ACLY

Summary

ACLY (ATP citrate lyase, HGNC:115) is a protein-coding gene on chromosome 17q21.2, encoding ATP-citrate synthase (P53396). Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism. It is a selective cancer dependency (DepMap: 47.4% of cell lines).

ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Multiple transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 47 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 169 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 47.4% of screened cell lines
• MANE Select transcript: NM_001096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:115
Approved symbol	ACLY
Name	ATP citrate lyase
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	ATPCL, CLATP, ACL
Ensembl gene	ENSG00000131473
Ensembl biotype	protein_coding
OMIM	108728
Entrez	47

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 50 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000352035, ENST00000353196, ENST00000393896, ENST00000537919, ENST00000588547, ENST00000588779, ENST00000590151, ENST00000590735, ENST00000590770, ENST00000592970, ENST00000884501, ENST00000884502, ENST00000884503, ENST00000884504, ENST00000884505, ENST00000884506, ENST00000884507, ENST00000884508, ENST00000884509, ENST00000884510, ENST00000884511, ENST00000884512, ENST00000884513, ENST00000884514, ENST00000884515, ENST00000884516, ENST00000937133, ENST00000937134, ENST00000937135, ENST00000937136, ENST00000937137, ENST00000937138, ENST00000937139, ENST00000937140, ENST00000937141, ENST00000937142, ENST00000937143, ENST00000937144, ENST00000937145, ENST00000937146, ENST00000937147, ENST00000937148, ENST00000937149, ENST00000937150, ENST00000941538, ENST00000941539, ENST00000941540, ENST00000941541, ENST00000941542, ENST00000941543, ENST00000941544, ENST00000941545, ENST00000941546

RefSeq mRNA: 4 — MANE Select: NM_001096 NM_001096, NM_001303274, NM_001303275, NM_198830

CCDS: CCDS11412, CCDS11413

Canonical transcript exons

ENST00000352035 — 29 exons

Exon	Start	End
ENSE00001936666	41866918	41867904
ENSE00002343399	41893033	41893174
ENSE00002355161	41913715	41913896
ENSE00002355247	41884193	41884274
ENSE00002358140	41887599	41887703
ENSE00002364662	41896620	41896649
ENSE00002366590	41872032	41872182
ENSE00002373858	41886112	41886308
ENSE00002377293	41883122	41883232
ENSE00002379846	41904729	41904790
ENSE00002382601	41912420	41912542
ENSE00002384010	41873811	41873965
ENSE00002386182	41892279	41892447
ENSE00002396459	41878103	41878196
ENSE00002400366	41878797	41878924
ENSE00002402004	41901696	41901813
ENSE00002418550	41897749	41897839
ENSE00002423081	41871689	41871832
ENSE00002424797	41906528	41906646
ENSE00002429109	41898631	41898785
ENSE00002853198	41918880	41918951
ENSE00003512002	41869043	41869125
ENSE00003515458	41869474	41869587
ENSE00003559977	41909510	41909700
ENSE00003600012	41907442	41907572
ENSE00003666333	41868709	41868785
ENSE00003671342	41905522	41905658
ENSE00003671814	41910222	41910284
ENSE00003675987	41908989	41909068

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.0891 / max 2058.4746, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166067	40.9685	1806
166068	25.6574	1816
166064	1.4093	783
166069	1.0539	634

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.80	gold quality
tibia	UBERON:0000979	98.54	gold quality
dorsal root ganglion	UBERON:0000044	98.45	gold quality
type B pancreatic cell	CL:0000169	98.20	gold quality
ganglionic eminence	UBERON:0004023	98.17	gold quality
stromal cell of endometrium	CL:0002255	97.99	gold quality
embryo	UBERON:0000922	97.96	gold quality
oocyte	CL:0000023	97.94	gold quality
pons	UBERON:0000988	97.86	gold quality
superior vestibular nucleus	UBERON:0007227	97.79	gold quality
nephron tubule	UBERON:0001231	97.78	gold quality
cortical plate	UBERON:0005343	97.71	gold quality
trigeminal ganglion	UBERON:0001675	97.51	gold quality
secondary oocyte	CL:0000655	97.48	gold quality
ventricular zone	UBERON:0003053	97.47	gold quality
choroid plexus epithelium	UBERON:0003911	97.31	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.29	gold quality
kidney epithelium	UBERON:0004819	97.12	gold quality
adrenal tissue	UBERON:0018303	97.12	gold quality
pericardium	UBERON:0002407	97.08	gold quality
cartilage tissue	UBERON:0002418	97.02	gold quality
medulla oblongata	UBERON:0001896	96.99	gold quality
ileal mucosa	UBERON:0000331	96.91	gold quality
jejunal mucosa	UBERON:0000399	96.85	gold quality
visceral pleura	UBERON:0002401	96.76	gold quality
renal glomerulus	UBERON:0000074	96.69	gold quality
synovial joint	UBERON:0002217	96.65	gold quality
metanephric glomerulus	UBERON:0004736	96.63	gold quality
pleura	UBERON:0000977	96.45	gold quality
inferior olivary complex	UBERON:0002127	96.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.43
E-GEOD-125970	no	3.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFYA, SP1, SP3, SREBF1, SREBF2

miRNA regulators (miRDB)

86 targeting ACLY, 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-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-1275	99.47	67.90	2749

