SOAT2

gene
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Also known as ACAT2

Summary

SOAT2 (sterol O-acyltransferase 2, HGNC:11178) is a protein-coding gene on chromosome 12q13.13, encoding Sterol O-acyltransferase 2 (O75908). Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol.

Summary:This gene is a member of a small family of acyl coenzyme A:cholesterol acyltransferases. The gene encodes a membrane-bound enzyme localized in the endoplasmic reticulum that produces intracellular cholesterol esters from long-chain fatty acyl CoA and cholesterol. The cholesterol esters are then stored as cytoplasmic lipid droplets inside the cell. The enzyme is implicated in cholesterol absorption in the intestine and in the assembly and secretion of apolipoprotein B-containing lipoproteins such as very low density lipoprotein (VLDL). Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 8435 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 94 total
  • Druggable target: yes — 4 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_003578

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11178
Approved symbolSOAT2
Namesterol O-acyltransferase 2
Location12q13.13
Locus typegene with protein product
StatusApproved
AliasesACAT2
Ensembl geneENSG00000167780
Ensembl biotypeprotein_coding
OMIM601311
Entrez8435

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000301466, ENST00000542365, ENST00000551896, ENST00000869109, ENST00000869110, ENST00000869111, ENST00000869112, ENST00000869113, ENST00000869114, ENST00000869115

RefSeq mRNA: 1 — MANE Select: NM_003578 NM_003578

CCDS: CCDS8847

Canonical transcript exons

ENST00000301466 — 15 exons

ExonStartEnd
ENSE000011169285310556153105620
ENSE000011169365311835053118434
ENSE000011169385310510753105243
ENSE000011169415310590753106014
ENSE000011169425311539053115654
ENSE000011169445310415153104206
ENSE000011169465311609753116166
ENSE000011169515311889053118935
ENSE000015920335312407353124535
ENSE000034683815312308153123216
ENSE000034716685312372853123873
ENSE000036060785311912453119253
ENSE000036392335312130353121401
ENSE000036580525312078653120883
ENSE000038485765310348653103659

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 88.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4956 / max 100.3321, expressed in 100 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
1257080.423082
1257060.038321
1257070.034321

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
jejunal mucosaUBERON:000039988.13gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047387.51gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099184.21gold quality
duodenumUBERON:000211480.36gold quality
spleenUBERON:000210674.32gold quality
right lobe of liverUBERON:000111470.62gold quality
small intestineUBERON:000210869.21gold quality
small intestine Peyer’s patchUBERON:000345468.31gold quality
jejunumUBERON:000211566.78gold quality
ileal mucosaUBERON:000033165.45silver quality
mucosa of stomachUBERON:000119964.33gold quality
tibial nerveUBERON:000132363.49gold quality
liverUBERON:000210763.40gold quality
thoracic aortaUBERON:000151562.96gold quality
ascending aortaUBERON:000149662.85gold quality
descending thoracic aortaUBERON:000234562.53gold quality
aortaUBERON:000094762.42gold quality
popliteal arteryUBERON:000225062.14gold quality
tibial arteryUBERON:000761062.08gold quality
trabecular bone tissueUBERON:000248361.48gold quality
granulocyteCL:000009460.26gold quality
endocervixUBERON:000045860.24gold quality
deciduaUBERON:000245059.05gold quality
left coronary arteryUBERON:000162658.82gold quality
secondary oocyteCL:000065558.15gold quality
right coronary arteryUBERON:000162557.97gold quality
coronary arteryUBERON:000162157.74gold quality
gingival epitheliumUBERON:000194957.24gold quality
left uterine tubeUBERON:000130356.67gold quality
skin of legUBERON:000151156.47gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no1.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1B, HNF4A

miRNA regulators (miRDB)

