-(2-phenylphenyl)nonanamide | IC50 | 65000 nM | US-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(3,4-dimethoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 66000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| [4-[2-(3,4-dimethoxyphenyl)ethoxy]-3-methoxyphenyl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate | IC50 | 84400 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(4-methoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 87000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| [(2R)-2-[(5aR,6R,8R,9aS,10S)-6-acetyloxy-10-hydroxy-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-8-yl]-2-acetyloxypropyl] acetate | IC50 | 87400 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(4-methylphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 91000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| [2-[(5aS,6S,8S,9aS,10S)-6-acetyloxy-10-hydroxy-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-8-yl]-2-acetyloxypropyl] acetate | IC50 | 108000 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(4-methylphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 111000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-(2-phenylethoxy)phenyl]prop-2-enamide | IC50 | 112000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(4-hydroxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 114000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-(3,4-dihydroxyphenyl)-N-[4-[2-(4-fluorophenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 134000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-(2-phenylethoxy)phenyl]prop-2-enamide | IC50 | 136000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(4-fluorophenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 152000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| [2-[(5aS,6S,8S,9aR)-6-hydroxy-5a-methyl-1,10-dioxo-3-pyridin-3-yl-7,8,9,9a-tetrahydro-6H-pyrano[4,3-b]chromen-8-yl]-2-hydroxypropyl] 4-cyanobenzoate | IC50 | 154000 nM | US-10278962: Tricyclic analogues, preparation method and uses thereof |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(3,4-dimethoxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 172000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
| (E)-3-[3,4-bis(methoxymethoxy)phenyl]-N-[4-[2-(4-hydroxyphenyl)ethoxy]phenyl]prop-2-enamide | IC50 | 312000 nM | US-20250248955: PHENYL ACRYLIC ACID COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF |
ChEMBL bioactivities
353 potent at pChembl≥5 of 480 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.52 | IC50 | 3 | nM | CHEMBL4281138 |
| 8.49 | IC50 | 3.2 | nM | CHEMBL3936899 |
| 8.44 | IC50 | 3.6 | nM | CHEMBL3899908 |
| 8.38 | IC50 | 4.2 | nM | CHEMBL3894947 |
| 8.15 | IC50 | 7 | nM | CHEMBL4247249 |
| 8.05 | IC50 | 9 | nM | CHEMBL4282905 |
| 8.05 | IC50 | 9 | nM | NEVANIMIBE |
| 8.00 | IC50 | 10 | nM | CHEMBL284596 |
| 7.99 | IC50 | 10.3 | nM | CHEMBL3905226 |
| 7.70 | IC50 | 20 | nM | CHEMBL449307 |
| 7.60 | IC50 | 25 | nM | AVASIMIBE |
| 7.58 | IC50 | 26 | nM | CHEMBL4288347 |
| 7.51 | IC50 | 31 | nM | CHEMBL454397 |
| 7.50 | IC50 | 32 | nM | CHEMBL2397474 |
| 7.50 | IC50 | 32 | nM | CHEMBL449832 |
| 7.50 | IC50 | 32 | nM | CHEMBL453491 |
| 7.46 | IC50 | 35 | nM | CHEMBL459999 |
| 7.46 | IC50 | 35 | nM | CHEMBL33780 |
| 7.46 | IC50 | 35 | nM | CHEMBL304267 |
| 7.44 | IC50 | 36 | nM | CHEMBL304267 |
| 7.43 | IC50 | 37 | nM | CHEMBL500498 |
| 7.41 | IC50 | 39 | nM | EFLUCIMIBE |
| 7.40 | IC50 | 40 | nM | CHEMBL297271 |
| 7.40 | IC50 | 40 | nM | CHEMBL33780 |
| 7.40 | IC50 | 40 | nM | CHEMBL449977 |
| 7.40 | IC50 | 40 | nM | CHEMBL505016 |
| 7.37 | IC50 | 43 | nM | CHEMBL501429 |
| 7.37 | IC50 | 43 | nM | CHEMBL33780 |
| 7.37 | IC50 | 43 | nM | CHEMBL304267 |