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 47.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Constructed an Mre11(gp46) mutant protein with the conserved histidine changed to serine. The mutant protein was found to be completely defective for nuclease activities, but retained the ability to bind the Rad50(gp47) subunit and double-stranded DNA. (PMID:23979587)
• examine the kinetic and catalytic mechanism of ATP hydrolysis by Rad50 (gp46) in the presence and absence of Mre11 (gp47) and DNA (PMID:25137526)
• data presented indicate that the ATP citrate lyase pathway is operative in human platelets and may be responsible for increased acetyl-CoA in diabetic platelets which may be the cause of their excessive activity in the course of the disease (PMID:14681844)
• Atp citrate lyase is involved in lung cancer pathogenesis associated with metabolic abnormality and might offer a novel therapeutic target. (PMID:18922930)
• The activities of ATP citrate lyase were decreased by 57% in pancreatic islets of patients with type 2 diabetes. (PMID:19296078)
• findings suggest that ATP-citrate lyase activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression (PMID:19461003)
• ACLY is a positive regulator of glycolysis in glioblastoma cells. (PMID:19795461)
• Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography. (PMID:20558738)
• Data show that siRNA-mediated silencing of SREBP-1 and ATP citrate lyase significantly attenuated H(2)O(2)-induced senescence (PMID:20615871)
• Data suggest that ATP-citrate lyase (ACLY) expression and activity can be suppressed by exogenous lipids and demonstrate a critical role for ACLY in pancreatic beta cell survival. (PMID:20693577)
• Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets. (PMID:21454710)
• three major enzymes of the pathway, FASN, ACC, and ACLY, are up-regulated in numerous tumor types. (PMID:21726077)
• crystals of ATP-citrate lyase diffracted to 2.3 A resolution (PMID:22102020)
• Suggest that ATP citrate lyase may contribute to the pathogenesis of human epithelial ovarian cancer, and may serve as a novel therapeutic target. (PMID:22266777)
• Chemical modification, steady-state and pre-steady-state kinetics, and rapid kinetics collectively demonstrate the essential role of the active site His760 in the ACL reaction: His760 acts as a phosphate acceptor to initiate the biosynthetic reaction. (PMID:22657152)
• ACLY silencing clearly induces proliferation arrest and apoptosis in variety of cancer cell lines by affecting multiple downstream pathways. (PMID:22718913)
• The present review highlights current knowledge about the role of ACLY in cancer cells. (PMID:22787121)
• ATP citrate lyase is important for the pyruvate citrate shuttle and lipid synthesis in insulin secretion. (PMID:23225248)
• ACLY inhibition exerts an anticancer effect via increased reactive oxygen species, and p-AMPK could be a predictive biomarker for its therapeutic outcome. (PMID:23506848)
• ATP citrate lyase functions in cancer stem cells to regulate stemness. (PMID:23807225)
• Single nucleotide polymorphisms in the ACACA and ACLY genes are associated with a relative change in plasma triglycierides following fish oil supplementation. (PMID:23886516)
• ACLY mRNA and protein levels markedly and quickly increase in activated macrophages. Importantly, ACLY activity inhibition as well as ACLY gene silencing lead to reduced nitric oxide, reactive oxygen species and prostaglandin E2 inflammatory mediators. (PMID:24051091)
• ATP citrate lyase mediates resistance of colorectal cancer cells to SN38. (PMID:24132143)
• These data indicate that inhibition of ACLY might affect both fatty acid elongation in ER and FAO in mitochondria, thereby explaining the TG accumulation with altered fatty acid composition. (PMID:24310723)
• The activation of AMPK under ACLY knockdown conditions may lead to p53 activation, ultimately leading to cellular senescence. (PMID:25367309)
• SNP rs9912300 in ACLY gene was significantly associated with response to therapy in hepatocellular carcinoma (PMID:25735330)
• These results suggest that the combined expression of GLUT1 and ACLY could be a more valuable prognostic factor than their individual expression in node-negative patients with NSCLC. (PMID:25837797)
• Polymorphisms of ATP citrate lyase gene is associated with recurrence in colorectal cancer. (PMID:25890184)
• ACL activity is associated with increased ATP. Activation of this IGF1/ACL/cardiolipin pathway combines anabolic signaling with induction of mechanisms needed to provide required ATP. (PMID:26039450)
• ACC1 and ACLY regulate the levels of ETV4 under hypoxia via increased alpha-ketoglutarate. These results reveal that the ACC1/ACLY-alpha-ketoglutarate-ETV4 axis is a novel means by which metabolic states regulate transcriptional output (PMID:26452058)
• ACLY was also required for LMW-E-mediated transformation, migration, and invasion of breast cancer cells in vitro along with tumor growth in vivo In clinical specimens of breast cancer, the absence of LMW-E and low expression of adipophilin (PLIN2), a marker of lipid droplet formation, associated with favorable prognosis (PMID:26928812)
• Results show that ACLY is a key phosphoprotein effector of IL-2-mediated T-cell responses. ACLY becomes phosphorylated on serine 455 in T lymphocytes upon IL-2-driven activation of AKT, and depletion or inactivation of ACLY compromises IL-2-promoted T-cell growth. (PMID:27067055)
• CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells (PMID:27664236)
• ACLY and ACSS2 are both activated to produce cytosolic Ac-CoA from glucose carbon for lipogenesis during human cytomegalovirus infection. (PMID:28167750)
• we found that depletion of ATP citrate lyase suppressed tumor growth, which suggests that ATP citrate lyase-related inhibitors might be potential therapeutic approaches for breast cancer. (PMID:28443474)
• ACLY facilitates histone acetylation at double-strand break (DSB) sites, impairing 53BP1 localization and enabling BRCA1 recruitment and DNA repair by homologous recombination. ACLY phosphorylation and nuclear localization are necessary for its role in promoting BRCA1 recruitment. (PMID:28689661)
• The protein crystallized consisted of residues 2-425-ENLYFQ and S-488-810 of human ATP-citrate lyase. (2S,3S)-2-Hydroxycitrate binds in the same orientation as citrate, but the citrate-binding domain (residues 248-421) adopts a different orientation with respect to the rest of the protein (residues 4-247, 490-746 and 748-809) from that previously seen. (PMID:28777081)
• Results show that ACLY was up-regulated in human gastric cancer (GC) tissues and cell lines and a critical downstream target of the tumor suppressor activity of miR-133b in GC. (PMID:28901466)
• ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression. (PMID:29241530)
• Increased ACLY activity in osteoarthritis chondrocytes increased nucleocytosolic acetyl-CoA, leading to increased matrix catabolism via dysregulated histone and transcription factor acetylation. (PMID:29929979)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	aclyb	ENSDARG00000055652
danio_rerio	aclya	ENSDARG00000099079
mus_musculus	Acly	ENSMUSG00000020917
rattus_norvegicus	Acly	ENSRNOG00000016924
drosophila_melanogaster	ATPCL	FBGN0020236
caenorhabditis_elegans		WBGENE00007150
caenorhabditis_elegans		WBGENE00016995

Protein

Protein identifiers

ATP-citrate synthase — P53396 (reviewed: P53396)

Alternative names: ATP-citrate (pro-S-)-lyase, Citrate cleavage enzyme

All UniProt accessions (3): P53396, K7EIE7, K7ESG8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Post-translational modifications. Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity. Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455. Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues. Phosphorylated at Ser-455 by BCKDK and dephosphorylated by protein phosphatase PPM1K. ISGylated. Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF. Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites. Acetylation promotes de novo lipid synthesis. Deacetylated by SIRT2. Benzoylated at Lys-978. Debenzoylated by SIRT3; inhibiting the ATP-citrate synthase activity. Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site. BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells.

Activity regulation. Phosphorylation results in activation of its activity. Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators.