16 targeting SOAT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4533100.0069.482758
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-137-3P99.8774.742401
HSA-MIR-6857-5P99.8765.32985
HSA-MIR-4999-5P99.3569.15926
HSA-MIR-7160-5P99.1167.172207
HSA-MIR-6760-5P98.8766.731515
HSA-MIR-502-5P98.7766.51906
HSA-MIR-6894-5P98.7063.78809
HSA-MIR-4726-3P98.4963.891385
HSA-MIR-6780A-3P98.4267.491518
HSA-MIR-58198.3967.42835
HSA-MIR-316698.2466.631223
HSA-MIR-6511B-5P97.9865.64823
HSA-MIR-6811-5P97.9864.96848
HSA-MIR-426496.3564.761480

Literature-anchored findings (GeneRIF, showing 28)

  • We found a new single-nucleotide polymorphism (SNP; a point mutation in intron 1, IVS1 -8 G–>C) in the ACAT-2 gene. Our data suggest that the ACAT-2 gene may not affect lipid levels in humans. (PMID:12621162)
  • Fully differentiated macrophages express ACAT2 in addition to ACAT1 under various pathologic conditions. (PMID:14615411)
  • 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)
  • increasing DGAT1, ACAT1, or ACAT2 expression stimulates the assembly and secretion of VLDL from liver cells (PMID:15308631)
  • ACAT2 provided the major cholesterol-esterifying activity in 3 of 4 human liver samples. (PMID:15451793)
  • transcription factors hepatic nuclear factor 1 (HNF1)alpha and beta play an important part in the regulation of the ACAT2 promoter (PMID:15961790)
  • The structural features of various sterols as substrates and/or activators of ACAT1 and ACAT2 in vitro are reported. (PMID:15992359)
  • 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)
  • Elevated ACAT2 expression may serve as a new biomarker for certain form(s) of hepatocellular carcinoma. (PMID:16274362)
  • Alternative splicing produces two human ACAT2 mRNA variants that encode the novel ACAT2 isoenzymes. Our findings might help to understand the regulation of the ACAT2 gene expression under certain physiological and pathological conditions. (PMID:16331323)
  • 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)
  • We resequenced 4 candidate genes for HDL regulation and identified several functional nonsynonymous mutations including 4 in lecithin:cholesterol acyltransferase (LCAT), leaving 88% (110/124) of HDL deficient subjects without a genetic diagnosis. (PMID:17303779)
  • human ACAT2 is transcriptionally regulated by cholesterol. (PMID:17950700)
  • ACAT2 expression was induced upon R1881 (androgen agonist) treatment in prostate cancer cells (PMID:18000807)
  • ACAT-2 expression was negative in clear cell type renal cell carcinoma and normal kidney. (PMID:18269457)
  • Describe a gender-related difference in hepatic ACAT2 activity in normolipidemic non-obese Chinese patients suggesting a possible role for ACAT2 in the regulation of cholesterol metabolism in humans. (PMID:19467657)
  • HNF4alpha positively regulates ACAT2 gene expression at mRNA level. Overexpression of HNF4alpha increased ACAT2 expression, whereas knockdown of HNF4alpha decreased ACAT2 expression. (PMID:22155889)
  • CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. (PMID:24103759)
  • TG-interacting factor 1 (Tgif1) is an important repressor of SOAT2 gene expression. (PMID:24478032)
  • results show that the enzymatic activity of mutant Glu(14)Gly is approximately two times higher than wildtype, and that this increase is primarily due to the increased expression and/or stability of the mutant ACAT2 protein (PMID:25917363)
  • Low ACAT2 expression is associated with clear cell renal cell carcinoma. (PMID:26715271)
  • data demonstrate that the ACAT2 expression of human leukocytes is responsible for the excretion of lipoproteins containing cholesteryl/steryl esters (CE/SE), and suggest that the excretion of lipoproteins containing the ACAT2-catalyzed CS/SE may avoid cytotoxicity (PMID:27688150)
  • Lipid-induced stabilization of ACAT2 ameliorates lipotoxicity from excessive cholesterol and fatty acid. Cysteine ubiquitylation of ACAT2 constitutes an important mechanism for sensing lipid-overload-induced ROS and fine-tuning lipid homeostasis. (PMID:28604676)
  • Single nucleotide polymorphisms Rs28765985 of ACAT-2 (SOAT2) gene are associated with increased susceptibility to coronary artery disease in Uygur population in Xinjiang, China. (PMID:30696703)
  • Whole-exome sequencing and genome-wide association studies identify novel sarcopenia risk genes in Han Chinese. (PMID:32478482)
  • Sterol O-acyltransferase 2 chaperoned by apolipoprotein J facilitates hepatic lipid accumulation following viral and nutrient stresses. (PMID:33980978)
  • Identification of the prognostic value of Th1/Th2 ratio and a novel prognostic signature in basal-like breast cancer. (PMID:36694223)
  • ACAT2 may be a novel predictive biomarker and therapeutic target in lung adenocarcinoma. (PMID:38213102)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriosoat2ENSDARG00000059824
mus_musculusSoat2ENSMUSG00000023045
rattus_norvegicusSoat2ENSRNOG00000053769
drosophila_melanogasterCG8112FBGN0037612
caenorhabditis_elegansWBGENE00007174