| 7.33 | IC50 | 47 | nM | CHEMBL510453 |
| 7.32 | IC50 | 48 | nM | CHEMBL503766 |
| 7.32 | IC50 | 48 | nM | CHEMBL442567 |
| 7.31 | IC50 | 49 | nM | CHEMBL447674 |
| 7.30 | IC50 | 50 | nM | CHEMBL284378 |
| 7.30 | IC50 | 50 | nM | CHEMBL34219 |
| 7.28 | IC50 | 53 | nM | CHEMBL33780 |
| 7.24 | IC50 | 58 | nM | CHEMBL25532 |
| 7.22 | IC50 | 60 | nM | CHEMBL5284960 |
| 7.22 | IC50 | 60 | nM | CHEMBL33054 |
| 7.22 | IC50 | 60 | nM | CHEMBL285429 |
| 7.21 | IC50 | 62 | nM | CHEMBL33780 |
| 7.20 | IC50 | 63 | nM | CHEMBL40685 |
| 7.17 | IC50 | 68 | nM | CHEMBL509834 |
| 7.16 | IC50 | 70 | nM | CHEMBL5275490 |
| 7.16 | IC50 | 69 | nM | CHEMBL33780 |
| 7.16 | IC50 | 70 | nM | CHEMBL286611 |
| 7.16 | IC50 | 70 | nM | CHEMBL33229 |
| 7.12 | IC50 | 75 | nM | CHEMBL30860 |
| 7.12 | IC50 | 75 | nM | CHEMBL286434 |
| 7.11 | IC50 | 77 | nM | CHEMBL443151 |
PubChem BioAssay actives
316 with measured affinity, of 798 total; 50 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-[4-[2-(1,3-benzothiazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]acetamide | 1419341: Inhibition of ACAT in human J774A.1 cells assessed as reduction in esterified-cholesterol accumulation after 18 hrs in presence of 25-hydroxycholesterol by cholesterol E-test analysis | ic50 | 0.0030 | uM |
| 9-(1,3-benzoxazol-2-ylsulfanyl)-N-[2,6-di(propan-2-yl)phenyl]nonanamide | 1419341: Inhibition of ACAT in human J774A.1 cells assessed as reduction in esterified-cholesterol accumulation after 18 hrs in presence of 25-hydroxycholesterol by cholesterol E-test analysis | ic50 | 0.0070 | uM |
| 1-[[1-[4-(dimethylamino)phenyl]cyclopentyl]methyl]-3-[2,6-di(propan-2-yl)phenyl]urea | 1940207: Inhibition of human SOAT1 expressed in mouse AC29 cells | ic50 | 0.0090 | uM |
| 2-[4-[2-(1,3-benzoxazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]acetamide | 1419341: Inhibition of ACAT in human J774A.1 cells assessed as reduction in esterified-cholesterol accumulation after 18 hrs in presence of 25-hydroxycholesterol by cholesterol E-test analysis | ic50 | 0.0090 | uM |
| 1-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-4-(4-methoxyphenyl)piperazine | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0100 | uM |
| (3R,6R,9S,13S)-9-benzhydryl-3-[(2S)-butan-2-yl]-13-[(2S)-hexan-2-yl]-6-methyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | 638437: Inhibition of ACAT1- mediated cholesteryl ester synthesis in macrophages | ic50 | 0.0200 | uM |
| [2,6-di(propan-2-yl)phenyl] N-[2-[2,4,6-tri(propan-2-yl)phenyl]acetyl]sulfamate | 1396730: Inhibition of ACAT1 in human monocytes-derived macrophages reduction in cholesteryl oleate formation preincubated for 2 hrs followed by [14C]-oleic acid/sodium oleate addition measured after 2 hrs in absence of albumin by TLC assay | ic50 | 0.0250 | uM |
| 2-[4-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]acetamide;hydrochloride | 1419341: Inhibition of ACAT in human J774A.1 cells assessed as reduction in esterified-cholesterol accumulation after 18 hrs in presence of 25-hydroxycholesterol by cholesterol E-test analysis | ic50 | 0.0260 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[1-butyl-4-[3-(3-hydroxypropoxy)phenyl]-2-oxo-1,8-naphthyridin-3-yl]urea;hydrate;hydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0310 | uM |
| [(1S,2S)-2-[[2,2-dimethylpropyl(nonyl)carbamoyl]amino]cyclohexyl] 3-[[(4R)-2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl]amino]propanoate | 754945: Inhibition of macrophage ACAT (unknown origin) | ic50 | 0.0320 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-[3-(trifluoromethyl)phenyl]piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0320 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-butoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0320 | uM |