Similarity. In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family. In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
P53396-1	1	yes
P53396-2	2
P53396-3	3

RefSeq proteins (4): NP_001087, NP_001290203, NP_001290204, NP_942127 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002020	Citrate_synthase	Family
IPR003781	CoA-bd	Domain
IPR005811	SUCC_ACL_C	Domain
IPR014608	ATP-citrate_synthase	Family
IPR016102	Succinyl-CoA_synth-like	Homologous_superfamily
IPR016143	Citrate_synth-like_sm_a-sub	Homologous_superfamily
IPR017440	Cit_synth/succinyl-CoA_lig_AS	Active_site
IPR017866	Succ-CoA_synthase_bsu_CS	Conserved_site
IPR032263	Citrate-bd	Domain
IPR033847	Citrt_syn/SCS-alpha_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR036969	Citrate_synthase_sf	Homologous_superfamily
IPR056749	Citrate_synth_N	Domain

Pfam: PF00285, PF00549, PF02629, PF16114, PF24948

Enzyme classification (BRENDA):

• EC 2.3.3.8 — ATP citrate synthase (BRENDA: 55 organisms, 99 substrates, 152 inhibitors, 54 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.047–41	19
CITRATE	0.0308–6.25	17
COA	0.003–2.59	10
ACETYL-COA	0.0098	1
N6-ETHENO-ADENOSINE TRIPHOSPHATE	0.18	1
OXALOACETATE	0.177	1
PHOSPHATE	1.49	1

Catalyzed reactions (Rhea), 1 shown:

• oxaloacetate + acetyl-CoA + ADP + phosphate = citrate + ATP + CoA (RHEA:21160)

UniProt features (175 total): strand 55, helix 48, modified residue 20, binding site 16, sequence conflict 10, turn 9, mutagenesis site 5, cross-link 3, compositionally biased region 2, splice variant 2, chain 1, domain 1, region of interest 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6HXM	X-RAY DIFFRACTION	1.3
6HXL	X-RAY DIFFRACTION	1.35
5TDE	X-RAY DIFFRACTION	1.7
5TDF	X-RAY DIFFRACTION	1.8
6Z2H	X-RAY DIFFRACTION	1.8
6HXK	X-RAY DIFFRACTION	1.85
5TDZ	X-RAY DIFFRACTION	2
3MWD	X-RAY DIFFRACTION	2.1
5TDM	X-RAY DIFFRACTION	2.1
3MWE	X-RAY DIFFRACTION	2.2
5TET	X-RAY DIFFRACTION	2.2
7RIG	ELECTRON MICROSCOPY	2.2
8G5C	ELECTRON MICROSCOPY	2.2
5TE1	X-RAY DIFFRACTION	2.25
3PFF	X-RAY DIFFRACTION	2.3
5TEQ	X-RAY DIFFRACTION	2.3
5TES	X-RAY DIFFRACTION	2.4
8G1F	ELECTRON MICROSCOPY	2.4
8G5D	ELECTRON MICROSCOPY	2.5
7RKZ	ELECTRON MICROSCOPY	2.6
7RMP	ELECTRON MICROSCOPY	2.7
8G1E	ELECTRON MICROSCOPY	2.8
6UUW	ELECTRON MICROSCOPY	2.85
7LIW	ELECTRON MICROSCOPY	2.85
7LLA	ELECTRON MICROSCOPY	2.97
6UUZ	ELECTRON MICROSCOPY	3
7LJ9	ELECTRON MICROSCOPY	3
6UI9	ELECTRON MICROSCOPY	3.1
6QFB	X-RAY DIFFRACTION	3.25
9R90	ELECTRON MICROSCOPY	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53396-F1	92.61	0.89

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): 760 (tele-phosphohistidine intermediate)

Ligand- & substrate-binding residues (16): 111; 118; 216; 257; 260; 262; 309; 346; 348; 364; 379; 779–789 …

Post-translational modifications (23): 131, 263, 447, 451, 455, 459, 481, 540, 546, 554, 639, 663, 682, 839, 948, 968, 978, 978, 1077, 1100 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
540	decreased acetylation and increased de novo lipid synthesis; when associated with r,q-546 and r,q-554. abolished ubiquit
546	decreased acetylation and increased de novo lipid synthesis; when associated with r,q-540 and r,q-554. abolished ubiquit
554	decreased acetylation and increased de novo lipid synthesis; when associated with r,q-540 and r,q-546. abolished ubiquit
760	reduced enzyme activity.
978	abolished debenzoylation by sirt3.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-163765	ChREBP activates metabolic gene expression
R-HSA-6798695	Neutrophil degranulation
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 0 (showing top):

GO Biological Process (9): acetyl-CoA biosynthetic process (GO:0006085), citrate metabolic process (GO:0006101), oxaloacetate metabolic process (GO:0006107), fatty acid biosynthetic process (GO:0006633), cholesterol biosynthetic process (GO:0006695), lipid biosynthetic process (GO:0008610), coenzyme A metabolic process (GO:0015936), negative regulation of ferroptosis (GO:0110076), lipid metabolic process (GO:0006629)

GO Molecular Function (8): ATP citrate synthase activity (GO:0003878), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity, acyl groups converted into alkyl on transfer (GO:0046912)

GO Cellular Component (11): extracellular region (GO:0005576), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), azurophil granule lumen (GO:0035578), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), sperm principal piece (GO:0097228), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Metabolism	2
Integration of energy metabolism	1
Innate Immune System	1
Fatty acid metabolism	1
Immune System	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cilium	2
acetyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
tricarboxylic acid metabolic process	1
dicarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
lipid metabolic process	1
biosynthetic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
negative regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
primary metabolic process	1
acyltransferase activity, acyl groups converted into alkyl on transfer	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
catalytic activity	1
acyltransferase activity	1
nuclear lumen	1
cytoplasm	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
microtubule organizing center	1
extracellular vesicle	1
sperm flagellum	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACLY	ACACA	Q13085	900
ACLY	FASN	P49327	895
ACLY	ACSS2	Q9NR19	849
ACLY	ACACB	O00763	828
ACLY	ACSS1	Q9NUB1	827
ACLY	IDH1	O75874	820
ACLY	G6PD	P11413	777
ACLY	CS	O75390	776
ACLY	SREBF1	P36956	776
ACLY	SLC25A1	P53007	775
ACLY	PC	P11498	748
ACLY	ACO2	Q99798	740
ACLY	H6PD	O95479	736
ACLY	IDH2	P48735	734
ACLY	SCD	O00767	729

IntAct

147 interactions, top by confidence:

A	B	Type	Score
PPP2R2A	PPP2R1A	psi-mi:“MI:2364”(proximity)	0.970
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
ATF6	ATF6	psi-mi:“MI:0914”(association)	0.790
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PPP2R2D	ENSA	psi-mi:“MI:0914”(association)	0.570
PPP2R2D	ENSA	psi-mi:“MI:2364”(proximity)	0.570
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PPP2R2B	TCP1	psi-mi:“MI:0914”(association)	0.420
PPP2R2C	BAG2	psi-mi:“MI:0914”(association)	0.420
PPP2R2B	TCP1	psi-mi:“MI:2364”(proximity)	0.420
PPP2R2C	BAG2	psi-mi:“MI:2364”(proximity)	0.420
ACLY	STT3A	psi-mi:“MI:0915”(physical association)	0.400
ACLY	KLHL25	psi-mi:“MI:0915”(physical association)	0.400
ACLY	FXR1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (422): ACLY (Affinity Capture-MS), ACLY (Affinity Capture-Western), ACLY (Affinity Capture-Western), UBR4 (Affinity Capture-Western), SIRT2 (Affinity Capture-Western), ACLY (Affinity Capture-MS), ACLY (Affinity Capture-MS), ACLY (Affinity Capture-MS), ACLY (Affinity Capture-MS), ACLY (Co-fractionation), ACLY (Co-fractionation), ACLY (Co-fractionation), CS (Co-fractionation), HNRNPK (Co-fractionation), NAPRT (Co-fractionation)

ESM2 similar proteins: A0A0D1CLQ4, A0A139AVY4, A9X4T1, B9FK36, C5E4D9, D0MYB4, G5EES6, J9VQZ9, O14134, O42943, O59672, O93796, O94489, P06625, P08240, P16521, P16638, P25997, P29551, P40024, P43535, P53396, P53585, P53978, Q08972, Q2KJA2, Q2TCH3, Q32PF2, Q3MHE8, Q4HY71, Q5KIM6, Q5R9Z5, Q66H39, Q6MG08, Q75EV6, Q767L0, Q7YR37, Q8H0V6, Q8K268, Q8NE71

Diamond homologs: A0A3A6N9V6, B3FHT4, E5Y8P7, O08371, O13750, O19069, O26663, O28098, O28733, O67547, O93988, P09143, P0AGE9, P0AGF0, P0AGF1, P13086, P16638, P36967, P45102, P53396, P53399, P53400, P53401, P53591, P53595, P53596, P53597, P53598, P66866, P68209, P80865, P99070, P9WGC6, P9WGC7, Q1RH56, Q2TCH3, Q32PF2, Q4ULQ8, Q51567, Q54YA0

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
ACLY	“down-regulates quantity by destabilization”	citrate(3-)	“chemical modification”
ACLY	“up-regulates quantity”	oxaloacetate(2-)	“chemical modification”
ACLY	“up-regulates quantity”	acetyl-CoA	“chemical modification”
SREBF1	“up-regulates quantity by expression”	ACLY	“transcriptional regulation”
ACLY	“up-regulates quantity”	ADP(3-)	“chemical modification”
ACLY	“down-regulates quantity by destabilization”	“coenzyme A(4-)”	“chemical modification”
ACLY	“down-regulates quantity by destabilization”	ATP(4-)	“chemical modification”
KLHL25	“down-regulates quantity by destabilization”	ACLY	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	ACLY	binding
LYN	“up-regulates activity”	ACLY	phosphorylation
SRC	“up-regulates activity”	ACLY	phosphorylation
BCKDK	“up-regulates activity”	ACLY	phosphorylation
AKT1	unknown	ACLY	phosphorylation
AKT	unknown	ACLY	phosphorylation
AKT2	unknown	ACLY	phosphorylation
PRKACA	“up-regulates activity”	ACLY	phosphorylation
GSK3B	“up-regulates activity”	ACLY	phosphorylation
MTOR	“up-regulates activity”	ACLY	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Cyclin A/B1/B2 associated events during G2/M transition	5	13.2×	1e-02
Signaling by ALK fusions and activated point mutants	6	7.7×	1e-02
SARS-CoV-2 Infection	8	5.5×	1e-02
SARS-CoV Infections	11	5.2×	7e-03
mRNA Splicing - Major Pathway	10	4.7×	1e-02
Dengue Virus-Host Interactions	11	4.3×	1e-02
Metabolism of RNA	11	3.9×	1e-02
Viral Infection Pathways	13	3.4×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of NLRP3 inflammasome complex assembly	5	20.2×	3e-03
positive regulation of type I interferon production	5	14.6×	7e-03
mRNA splicing, via spliceosome	10	6.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3851 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41868702:GACTC:G	donor_loss	1.0000
17:41868703:ACTCA:A	donor_loss	1.0000
17:41868704:CT:C	donor_loss	1.0000
17:41868705:TCA:T	donor_loss	1.0000
17:41868706:CACCA:C	donor_loss	1.0000
17:41868707:A:AC	donor_gain	1.0000
17:41868707:A:AG	donor_loss	1.0000
17:41868708:C:CC	donor_gain	1.0000
17:41868782:CTCC:C	acceptor_gain	1.0000
17:41868784:CC:C	acceptor_gain	1.0000
17:41868784:CCCT:C	acceptor_loss	1.0000
17:41868785:CC:C	acceptor_gain	1.0000
17:41868785:CCTG:C	acceptor_loss	1.0000
17:41868786:C:CC	acceptor_gain	1.0000
17:41868786:CTG:C	acceptor_loss	1.0000
17:41868787:T:A	acceptor_loss	1.0000
17:41869123:CTT:C	acceptor_gain	1.0000
17:41869126:C:CC	acceptor_gain	1.0000
17:41869469:GTTAC:G	donor_loss	1.0000
17:41869470:TTAC:T	donor_loss	1.0000
17:41869471:TACCT:T	donor_loss	1.0000
17:41869472:A:T	donor_loss	1.0000
17:41869473:CCT:C	donor_loss	1.0000
17:41869499:T:TA	donor_gain	1.0000
17:41869588:C:CC	acceptor_gain	1.0000
17:41871684:CTCA:C	donor_loss	1.0000
17:41871685:TCAC:T	donor_loss	1.0000
17:41871686:CA:C	donor_loss	1.0000
17:41871687:A:AC	donor_gain	1.0000
17:41871688:C:CC	donor_gain	1.0000