Paralogs (2): SOAT1 (ENSG00000057252), DGAT1 (ENSG00000185000)

Protein

Protein identifiers

Sterol O-acyltransferase 2O75908 (reviewed: O75908)

Alternative names: Acyl-coenzyme A:cholesterol acyltransferase 2, Cholesterol acyltransferase 2

All UniProt accessions (2): O75908, F8VPE9

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. Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa. Has lower enzymatic activity compared to isoform 1. Has lower enzymatic activity compared to isoform 1.

Subunit / interactions. May form homo- or heterodimers. Interacts with INSIG1; the interaction is direct and promotes association with AMFR/gp78.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expression seems confined in hepatocytes and enterocytes.

Post-translational modifications. Polyubiquitinated by AMFR/gp78 at Cys-277, leading to its degradation when the lipid levels are low. Association with AMFR/gp78 is mediated via interaction with INSIG1. High concentration of cholesterol and fatty acid results in Cys-277 oxidation, preventing ubiquitination at the same site, resulting in protein stabilization. Oxidized at Cys-277: high concentration of cholesterol and fatty acid induce reactive oxygen species, which oxidizes Cys-277, preventing ubiquitination at the same site, and resulting in protein stabilization.

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.

Similarity. Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.

Isoforms (4)

UniProt IDNamesCanonical?
O75908-11, ACAD2ayes
O75908-22, ACAD2b
O75908-33, ACAD2c
O75908-44

RefSeq proteins (1): NP_003569* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004299MBOAT_famFamily
IPR014371Oat_ACAT_DAG_AREFamily
IPR030687Sterol_acyltranf_metaFamily

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.

SubstrateKm (mM)Measurements
OLEOYL-COA0.0013–0.06912
CIS-9-OCTADECENOYL-COA6
CHOLESTEROL0.0016–0.062
ELAIDOYL-COA0.00221
LINOLEOYL-COA0.00281
PALMITOYL-COA0.0381
PREGNENOLONE0.00121
STEAROYL-COA0.00641

Catalyzed reactions (Rhea), 6 shown:

  • an acyl-CoA + cholesterol = a cholesterol ester + CoA (RHEA:17729)
  • cholesterol + (9Z)-octadecenoyl-CoA = cholesteryl (9Z-octadecenoate) + CoA (RHEA:41436)
  • (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + cholesterol = cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA (RHEA:42816)
  • (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + cholesterol = (5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-cholesterol + CoA (RHEA:46612)
  • (9Z,12Z,15Z)-octadecatrienoyl-CoA + cholesterol = (9Z,12Z,15Z-octadecatrienoyl)-cholesterol + CoA (RHEA:46620)
  • a sterol + a long-chain fatty acyl-CoA = a long-chain 3-hydroxysterol ester + CoA (RHEA:59816)