| (5E,8E,11E,14E,17E,20E)-N-[2,6-di(propan-2-yl)phenyl]docosa-5,8,11,14,17,20-hexaenamide | 30885: Compound was tested for inhibitory activity against ACAT from U937 microsome in human | ic50 | 0.0350 | uM |
| 1-[2,6-di(propan-2-yl)phenyl]-3-[[4-(3-methoxyphenyl)-1-phenylpiperidin-4-yl]methyl]urea | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0350 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0370 | uM |
| (3R,6S,9S,13S)-9-benzhydryl-3-[(2S)-butan-2-yl]-13-[(2S)-hexan-2-yl]-6-methyl-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | 638437: Inhibition of ACAT1- mediated cholesteryl ester synthesis in macrophages | ic50 | 0.0400 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[4-(3-methoxyphenyl)-1-phenylpiperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0400 | uM |
| 1-[5-[(4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]pentyl]-3,5-dimethylpyrazole | 1943488: Inhibition of ACAT in human THP-1 | ic50 | 0.0400 | uM |
| N-[(1S,2R)-2-(4-hydroxyphenyl)-2,3-dihydro-1H-inden-1-yl]-2,2-diphenylacetamide | 31522: Inhibition of Acyl coenzyme A:cholesterol acyltransferase (ACAT) | ic50 | 0.0400 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1,4-bis(2-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0430 | uM |
| 1-[2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl]urea | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0470 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1,4-bis(3-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0480 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[4-(3-methoxyphenyl)-1-[2-(2,2,2-trifluoroethoxy)phenyl]piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0480 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-(4-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0490 | uM |
| 2-[4-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]piperazin-1-yl]-1,3-thiazole | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0500 | uM |
| N-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-N-methylpyridin-2-amine | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0500 | uM |
| [(2S,5S,6R,9S,10S,18R)-5,9-diacetyloxy-18-hydroxy-2,6,10-trimethyl-16-oxo-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-6-yl]methyl acetate | 31814: Inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) | ic50 | 0.0580 | uM |
| 1-[5-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]pentyl]-3,5-dimethylpyrazole | 31532: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the activity of human Acyl coenzyme A:cholesterol acyltransferase 1 | ic50 | 0.0600 | uM |
| 2-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-3,4-dihydro-1H-isoquinoline | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0600 | uM |
| 1-[3-[2-(4,5-diphenyl-1H-imidazol-2-yl)-1,3-dioxan-5-yl]propyl]-3,5-dimethylpyrazole | 1943488: Inhibition of ACAT in human THP-1 | ic50 | 0.0600 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[4-(3-methoxyphenyl)-1-[2-(trifluoromethoxy)phenyl]piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0680 | uM |
| 4-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]thiomorpholine | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0700 | uM |
| 1-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-4-phenylpiperazine | 31532: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the activity of human Acyl coenzyme A:cholesterol acyltransferase 1 | ic50 | 0.0700 | uM |
| 4-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-1,3-dioxan-5-yl]butyl]thiomorpholine | 1943488: Inhibition of ACAT in human THP-1 | ic50 | 0.0700 | uM |
| 2-[4-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]piperazin-1-yl]pyrimidine | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.0750 | uM |