AlphaMissense

7242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41867863:G:T	R1085S	1.000
17:41867868:A:T	L1083Q	1.000
17:41867880:A:G	L1079P	1.000
17:41867888:C:A	Q1076H	1.000
17:41867888:C:G	Q1076H	1.000
17:41867902:G:C	H1072D	1.000
17:41867904:C:T	G1071E	1.000
17:41868717:C:T	G1068E	1.000
17:41868718:C:A	G1068W	1.000
17:41868718:C:G	G1068R	1.000
17:41868718:C:T	G1068R	1.000
17:41868722:A:C	S1066R	1.000
17:41868722:A:T	S1066R	1.000
17:41868724:T:G	S1066R	1.000
17:41868725:C:A	R1065S	1.000
17:41868725:C:G	R1065S	1.000
17:41868726:C:A	R1065M	1.000
17:41868726:C:G	R1065T	1.000
17:41868729:C:T	G1064E	1.000
17:41868730:C:G	G1064R	1.000
17:41868730:C:T	G1064R	1.000
17:41868737:A:C	F1061L	1.000
17:41868737:A:T	F1061L	1.000
17:41868739:A:G	F1061L	1.000
17:41869088:C:T	G1030E	1.000
17:41869097:C:T	G1027D	1.000
17:41869098:C:G	G1027R	1.000
17:41869099:A:C	D1026E	1.000
17:41869099:A:T	D1026E	1.000
17:41869100:T:A	D1026V	1.000

dbSNP variants (sampled 300 via entrez): RS1000132345 (17:41917284 G>A), RS1000210375 (17:41868453 A>C,T), RS1000211093 (17:41914335 G>A), RS1000216427 (17:41877438 C>A,T), RS1000353564 (17:41877133 T>G), RS1000412384 (17:41926951 C>T), RS1000463960 (17:41883786 T>C), RS1000512178 (17:41866479 A>G), RS1000554337 (17:41907606 G>A), RS1000689594 (17:41874139 C>T), RS1000729383 (17:41918579 G>A), RS1000746883 (17:41925524 T>C), RS1000797149 (17:41919417 A>C), RS1000863120 (17:41925120 C>T), RS1000953844 (17:41888548 T>A,C)

Disease associations

OMIM: gene MIM:108728 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004612_140	High light scatter reticulocyte percentage of red cells	1.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3720 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Citrate metabolism

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
NDI-091143	Inhibition	8.15	pKd
BMS-303141	Inhibition	6.89	pIC50
bempedoic acid	Inhibition	5.7	pKi

Binding affinities (BindingDB)