UniProt features (55 total): mutagenesis site 13, topological domain 10, transmembrane region 9, binding site 7, splice variant 5, region of interest 2, sequence variant 2, chain 1, short sequence motif 1, compositionally biased region 1, active site 1, modified residue 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDBMethodResolution (Å)
7N6QELECTRON MICROSCOPY3.87
7N6RELECTRON MICROSCOPY3.93

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O75908-F182.590.49

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): 434

Ligand- & substrate-binding residues (7): 119; 389; 392; 395; 399; 407; 430

Post-translational modifications (2): 277, 277

Mutagenesis-validated functional residues (13):

PositionPhenotype
49in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-80, r-100, r
80in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-100, r
100in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-80, r-
102in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-80, r-
108in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-80, r-
242in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-80, r-
254does not affect ubiquitination and sterol-regulated stabilization; when associated with r-279.
267–270does not affect ubiquitination and sterol-regulated stabilization.
277abolished ubiquitination and sterol-regulated stabilization.
279does not affect ubiquitination and sterol-regulated stabilization; when associated with r-54.
299in k-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with r-49, r-80, r-
360abolished cholesterol o-acyltransferase activity.
399abolished cholesterol o-acyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-8964038LDL clearance
R-HSA-174824Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551Transport of small molecules
R-HSA-8964043Plasma lipoprotein clearance

MSigDB gene sets: 419 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_DIGESTION, HORIUCHI_WTAP_TARGETS_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_STEROL_HOMEOSTASIS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, YANG_BREAST_CANCER_ESR1_LASER_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS, GOBP_PROTEIN_LIPID_COMPLEX_ASSEMBLY, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MORF_RAD51L3, GOBP_LOW_DENSITY_LIPOPROTEIN_PARTICLE_CLEARANCE

GO Biological Process (11): cholesterol metabolic process (GO:0008203), macrophage derived foam cell differentiation (GO:0010742), cholesterol storage (GO:0010878), intestinal cholesterol absorption (GO:0030299), 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 intestinal cholesterol absorption (GO:0045797), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)

GO Molecular Function (8): fatty-acyl-CoA binding (GO:0000062), sterol O-acyltransferase activity (GO:0004772), cholesterol binding (GO:0015485), acyltransferase activity (GO:0016746), cholesterol O-acyltransferase activity (GO:0034736), protein binding (GO:0005515), obsolete O-acyltransferase activity (GO:0008374), transferase activity (GO:0016740)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), brush border (GO:0005903), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Plasma lipoprotein clearance1
Transport of small molecules1
Plasma lipoprotein assembly, remodeling, and clearance1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
sterol metabolic process1
secondary alcohol metabolic process1
foam cell differentiation1
lipid storage1
lipid digestion1
intestinal lipid absorption1
cholesterol transport1
plasma lipoprotein particle assembly1
plasma lipoprotein particle clearance1
low-density lipoprotein particle disassembly1
sterol homeostasis1
intestinal cholesterol absorption1
regulation of intestinal cholesterol absorption1
positive regulation of intestinal lipid absorption1
primary metabolic process1
lipid metabolic process1
acyl-CoA binding1
fatty acid derivative binding1
acyltransferase activity, transferring groups other than amino-acyl groups1
sterol binding1
alcohol binding1
transferase activity1
sterol O-acyltransferase activity1
binding1
catalytic activity1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
microvillus1
apical part of cell1
cluster of actin-based cell projections1
cellular anatomical structure1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SOAT2VPS52Q8N1B4856
SOAT2IGFBP6P24592837
SOAT2KRT2P35908736
SOAT2APOBP04114707
SOAT2DGAT2Q96PD7705
SOAT2HMGCRP04035664
SOAT2NPC1L1Q9UHC9628
SOAT2RARGP13631615
SOAT2LCATP04180608
SOAT2ABCG5Q9H222599
SOAT2ITGB7P26010554
SOAT2ABCG8Q9H221547
SOAT2SREBF2Q12772519
SOAT2APOEP02649517
SOAT2MTTPP55157509

IntAct

10 interactions, top by confidence:

ABTypeScore
SOAT2TMBIM6psi-mi:“MI:0915”(physical association)0.560
SOAT2AKT1psi-mi:“MI:0915”(physical association)0.370
KSR1FBLL1psi-mi:“MI:0914”(association)0.350
RBM15ILVBLpsi-mi:“MI:2364”(proximity)0.270
SF3B4MED19psi-mi:“MI:2364”(proximity)0.270
YWHAGRPSA2psi-mi:“MI:2364”(proximity)0.270
DDX6RPSA2psi-mi:“MI:2364”(proximity)0.270
TMBIM6SOAT2psi-mi:“MI:0915”(physical association)0.000

BioGRID (8): AMFR (Affinity Capture-MS), AMFR (Affinity Capture-Western), INSIG1 (Affinity Capture-Western), SOAT2 (Synthetic Lethality), SOAT2 (Two-hybrid), SOAT2 (Affinity Capture-Western), SOAT2 (Affinity Capture-MS), SOAT2 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance77
Likely benign10
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3306 predictions. Top by Δscore:

VariantEffectΔscore
12:53105106:GGCT:Gacceptor_gain1.0000
12:53105240:GCAG:Gdonor_gain1.0000
12:53105242:AGG:Adonor_loss1.0000
12:53105244:GT:Gdonor_loss1.0000
12:53105245:T:Adonor_loss1.0000
12:53105621:G:GGdonor_gain1.0000
12:53105901:CTCTA:Cacceptor_loss1.0000
12:53105903:CTAGT:Cacceptor_loss1.0000
12:53105904:TAGT:Tacceptor_loss1.0000
12:53105904:TAGTG:Tacceptor_gain1.0000
12:53105905:A:AGacceptor_gain1.0000
12:53105905:AGT:Aacceptor_gain1.0000
12:53105905:AGTGA:Aacceptor_gain1.0000
12:53105906:G:GGacceptor_gain1.0000
12:53105906:GT:Gacceptor_gain1.0000
12:53105906:GTG:Gacceptor_gain1.0000
12:53105906:GTGA:Gacceptor_gain1.0000
12:53105906:GTGAG:Gacceptor_gain1.0000
12:53106010:GGCAG:Gdonor_gain1.0000
12:53106011:GCAG:Gdonor_gain1.0000
12:53106011:GCAGG:Gdonor_gain1.0000
12:53106012:C:Tdonor_gain1.0000
12:53106014:GGTA:Gdonor_loss1.0000
12:53106015:GT:Gdonor_loss1.0000
12:53106016:T:Gdonor_loss1.0000
12:53118346:CCA:Cacceptor_loss1.0000
12:53118349:GGT:Gacceptor_gain1.0000
12:53118349:GGTGA:Gacceptor_gain1.0000
12:53118433:AGGTA:Adonor_loss1.0000
12:53118436:T:Adonor_loss1.0000

AlphaMissense

3372 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:53121309:T:AW382R0.999
12:53121309:T:CW382R0.999
12:53121311:G:CW382C0.998
12:53121311:G:TW382C0.998
12:53121306:T:AW381R0.997
12:53121306:T:CW381R0.997
12:53121350:C:AN395K0.997
12:53121350:C:GN395K0.997
12:53120875:T:CF377L0.996
12:53120877:C:AF377L0.996
12:53120877:C:GF377L0.996
12:53120860:T:CF372L0.995
12:53120862:T:AF372L0.995
12:53120862:T:GF372L0.995
12:53120876:T:CF377S0.995
12:53121345:T:AW394R0.995
12:53121345:T:CW394R0.995
12:53123787:T:AW478R0.994
12:53123787:T:CW478R0.994
12:53118391:T:CF274L0.993
12:53118393:C:AF274L0.993
12:53118393:C:GF274L0.993
12:53120876:T:GF377C0.992
12:53121310:G:CW382S0.992
12:53121340:G:CR392P0.992
12:53123823:A:CS490R0.992
12:53123825:C:AS490R0.992
12:53123825:C:GS490R0.992
12:53105595:T:CF104L0.991
12:53105597:C:AF104L0.991