| 1-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-3,5-dimethylpyrazole | 31528: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme | ic50 | 0.0750 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[4-(3-fluorophenyl)-1-(2-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0770 | uM |
| ethyl 6-(3-benzyl-1,2,4-oxadiazol-5-yl)-2-morpholin-4-yl-4-phenyl-7-propylpyrrolo[1,2-b]pyridazine-5-carboxylate | 517640: Inhibition of human full-length flag-tagged ACAT1 expressed in baculovirus infected insect cells after 10 mins | ic50 | 0.0770 | uM |
| 1-[3-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-(3-methoxyphenyl)piperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0810 | uM |
| 1-[4-amino-2,6-di(propan-2-yl)phenyl]-3-[[1-(2-methoxyphenyl)-4-phenylpiperidin-4-yl]methyl]urea;dihydrochloride | 392882: Inhibition of ACAT in human HepG2 cells | ic50 | 0.0820 | uM |
| ethyl 6-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-2-morpholin-4-yl-4-phenyl-7-propylpyrrolo[1,2-b]pyridazine-5-carboxylate | 517640: Inhibition of human full-length flag-tagged ACAT1 expressed in baculovirus infected insect cells after 10 mins | ic50 | 0.0830 | uM |
| N-[2,6-di(propan-2-yl)phenyl]tetradecanethioamide | 30884: Compound was tested for inhibitory activity against ACAT from HepG2 microsome in human | ic50 | 0.0890 | uM |
| 1-benzyl-4-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]piperazine | 31532: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the activity of human Acyl coenzyme A:cholesterol acyltransferase 1 | ic50 | 0.0900 | uM |
| N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]-2-[4-[2-([1,3]oxazolo[4,5-b]pyridin-2-ylsulfanyl)ethyl]piperazin-1-yl]acetamide | 1419341: Inhibition of ACAT in human J774A.1 cells assessed as reduction in esterified-cholesterol accumulation after 18 hrs in presence of 25-hydroxycholesterol by cholesterol E-test analysis | ic50 | 0.1000 | uM |
| diethyl 2-morpholin-4-yl-4-phenyl-7-(4-phenylmethoxyphenyl)pyrrolo[1,2-b]pyridazine-5,6-dicarboxylate | 517640: Inhibition of human full-length flag-tagged ACAT1 expressed in baculovirus infected insect cells after 10 mins | ic50 | 0.1000 | uM |
| 1-[4-[2-(4,5-diphenyl-1H-imidazol-2-yl)-5-methyl-1,3-dioxan-5-yl]butyl]-4-pyridin-2-ylpiperazine | 31529: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the Acyl coenzyme A:cholesterol acyltransferase 1 activity obtained from human THP-1 macrophage enzyme. | ic50 | 0.1050 | uM |
| 2-[5-methyl-5-[4-(4-phenylpyrazol-1-yl)butyl]-1,3-dioxan-2-yl]-4,5-diphenyl-1H-imidazole | 31532: Inhibitory concentration was evaluated as concentration required to inhibit 50% of the activity of human Acyl coenzyme A:cholesterol acyltransferase 1 | ic50 | 0.1100 | uM |
| (3R,6S,9S,13S)-9-benzhydryl-3-[(2S)-butan-2-yl]-13-[(2S)-hexan-2-yl]-6-(hydroxymethyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | 638437: Inhibition of ACAT1- mediated cholesteryl ester synthesis in macrophages | ic50 | 0.1100 | uM |
| [(1S,2S,5S,6R,7R,9S,10S,18R)-5-acetyloxy-6-(acetyloxymethyl)-18-hydroxy-2,6,10-trimethyl-16-oxo-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-9-yl] 3-methylsulfanylbenzoate | 732690: Inhibition of ACAT1 (unknown origin) expressed in CHO cells | ic50 | 0.1100 | uM |
| (1R,2S,3R,11R,13S,16S,17S,19R,20R,22S,25S,27S)-9-[(3,3-dimethyloxiran-2-yl)methyl]-3-methoxy-1,2,24,24-tetramethyl-22-(2-methylprop-1-enyl)-18,21,23,26-tetraoxa-4-azaoctacyclo[14.13.0.02,13.03,11.05,10.017,19.017,27.020,25]nonacosa-5,7,9-triene-11,16-diol | 1940244: Inhibition of SOAT1 (unknown origin) | ic50 | 0.1200 | uM |
CTD chemical–gene interactions
48 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects cotreatment, increases expression, affects expression | 6 |