50 measured of 93 human assays (93 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
15-chloro-21,23-difluoro-16-hydroxy-8-oxa-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-11-methyl-8-oxa-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-11-methyl-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-11-oxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
5,15-dichloro-21,23-difluoro-16-hydroxy-8,11-dioxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
18-chloro-24,26-difluoro-19-hydroxy-14-oxa-3,21lambda6-dithia-22-azapentacyclo[21.3.1.116,20.02,10.04,9]octacosa-1(27),2(10),4,6,8,16,18,20(28),23,25-decaene-15,21,21-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
4-bromo-15-chloro-21,23-difluoro-16-hydroxy-8,11-dioxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
18-chloro-24,26-difluoro-19-hydroxy-14-oxa-21lambda6-thia-10,22-diazapentacyclo[21.3.1.116,20.02,10.04,9]octacosa-1(27),2,4,6,8,16,18,20(28),23,25-decaene-15,21,21-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-12,18,18-trioxo-8,11-dioxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-4-carbonitrile	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
16-chloro-5,22,24-trifluoro-17-hydroxy-8,12-dioxa-19lambda6-thia-20-azatetracyclo[19.3.11,4,18.02,7]hexacosa-1(25),2,4,6,14,16,18(26),21,23-nonaene-13,19,19-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
14-chloro-20,22-difluoro-15-hydroxy-17lambda6-thia-10,18-diazatetracyclo[17.3.1.112,16.02,7]tetracosa-1(23),2,4,6,12,14,16(24),19,21-nonaene-11,17,17-trione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
16-chloro-22,24-difluoro-17-hydroxy-19,19-dioxo-8-oxa-19λ6-thia-12,20-diazapentacyclo[19.3.1.110,12.114,18.02,7]heptacosa-1(25),2,4,6,14,16,18(26),21,23-nonaen-13-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
21,23-difluoro-18,18-dioxo-8,11-dioxa-18λ6-thia-15,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,17(25),20(24),21-octaene-12,16-dione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
21,23-difluoro-18,18-dioxo-8,11-dioxa-18λ6-thia-16,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,17(25),20(24),21-octaene-12,15-dione	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21-fluoro-16-hydroxy-18,18-dioxo-11-oxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,15,17(25),20(24),21-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-8-methyl-18,18-dioxo-11-oxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,15,17(25),20(24),21-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-8-methyl-18,18-dioxo-11-oxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13(25),14,16,20,22-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21-fluoro-16-hydroxy-23-methoxy-18,18-dioxo-8,11-dioxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13(25),14,16,20(24),21-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
4,15-dichloro-21-fluoro-16-hydroxy-18,18-dioxo-8,11-dioxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,15,17(25),20(24),21-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21-cyclopropyl-16-hydroxy-18,18-dioxo-8,11-dioxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13(25),14,16,20(24),21-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-16-hydroxy-18,18-dioxo-21-(trifluoromethyl)-8,11-dioxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2(7),3,5,13(25),14,16,20,22-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
21-fluoro-16-hydroxy-18,18-dioxo-8,11-dioxa-18λ6-thia-14,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaen-12-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
(6R)-13-chloro-19-fluoro-14-hydroxy-16,16-dioxo-9-oxa-16%6-thia-2,17-diazatetracyclo[16.3.1.111,15.02,6]tricosa-1(21),11(23),12,14,18(22),19-hexaen-10-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
14-chloro-5,20-difluoro-15-hydroxy-17,17-dioxo-10-oxa-17λ6-thia-18-azatetracyclo[17.3.1.112,16.02,7]tetracosa-1(22),2(7),3,5,12,14,16(24),19(23),20-nonaen-11-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
14-chloro-4,20-difluoro-15-hydroxy-17,17-dioxo-10-oxa-17λ6-thia-18-azatetracyclo[17.3.1.112,16.02,7]tetracosa-1(22),2(7),3,5,12(24),13,15,19(23),20-nonaen-11-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
16-chloro-22,24-difluoro-17-hydroxy-19,19-dioxo-12-oxa-19λ6-thia-8,20-diazapentacyclo[19.3.1.18,10.114,18.02,7]heptacosa-1(25),2,4,6,14,16,18(26),21,23-nonaen-13-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-16,16-dioxo-9-oxa-16λ6-thia-3,17-diazatetracyclo[16.3.1.111,15.02,7]tricosa-1(21),2(7),3,5,11,13,15(23),18(22),19-nonaen-10-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21-fluoro-16-hydroxy-11-methyl-18,18-dioxo-8-oxa-18λ6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13(25),14,16,20,22-nonaen-10-one	IC50	60 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
11-chloro-3,5-difluoro-10-hydroxy-18-oxa-8lambda6-thia-7,15-diazatetracyclo[17.3.1.12,6.19,13]pentacosa-1(22),2(25),3,5,9(24),10,12,19(23),20-nonaene-8,8,14-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
11-chloro-3,5-difluoro-10-hydroxy-19-oxa-8lambda6-thia-7,15-diazatetracyclo[18.3.1.12,6.19,13]hexacosa-1(23),2(26),3,5,9(25),10,12,20(24),21-nonaene-8,8,14-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