dbSNP variants (sampled 300 via entrez): RS1000013201 (12:53115078 A>G), RS1000209086 (12:53125019 G>A), RS1000830729 (12:53122853 C>T), RS1000836743 (12:53108182 T>A), RS1000893867 (12:53108560 T>C), RS1000948582 (12:53102506 C>T), RS1001117517 (12:53122659 A>C), RS1001216616 (12:53123412 T>A), RS1001229015 (12:53117458 A>G), RS1001301610 (12:53122247 C>A,T), RS1001400859 (12:53102897 C>T), RS1001456807 (12:53111367 A>C,G), RS1001522283 (12:53111358 C>T), RS1001573169 (12:53111720 C>A,G,T), RS1001635585 (12:53104821 G>A)

Disease associations

OMIM: gene MIM:601311 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST009144_5Disease progression in age-related macular degeneration (adjusted for baseline)7.000000e-06
GCST90000025_968Appendicular lean mass1.000000e-16

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0008336disease progression measurement
EFO:0004980appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4465 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 10,763 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL101309AVASIMIBE210,153
CHEMBL1908306EFLUCIMIBE2272
CHEMBL46423NEVANIMIBE278
CHEMBL478858PACTIMIBE2260

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

Binding affinities (BindingDB)

24 measured of 24 human assays (24 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
[4-[2-benzyl-5-[2,6-di(propan-2-yl)anilino]-3,5-dioxopentyl]phenyl] 2-(2-oxoazepan-1-yl)acetateIC503.2 nMUS-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)heptanoateIC503.6 nMUS-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-phenylpentanamideIC504.2 nMUS-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-oxopentanamideIC5010.3 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
(2S)-2-dodecylsulfanyl-N-(4-hydroxy-2,3,5-trimethylphenyl)-2-phenylacetamideIC5039 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
[(2R)-2-[(5aR,6R,8R,9aR,10S)-6,10-dihydroxy-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-8-yl]-2-hydroxypropyl] acetateIC5069 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
[(2R)-2-[(5aR,6R,8R,9aR,10R)-6,10-dihydroxy-5a-methyl-1-oxo-3-pyridin-3-yl-6,7,8,9,9a,10-hexahydropyrano[4,3-b]chromen-8-yl]-2-hydroxypropyl] acetateIC5081 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
(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 acetateIC50179 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
[2-[(5aS,6S,8S,9aS,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] acetateIC50245 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
[(2R)-2-[(5aR,6R,8R,9aR,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] acetateIC50433 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
2-[4-[2-(1H-benzimidazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-N-[6-methyl-2,4-bis(methylsulfanyl)-3-pyridinyl]acetamideIC50450 nMUS-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-tetroneIC50600 nMUS-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-tetroneIC50900 nMUS-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-cyanobenzoateIC5017800 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
1-[(1,3-diphenylpyrazol-5-yl)amino]decan-2-oneIC5023000 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
1-[(1,3-diphenylpyrazol-5-yl)amino]nonan-2-oneIC5024000 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
N-decyl-1,3-diphenylpyrazol-5-amineIC5039000 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
[(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] acetateIC5056700 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
N-(2-phenylphenyl)octanamideIC5061000 nMUS-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-cyanobenzoateIC5064700 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof
N-(2-phenylphenyl)nonanamideIC5065000 nMUS-9149492: Method for selectively inhibiting ACAT1 in the treatment of alzheimer’s disease
[(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] acetateIC5087400 nMUS-10278962: Tricyclic analogues, preparation method and uses 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] acetateIC50108000 nMUS-10278962: Tricyclic analogues, preparation method and uses 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-cyanobenzoateIC50154000 nMUS-10278962: Tricyclic analogues, preparation method and uses thereof