| Air Pollutants | decreases expression, affects cotreatment, increases abundance, increases oxidation | 3 |
| entinostat | increases expression, affects cotreatment | 2 |
| Phenylmercuric Acetate | affects cotreatment, decreases expression | 2 |
| Cyclosporine | decreases expression, increases methylation | 2 |
| Particulate Matter | decreases expression, increases abundance, increases expression | 2 |
| FR900359 | decreases phosphorylation | 1 |
| dicrotophos | decreases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| alpha-pinene | affects cotreatment, increases oxidation, increases abundance | 1 |
| sodium arsenate | increases abundance, increases expression | 1 |
| sodium arsenite | increases expression | 1 |
| methacrylaldehyde | affects cotreatment, increases oxidation, increases abundance | 1 |
| S-1,2-dichlorovinyl-N-acetylcysteine | affects expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, increases expression, decreases expression | 1 |
| gypenoside | decreases expression | 1 |
| ICG 001 | decreases expression | 1 |
| abrine | decreases expression | 1 |
| dorsomorphin | affects cotreatment, increases expression, decreases expression | 1 |
| Vorinostat | increases expression | 1 |
| Acetaminophen | increases expression | 1 |
| Acrolein | affects cotreatment, increases oxidation, increases abundance | 1 |
| Air Pollutants, Occupational | decreases expression | 1 |
| Arsenic | increases abundance, increases expression | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Biological Factors | decreases expression | 1 |
| Cadmium | increases abundance, increases expression | 1 |
| Cisplatin | increases expression | 1 |
| Cyclophosphamide | affects response to substance | 1 |
| Fluorouracil | affects response to substance | 1 |
ChEMBL screening assays
136 unique, capped per target: 127 binding, 8 functional, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1022201 | Binding | Inhibition of human ACAT1 at 10 uM by liquid scintillography | Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor. — J Med Chem |
| CHEMBL4392492 | ADMET | Inhibition of human ACAT1 | Accelerating the discovery of DGAT1 inhibitors through the application of parallel medicinal chemistry (PMC). — Bioorg Med Chem Lett |
| CHEMBL638497 | Functional | Effect on Cholesterol O-Acyltransferase (ACAT)-catalyzed cholesteryl oleate formation (COF) in cultured monkey arterial smooth muscle cells in experiment 2 in the presence ofCationized Low-density lipoproteins +3 uM | Potential antiatherosclerotic agents. 5. An acyl-CoA:cholesterol O-acyltransferase inhibitor with hypocholesterolemic activity. — J Med Chem |
Cellosaurus cell lines
5 cell lines: 5 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B2H0 | Abcam HeLa SOAT1 KO | Cancer cell line | Female |
| CVCL_E1K4 | HyCyte HCT 116 KO-hSOAT1 | Cancer cell line | Male |
| CVCL_TP94 | HAP1 SOAT1 (-) 1 | Cancer cell line | Male |
| CVCL_TP95 | HAP1 SOAT1 (-) 2 | Cancer cell line | Male |
| CVCL_TP96 | HAP1 SOAT1 (-) 3 | Cancer cell line | Male |
Clinical trials (associated diseases)
111 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT01052623 | PHASE4 | UNKNOWN | Status of Growth Hormone/ Insulin-like Growth Factor-1 (GH/IGF-1) Axis and Growth Failure in Ataxia Telangiectasia (AT) |
| NCT02733679 | PHASE4 | COMPLETED | Response of Individuals With Ataxia-Telangiectasia to Metformin and Pioglitazone |
| NCT00417066 | PHASE4 | COMPLETED | Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders |
| NCT00732693 | PHASE4 | COMPLETED | Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure |
| NCT00837616 | PHASE4 | COMPLETED | Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism |
| NCT01853501 | PHASE4 | UNKNOWN | Effects of ADSC Therapy in Women With POF |
| NCT02783937 | PHASE4 | COMPLETED | Filgrastim for Premature Ovarian Insufficiency |
| NCT03535480 | PHASE4 | UNKNOWN | Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure |
| NCT00656409 | PHASE3 | COMPLETED | Conjugate Pneumococcal Vaccine in Ataxia Telangiectasia (AT) |
| NCT03563053 | PHASE3 | TERMINATED | Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study |
| NCT06193200 | PHASE3 | COMPLETED | Evaluate the Neurological Effects of EryDex on Subjects With A-T |
| NCT06664853 | PHASE3 | TERMINATED | Open-Label Extension of EryDex Study IEDAT-04-2022 |
| NCT06673056 | PHASE3 | ACTIVE_NOT_RECRUITING | A Pivotal Study of N-Acetyl-L-Leucine on Ataxia-Telangiectasia (A-T) |
| NCT00140998 | PHASE3 | COMPLETED | Estrogen Treatment (Oral vs. Patches) in Turner Syndrome |
| NCT03759678 | PHASE2 | TERMINATED | N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T) |
| NCT03962114 | PHASE2 | COMPLETED | Effects of Vitamin B3 in Patients With Ataxia Telangiectasia |
| NCT04513002 | PHASE2 | COMPLETED | Ataxia-telangiectasia: Treating Mitochondrial Dysfunction With a Novel Form of Anaplerosis |
| NCT04870866 | PHASE2 | ACTIVE_NOT_RECRUITING | NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia |
| NCT04887311 | PHASE2 | UNKNOWN | MBM-01 (Tempol) for the Treatment of Ataxia Telangiectasia |
| NCT00001951 | PHASE2 | COMPLETED | Hormone Replacement in Young Women With Premature Ovarian Failure |
| NCT00370019 | PHASE2 | WITHDRAWN | Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure |
| NCT00429494 | PHASE2 | COMPLETED | GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients |
| NCT03816852 | PHASE2 | SUSPENDED | The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency |
| NCT04536467 | PHASE2 | UNKNOWN | Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients |
| NCT06117982 | PHASE2 | COMPLETED | The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency |
| NCT05531890 | PHASE1 | UNKNOWN | Comparative Bioavailability of Betamethasone Oral Solution Metered Spray (GTX-102) in Healthy Subjects |
| NCT02912104 | PHASE1 | COMPLETED | A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure |
| NCT03178695 | PHASE1 | COMPLETED | Inovium Ovarian Rejuvenation Trials |
| NCT04815213 | PHASE1 | ACTIVE_NOT_RECRUITING | The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans |
| NCT05138367 | PHASE1 | COMPLETED | Effects of UCA-PSCs in Women With POF |
| NCT06132542 | PHASE1 | UNKNOWN | Autologous ADMSC Transplantation in Patients With POI |
| NCT03655223 | Not specified | ENROLLING_BY_INVITATION | Early Check: Expanded Screening in Newborns |
| NCT05687474 | Not specified | COMPLETED | Baby Detect : Genomic Newborn Screening |
| NCT05910151 | Not specified | UNKNOWN | Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan |
| NCT07215416 | PHASE1/PHASE2 | RECRUITING | Safety and Efficacy of Mutation-targeted Precision Genetic Therapy for Ataxia-Telangiectasia (A-T) |
| NCT00640003 | EARLY_PHASE1 | COMPLETED | Baclofen Treatment of Ataxia Telangiectasia |
| NCT00187057 | Not specified | COMPLETED | Study for Treatment of Cancer in Children With Ataxia-telangiectasia |
| NCT00951886 | Not specified | UNKNOWN | The Validity of Forced Expiratory Maneuvers in Ataxia Telangiectasia Studied Longitudinally |
| NCT01075438 | Not specified | UNKNOWN | Immunogenicity of Pneumococcal Vaccines in Ataxia-telangiectasia Patients |
| NCT01793168 | Not specified | RECRUITING | Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford |
Related Atlas pages
- Associated diseases: beta-ketothiolase deficiency
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): ataxia telangiectasia, beta-ketothiolase deficiency, primary ovarian failure