16-chloro-22,24-difluoro-17-hydroxy-8-oxa-19lambda6-thia-12,20-diazatetracyclo[19.3.1.114,18.02,7]hexacosa-1(25),2,4,6,14,16,18(26),21,23-nonaene-13,19,19-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
(10S)-15-chloro-21,23-difluoro-16-hydroxy-10-methyl-8-oxa-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
(10R)-15-chloro-21,23-difluoro-16-hydroxy-10-methyl-8-oxa-18lambda6-thia-11,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaene-12,18,18-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-4-cyclopropyl-21,23-difluoro-16-hydroxy-8,11-dioxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2,4,6,13(25),14,16,20(24),21-nonaene-12,18,18-trione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
12-chloro-4,6-difluoro-11-hydroxy-9,9-dioxo-2,16-dioxa-9λ6-thia-8-azatetracyclo[16.3.1.13,7.110,14]tetracosa-1(22),3,5,7(24),10(23),11,13,18,20-nonaen-15-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
4,21-difluoro-18,18-dioxo-8,11-dioxa-18λ6-thia-15,19-diazatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13,17(25),20(24),21-octaene-12,16-dione	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-18,18-dioxo-8,11-dioxa-18lambda6-thia-19-azapentacyclo[18.3.1.16,9.113,17.02,7]hexacosa-1(24),2,4,6,13(25),14,16,20,22-nonaen-12-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,23-difluoro-16-hydroxy-8-methyl-18,18-dioxo-11-oxa-18lambda6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13(25),14,16,20,22-nonaen-12-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21,24-difluoro-16-hydroxy-18,18-dioxo-8,11-dioxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(23),2(7),3,5,13(25),14,16,20(24),21-nonaen-12-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
18-chloro-24,26-difluoro-19-hydroxy-21,21-dioxo-11,14-dioxa-21λ6-thia-5,6,22-triazapentacyclo[21.3.1.116,20.02,10.04,8]octacosa-1(27),2(10),3,6,8,16(28),17,19,23,25-decaen-15-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
14-chloro-20-fluoro-17,17-dioxo-10-oxa-17λ6-thia-18-azatetracyclo[17.3.1.112,16.02,7]tetracosa-1(23),2,4,6,12,14,16(24),19,21-nonaen-15-ol	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
20,22-difluoro-15-hydroxy-14-methyl-17,17-dioxo-10-oxa-17λ6-thia-18-azatetracyclo[17.3.1.112,16.02,7]tetracosa-1(23),2,4,6,12,14,16(24),19,21-nonaen-11-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19-fluoro-14-hydroxy-16,16-dioxo-9-oxa-16λ6-thia-17-azatetracyclo[16.3.1.111,15.02,7]tricosa-1(21),2(7),3,5,11(23),12,14,18(22),19-nonaen-10-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-10,16,16-trioxo-9-oxa-16λ6-thia-17-azatetracyclo[16.3.1.111,15.02,7]tricosa-1(21),2,4,6,11(23),12,14,18(22),19-nonaene-4-carbonitrile	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-16,16-dioxo-9-oxa-16λ6-thia-6,17-diazatetracyclo[16.3.1.111,15.02,7]tricosa-1(21),2(7),3,5,11,13,15(23),18(22),19-nonaen-10-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-16,16-dioxo-16λ6-thia-9,17-diazapentacyclo[16.3.1.16,9.111,15.02,7]tetracosa-1(21),2(7),3,5,11,13,15(23),18(22),19-nonaen-10-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-16,16-dioxo-16λ6-thia-6,9,17-triazatetracyclo[16.3.1.111,15.02,7]tricosa-1(22),2,4,6,11,13,15(23),18,20-nonaen-10-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
13-chloro-19,21-difluoro-14-hydroxy-9-methyl-16,16-dioxo-16λ6-thia-9,17-diazatetracyclo[16.3.1.111,15.02,7]tricosa-1(22),2,4,6,11(23),12,14,18,20-nonaen-10-one	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE
15-chloro-21-fluoro-18,18-dioxo-11-oxa-18λ6-thia-19-azatetracyclo[18.3.1.113,17.02,7]pentacosa-1(24),2,4,6,13,15,17(25),20,22-nonaen-16-ol	IC50	5050 nM	US-20250289793: MACROCYCLIC INHIBITORS OF ATP CITRATE LYASE

ChEMBL bioactivities

240 potent at pChembl≥5 of 683 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.68	IC50	2.1	nM	CHEMBL5406616
8.66	Kd	2.2	nM	CHEMBL5406616
7.36	IC50	44	nM	CHEMBL5406616
7.16	IC50	69.7	nM	CHEMBL5439664
6.89	IC50	130	nM	CHEMBL399379
6.89	Kd	128.4	nM	CHEMBL5406616
6.82	IC50	150	nM	CHEMBL118715
6.72	IC50	190	nM	CHEMBL400743
6.66	Ki	220	nM	CHEMBL2163366
6.66	Ki	220	nM	CHEMBL120302
6.56	IC50	275	nM	CHEMBL5822273
6.56	IC50	275	nM	CHEMBL6034869
6.56	IC50	275	nM	CHEMBL5901776
6.56	IC50	275	nM	CHEMBL5751874
6.56	IC50	275	nM	CHEMBL5962773
6.56	IC50	275	nM	CHEMBL5763642
6.56	IC50	275	nM	CHEMBL5784569
6.56	IC50	275	nM	CHEMBL5817088
6.56	IC50	275	nM	CHEMBL5786824
6.56	IC50	275	nM	CHEMBL5954737
6.56	IC50	275	nM	CHEMBL5988531
6.56	IC50	275	nM	CHEMBL5965601
6.56	IC50	275	nM	CHEMBL5962452
6.56	IC50	275	nM	CHEMBL5740498
6.56	IC50	275	nM	CHEMBL5832161
6.56	IC50	275	nM	CHEMBL5808222
6.56	IC50	275	nM	CHEMBL6046481
6.56	IC50	275	nM	CHEMBL5845981
6.56	IC50	275	nM	CHEMBL5961584
6.56	IC50	275	nM	CHEMBL5954786
6.56	IC50	275	nM	CHEMBL5758375
6.56	IC50	275	nM	CHEMBL6040194
6.56	IC50	275	nM	CHEMBL6000371
6.56	IC50	275	nM	CHEMBL5798977
6.56	IC50	275	nM	CHEMBL5901159
6.56	IC50	275	nM	CHEMBL5958556
6.56	IC50	275	nM	CHEMBL5773846
6.56	IC50	275	nM	CHEMBL6001826
6.56	IC50	275	nM	CHEMBL5974091
6.56	IC50	275	nM	CHEMBL5863051
6.56	IC50	275	nM	CHEMBL6062246
6.56	IC50	275	nM	CHEMBL5767000
6.56	IC50	275	nM	CHEMBL5962098
6.56	IC50	275	nM	CHEMBL6037631
6.56	IC50	275	nM	CHEMBL5999264
6.56	IC50	275	nM	CHEMBL5918706
6.56	IC50	275	nM	CHEMBL6002958
6.56	IC50	275	nM	CHEMBL5787145
6.56	IC50	275	nM	CHEMBL5873469
6.56	IC50	275	nM	CHEMBL5828167