ChEMBL bioactivities

193 potent at pChembl≥5 of 227 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.10IC500.8nMCHEMBL2334538
9.05IC500.9nMCHEMBL2334540
9.05IC500.9nMCHEMBL2334539
9.05IC500.9nMCHEMBL2334222
9.00IC501nMCHEMBL2333808
9.00IC501nMCHEMBL2334541
8.92IC501.2nMCHEMBL2333809
8.77IC501.7nMCHEMBL2333810
8.70IC502nMCHEMBL2333811
8.57IC502.7nMCHEMBL2333812
8.40IC504nMCHEMBL2333813
8.30IC505nMCHEMBL2334212
8.30IC505nMCHEMBL2334199
8.30IC505nMCHEMBL2334198
8.30IC505nMCHEMBL2334197
8.30IC505nMCHEMBL2334196
8.30IC505nMCHEMBL2334195
8.30IC505nMCHEMBL2334194
8.25IC505.6nMCHEMBL2375701
8.22IC506nMCHEMBL2334213
8.22IC506nMCHEMBL2398815
8.21IC506.1nMCHEMBL2334214
8.20IC506.3nMCHEMBL2334215
8.19IC506.5nMCHEMBL2375702
8.18IC506.6nMCHEMBL2398812
8.17IC506.8nMCHEMBL2398811
8.15IC507nMCHEMBL2334216
8.15IC507nMCHEMBL2334200
8.15IC507nMCHEMBL2398816
8.14IC507.2nMCHEMBL2398813
8.11IC507.8nMCHEMBL2334217
8.11IC507.8nMCHEMBL2398806
8.09IC508.1nMCHEMBL2334218
8.05IC509nMCHEMBL2334201
8.05IC509nMCHEMBL2398817
8.02IC509.5nMCHEMBL2334221
8.02IC509.6nMCHEMBL2375707
8.01IC509.7nMCHEMBL2398808
8.00IC5010nMCHEMBL2334203
8.00IC5010nMCHEMBL2334202
8.00IC5010nMCHEMBL2334220
8.00IC5010nMCHEMBL2375705
8.00IC5010nMCHEMBL2398796
8.00IC5010nMCHEMBL2398818
7.96IC5011nMCHEMBL2334204
7.94IC5011.5nMCHEMBL2398804
7.93IC5011.8nMCHEMBL2398804
7.92IC5012nMCHEMBL4553029
7.89IC5013nMCHEMBL2398819
7.85IC5014nMCHEMBL2396678

PubChem BioAssay actives

151 with measured affinity, of 244 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.