PubChem BioAssay actives

94 with measured affinity, of 216 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
methyl 3-chloro-5-[(2,4-difluoro-5-phenylphenyl)sulfamoyl]-4-hydroxybenzoate	1997693: Inhibition of ACLY (unknown origin)	ic50	0.0021	uM
13-chloro-19,21-difluoro-14-hydroxy-16,16-dioxo-16lambda6-thia-9,17-diazatetracyclo[16.3.1.111,15.02,7]tricosa-1(22),2,4,6,11(23),12,14,18,20-nonaen-10-one	1997693: Inhibition of ACLY (unknown origin)	ic50	0.0697	uM
3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	0.1300	uM
(1S,2S)-1,2-dihydroxypropane-1,2,3-tricarboxylic acid	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	0.1500	uM
3,5-dichloro-2-hydroxy-N-(2,4,6-triphenylphenyl)benzenesulfonamide	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	0.1900	uM
(2S)-2-[(2R)-7-(3-chloro-9H-fluoren-9-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	1408678: Inhibition of human ACLY	ki	0.2200	uM
(2R)-2-[(2S)-7-(3-chloro-9H-fluoren-9-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	697048: Inhibition of human recombinant ACLY	ki	0.2200	uM
(2S)-2-[(2R)-8-[4-chloro-2-(3,4-dimethylpyrrol-1-yl)phenyl]-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.3000	uM
(2R)-2-[(2S)-8-[4-chloro-2-(3,4-dimethylpyrrol-1-yl)phenyl]-2-hydroxyoctyl]-2-hydroxybutanedioic acid	697048: Inhibition of human recombinant ACLY	ki	0.3000	uM
[(Z)-3-phenylprop-2-enyl] 2-[(3,5-dichloro-2-hydroxyphenyl)sulfonylamino]benzoate	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	0.3400	uM
(2S)-2-[(2R)-7-(5-chloro-2-phenylindol-1-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.3700	uM
(5-methyl-2-propan-2-ylcyclohexyl) 2-[(3,5-dichloro-2-hydroxyphenyl)sulfonylamino]benzoate	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	0.3700	uM
(2R)-2-[(2S)-7-(5-chloro-2-phenylindol-1-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	697048: Inhibition of human recombinant ACLY	ki	0.3700	uM
(2S,3R)-2-[(2R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2,3-dihydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.5500	uM
(2S,3S)-2-[(2R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2,3-dihydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.6200	uM
(2R,3R)-2-[(2S)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2,3-dihydroxybutanedioic acid	697048: Inhibition of human recombinant ACLY	ki	0.6200	uM
(2R)-1,1-difluoro-2-hydroxypropane-1,2,3-tricarboxylic acid	1408668: Competitive inhibition of human liver ACLY using varying levels of citrate as substrate	ki	0.7000	uM
(2S)-2-[(2R)-7-(3-chlorocarbazol-9-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.7100	uM
(2R)-2-[(2S)-7-(3-chlorocarbazol-9-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	697048: Inhibition of human recombinant ACLY	ki	0.7100	uM
(2S)-2-[(2R)-8-(4-chloro-2-phenylphenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.7500	uM
(2S)-2-[(2R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	0.7700	uM
(2R)-2-[(2R)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	1997694: Binding affinity to ACLY (unknown origin) assessed as inhibition constant	ki	1.0000	uM
(2S)-2-[(2R)-8-(4-chloro-2-phenylmethoxyphenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	1.1000	uM
3,5-dichloro-N-(3,5-ditert-butylphenyl)-2-hydroxybenzenesulfonamide	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	1.1000	uM
2-[8-(2,4-dichlorophenyl)-2-oxooctyl]-2-hydroxybutanedioic acid	1997694: Binding affinity to ACLY (unknown origin) assessed as inhibition constant	ki	1.2000	uM
2-[8-(2,4-dichlorophenyl)octyl]-2-hydroxybutanedioic acid	1997694: Binding affinity to ACLY (unknown origin) assessed as inhibition constant	ki	1.2000	uM
2-[6-(2,4-dichlorophenyl)hexylsulfanylmethyl]-2-hydroxybutanedioic acid	1997694: Binding affinity to ACLY (unknown origin) assessed as inhibition constant	ki	1.2000	uM
2-[6-(2,4-dichlorophenyl)hexylsulfanylmethyl]butanedioic acid	1997694: Binding affinity to ACLY (unknown origin) assessed as inhibition constant	ki	1.2000	uM
(2S)-2-[(2R)-7-(5,7-dichloroindol-1-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	1.8000	uM
(1S,4R,5R,9R,10R,12R,14R)-14-[(4R)-4-[(1’S,3R,5aR,9aS)-1’,6,6-trimethyl-3’-methylidene-7-oxospiro[1,2,4,5,5a,8,9,9a-octahydrocyclopenta[a]naphthalene-3,2’-cyclopentane]-1’-yl]-2-oxopentyl]-5,9-dimethyl-16-propan-2-yltetracyclo[10.2.2.01,10.04,9]hexadec-15-ene-5,14-dicarboxylic acid	1968747: Inhibition of ACL (unknown origin) incubated for 30 mins in presence of ATP by luminescence based ADP-Glo kinase assay	ic50	1.8000	uM
(2S)-2-[(2S)-8-(2,4-dichlorophenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	2.0000	uM
3,5-dichloro-N-(3,5-dichlorophenyl)-2-hydroxybenzenesulfonamide	307170: Inhibition of human recombinant ATP-citrate lyase	ic50	2.3000	uM
(1S,4R,5R,9R,10R,12R,14S)-5,9-dimethyl-14-[(4R)-2-oxo-4-[(5R,10S,13R,14R,17R)-4,4,13,14-tetramethyl-3-oxo-2,5,6,7,10,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl]pentyl]-16-propan-2-yltetracyclo[10.2.2.01,10.04,9]hexadec-15-ene-5,14-dicarboxylic acid	1968747: Inhibition of ACL (unknown origin) incubated for 30 mins in presence of ATP by luminescence based ADP-Glo kinase assay	ic50	2.6000	uM
(2S)-2-[(2R)-8-[4-chloro-2-(4-methylphenyl)phenyl]-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	2.7000	uM
(2S)-2-[(2R)-8-[4-chloro-2-(4-fluorophenyl)phenyl]-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	2.7000	uM
7-[[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-2,3,4,7,8,8a-hexahydronaphthalen-1-yl]methyl]-1,3-benzoxazol-5-ol	1616398: Inhibition of ACL (unknown origin)	ic50	2.8000	uM
7-[[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-2,3,4,7,8,8a-hexahydronaphthalen-1-yl]methyl]-5-hydroxy-3H-1,3-benzoxazol-2-one	1616398: Inhibition of ACL (unknown origin)	ic50	2.8000	uM
8-[[(1R,2S,4aS,8aS)-1,2,4a-trimethyl-5-methylidene-3,4,6,7,8,8a-hexahydro-2H-naphthalen-1-yl]methyl]-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-6-ol	1616398: Inhibition of ACL (unknown origin)	ic50	2.8000	uM
8-[[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-2,3,4,7,8,8a-hexahydronaphthalen-1-yl]methyl]-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-6-ol	1616398: Inhibition of ACL (unknown origin)	ic50	2.8000	uM
1,3-dibromo-2,4,5-trihydroxy-7-methylanthracene-9,10-dione	1434016: Inhibition of ATP citrate lyase (unknown origin) using sodium citrate as substrate after 60 mins by ADP-Glo luminescence assay	ic50	2.9000	uM
(2S)-2-[(2R)-7-(6-chloro-1,2,3,4-tetrahydrocarbazol-9-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	2.9000	uM
(2S)-2-[(2R)-7-(3-benzyl-5-chloroindol-1-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	2.9000	uM
(2S)-2-[(2R)-8-(5-chloroindol-1-yl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	3.2000	uM
(2S)-1,1-difluoro-2-hydroxypropane-1,2,3-tricarboxylic acid	1408668: Competitive inhibition of human liver ACLY using varying levels of citrate as substrate	ki	3.2000	uM
(1S,4R,5R,9R,10R,12R,14S)-14-[(4R)-4-[(1’S,3R,5aR,9aS)-1’,6,6-trimethyl-3’-methylidene-7-oxospiro[1,2,4,5,5a,8,9,9a-octahydrocyclopenta[a]naphthalene-3,2’-cyclopentane]-1’-yl]-2-oxopentyl]-5,9-dimethyl-16-propan-2-yltetracyclo[10.2.2.01,10.04,9]hexadec-15-ene-5,14-dicarboxylic acid	1968747: Inhibition of ACL (unknown origin) incubated for 30 mins in presence of ATP by luminescence based ADP-Glo kinase assay	ic50	3.3000	uM
(2S)-2-[(2R)-7-(5-chloroindol-1-yl)-2-hydroxyheptyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	3.5000	uM
(1S,4R,5R,9R,10R,12R,13R,14S)-13-[(3R)-3-[(1’S,3R,5aR,9aS)-1’,6,6,9a-tetramethyl-3’-methylidene-7-oxospiro[2,4,5,5a,8,9-hexahydro-1H-cyclopenta[a]naphthalene-3,2’-cyclopentane]-1’-yl]butanoyl]-5,9,14-trimethyl-16-propan-2-yltetracyclo[10.2.2.01,10.04,9]hexadec-15-ene-5,14-dicarboxylic acid	1968747: Inhibition of ACL (unknown origin) incubated for 30 mins in presence of ATP by luminescence based ADP-Glo kinase assay	ic50	3.6000	uM
4-chloro-1,3,8-trihydroxy-6-methyl-10H-anthracen-9-one	1434016: Inhibition of ATP citrate lyase (unknown origin) using sodium citrate as substrate after 60 mins by ADP-Glo luminescence assay	ic50	3.8000	uM
(2S)-2-[(2R)-8-(4-chloro-2-pyrrol-1-ylphenyl)-2-hydroxyoctyl]-2-hydroxybutanedioic acid	32379: Inhibitory activity against human recombinant ATP-Citrate Lyase (ACL) enzyme	ki	3.9000	uM
5-methyl-4-[(2-oxo-4-phenyl-6-propylchromen-7-yl)oxymethyl]furan-2-carboxylic acid	1434770: Inhibition of ATP citrate lyase (unknown origin) using sodium citrate as substrate by ADP-Glo luminescence assay	ic50	4.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
fatostatin	decreases expression, increases response to substance, increases reaction	5
sodium arsenite	decreases expression, increases abundance, affects expression	4
bisphenol A	affects expression, decreases expression	2
cobaltous chloride	decreases expression	2
bisphenol S	increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects reaction, increases expression, affects expression	2
Oleic Acid	affects cotreatment, decreases expression, increases abundance	2
Genistein	increases expression, decreases expression, increases reaction	2
brexpiprazole	decreases expression	1
afuresertib	increases expression	1
FR900359	affects phosphorylation	1
darolutamide	decreases expression, decreases reaction	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
beta-thujone	affects cotreatment, decreases expression	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
hydroxyhydroquinone	increases expression	1
spathulenol	decreases expression, affects cotreatment	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
linalool	affects cotreatment, decreases expression	1
caryophyllene	affects cotreatment, decreases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1

ChEMBL screening assays

53 unique, capped per target: 53 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2169035	Binding	Inhibition of human recombinant ACLY	The lipogenesis pathway as a cancer target. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1V3	Abcam A-549 ACLY KO	Cancer cell line	Male
CVCL_D1ZR	Abcam HCT 116 ACLY KO	Cancer cell line	Male
CVCL_D7JD	Ubigene A-549 ACLY KO	Cancer cell line	Male
CVCL_E1AI	Ubigene PANC-1 ACLY KO	Cancer cell line	Male
CVCL_SB23	HAP1 ACLY (-) 1	Cancer cell line	Male
CVCL_XK97	HAP1 ACLY (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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