CompoundAssayTypeValueUnit
[(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] 4-methoxybenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0008uM
[(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] 4-methylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0009uM
[(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] 4-cyanobenzoate1940249: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrsic500.0009uM
[(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-fluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0009uM
[(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] 4-chlorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0010uM
[(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] 4-ethylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0010uM
[(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-bromobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0012uM
[(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] 4-fluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0017uM
[(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] 4-bromobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0020uM
[(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] 4-methylsulfanylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0027uM
[(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] 4-iodobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0040uM
[(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] 4-azidobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(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] 4-bromo-3-fluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(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] 4-nitrobenzoate1940249: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrsic500.0050uM
[(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] 4-ethenylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(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-methylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(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-iodobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(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] 2-iodobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0050uM
[(1S,2S,5S,6R,7R,9S,10S,18R)-18-hydroxy-2,6,10-trimethyl-16-oxo-5-propanoyloxy-6-(propanoyloxymethyl)-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-9-yl] 4-cyanobenzoate744809: Inhibition of ACAT2 (unknown origin)ic500.0056uM
[(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-fluoro-4-nitrobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0060uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0060uM
[(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-fluoro-4-methoxybenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0061uM
[(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-fluoro-4-methylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0063uM
[(1S,2S,5S,6R,7R,9S,10S,18R)-18-hydroxy-2,6,10-trimethyl-5-(2-methylpropanoyloxy)-6-(2-methylpropanoyloxymethyl)-16-oxo-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-9-yl] 4-cyanobenzoate744809: Inhibition of ACAT2 (unknown origin)ic500.0065uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-18-(2,4-dimethylphenyl)-3-hydroxy-1,11,15-trimethyl-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0066uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-18-(2-fluorophenyl)-3-hydroxy-1,11,15-trimethyl-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0068uM
[(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] 4-bromo-2-fluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0070uM
[(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-chlorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0070uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-fluorobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0070uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-18-(2,6-dimethylphenyl)-3-hydroxy-1,11,15-trimethyl-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate1940249: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrsic500.0072uM
[(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] 4-cyano-3-fluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0078uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-18-(3-methylphenyl)-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0078uM
[(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] 2,3,4-trifluorobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0081uM
[(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-methylsulfanylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0090uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-chlorobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0090uM
[(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] 4-phenylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0095uM
[(1S,2S,5S,6R,7R,9S,10S,18R)-6-(acetyloxymethyl)-5-benzoyloxy-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] 4-cyanobenzoate744809: Inhibition of ACAT2 (unknown origin)ic500.0096uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-18-(4-methylphenyl)-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0097uM
[(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] benzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0100uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-18-(2-methylphenyl)-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] pentanoate1940249: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrsic500.0100uM
[(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-cyanobenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0100uM
[(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] 2-methylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0100uM
[(1S,2S,5S,6R,7R,9S,10S,18R)-6-(acetyloxymethyl)-18-hydroxy-2,6,10-trimethyl-16-oxo-5-propanoyloxy-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-9-yl] 4-cyanobenzoate744809: Inhibition of ACAT2 (unknown origin)ic500.0100uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-bromobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0100uM
[(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-ethenylbenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0110uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-18-(2-methylphenyl)-5-oxo-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-cyanobenzoate1940249: Inhibition of SOAT2 (unknown origin) expressed in CHO cells using [14C]oleic acid incubated for 6 hrsic500.0115uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 3-fluorobenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0130uM
[(1S,2S,3R,11S,12S,14R,15R,18R,20S)-3-hydroxy-1,11,15-trimethyl-5-oxo-18-phenyl-7-pyridin-3-yl-6,10,17,19-tetraoxapentacyclo[12.8.0.02,11.04,9.015,20]docosa-4(9),7-dien-12-yl] 4-methoxybenzoate755668: Inhibition of ACAT2 (unknown origin)ic500.0140uM
[(1S,2S,5S,6R,7R,9S,10S,18R)-5-acetyloxy-18-hydroxy-2,6,10-trimethyl-16-oxo-6-(propanoyloxymethyl)-14-pyridin-3-yl-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-12(17),13-dien-9-yl] 4-cyanobenzoate744809: Inhibition of ACAT2 (unknown origin)ic500.0144uM
[(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-methoxybenzoate732688: Inhibition of ACAT2 (unknown origin) expressed in CHO cellsic500.0150uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyrenedecreases expression, increases methylation3
Tetrachlorodibenzodioxindecreases expression2
aristolochic acid Iincreases expression1
bisphenol Aaffects expression1
kojic acidincreases expression1
beta-lapachonedecreases expression1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanonedecreases expression1
mono-(2-ethylhexyl)phthalatedecreases expression1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
butyraldehydeincreases expression1
periodate-oxidized adenosineaffects expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression1
CGP 52608affects binding, increases reaction1
Dustdecreases expression1
Hydrogen Peroxideaffects expression1
Lipopolysaccharidesaffects response to substance, increases expression1
Quercetindecreases expression1
Silicon Dioxideincreases expression1
Urethanedecreases expression1
Valproic Acidaffects expression1
Cyclosporinedecreases expression1
Aflatoxin B1affects methylation1
Copper Sulfatedecreases expression1
Vitamin K 3affects expression1

ChEMBL screening assays

50 unique, capped per target: 50 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1272846BindingInhibition of human ACAT2 expressed in CHO cells assessed as inhibition of [3H]oleate-induced cholesterol ester accumulationThe tomato saponin, esculeoside A. — J Nat Prod

Clinical trials (associated diseases)

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

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