ACACB

Summary

ACACB (acetyl-CoA carboxylase beta, HGNC:85) is a protein-coding gene on chromosome 12q24.11, encoding Acetyl-CoA carboxylase 2 (O00763). Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism.

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis.

Source: NCBI Gene 32 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated cleft palate (Limited, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 569 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001093

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:85
Approved symbol	ACACB
Name	acetyl-CoA carboxylase beta
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	HACC275, ACC2, ACCB, ACC-beta, ACCbeta, ACACbeta
Ensembl gene	ENSG00000076555
Ensembl biotype	protein_coding
OMIM	601557
Entrez	32

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 retained_intron, 5 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000338432, ENST00000377848, ENST00000377854, ENST00000396233, ENST00000534852, ENST00000536440, ENST00000537279, ENST00000537347, ENST00000538526, ENST00000539864, ENST00000542524, ENST00000543080, ENST00000544651, ENST00000544726, ENST00000546328

RefSeq mRNA: 7 — MANE Select: NM_001093 NM_001093, NM_001412734, NM_001412735, NM_001412736, NM_001412737, NM_001412738, NM_001412739

CCDS: CCDS31898

Canonical transcript exons

ENST00000338432 — 53 exons

Exon	Start	End
ENSE00000410836	109237165	109237380
ENSE00000754740	109233748	109233847
ENSE00000754741	109233938	109234045
ENSE00000754742	109235313	109235369
ENSE00000754743	109235606	109235647
ENSE00000754745	109241078	109241281
ENSE00000754752	109253015	109253158
ENSE00000754753	109254214	109254334
ENSE00000754755	109256140	109256236
ENSE00000754756	109258268	109258364
ENSE00000754757	109258973	109259108
ENSE00000834688	109247606	109247703
ENSE00001507550	109242437	109242592
ENSE00002235090	109116587	109116704
ENSE00002248873	109216796	109216920
ENSE00002312587	109216618	109216706
ENSE00002318749	109266236	109268226
ENSE00002414906	109239830	109239985
ENSE00003466998	109265389	109265525
ENSE00003559754	109232669	109232806
ENSE00003598675	109264232	109264386
ENSE00003607535	109265110	109265280
ENSE00003633552	109252046	109252156
ENSE00003648656	109262357	109262469
ENSE00003666060	109245626	109245748
ENSE00003674468	109260480	109260657
ENSE00003681964	109176153	109176263
ENSE00003692777	109249984	109250104
ENSE00003711752	109179917	109180087
ENSE00003712327	109246179	109246448
ENSE00003713917	109179088	109179297
ENSE00003715175	109185579	109185740
ENSE00003715301	109227371	109227489
ENSE00003716931	109222507	109222620
ENSE00003717197	109171805	109171914
ENSE00003722000	109191847	109191950
ENSE00003725709	109139397	109140058
ENSE00003726799	109166861	109166993
ENSE00003728112	109212836	109212936
ENSE00003729382	109172275	109172356
ENSE00003729412	109222799	109222912
ENSE00003731216	109187999	109188162
ENSE00003732315	109223815	109223904
ENSE00003732419	109193648	109193729
ENSE00003733707	109175931	109176040
ENSE00003737429	109199402	109199552
ENSE00003737693	109209165	109209353
ENSE00003745712	109167896	109168034
ENSE00003745866	109191613	109191763
ENSE00003748551	109174132	109174230
ENSE00003754435	109197008	109197153
ENSE00003754629	109201567	109201701
ENSE00003754769	109206710	109206856

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1992 / max 2046.7781, expressed in 957 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127929	9.1512	174
127930	3.9813	160
127935	2.8392	731
127933	0.5175	270
127928	0.4740	80
127925	0.4437	59
127936	0.3080	152
127927	0.2362	51
127924	0.2344	57
127922	0.2338	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.00	gold quality
adipose tissue	UBERON:0001013	98.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.05	gold quality
mucosa of stomach	UBERON:0001199	97.81	gold quality
renal medulla	UBERON:0000362	97.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.62	gold quality
connective tissue	UBERON:0002384	97.59	gold quality
omental fat pad	UBERON:0010414	97.52	gold quality
peritoneum	UBERON:0002358	97.48	gold quality
pericardium	UBERON:0002407	97.46	gold quality
gastrocnemius	UBERON:0001388	97.36	gold quality
muscle of leg	UBERON:0001383	96.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.66	gold quality
apex of heart	UBERON:0002098	96.56	gold quality
medial globus pallidus	UBERON:0002477	95.82	gold quality
muscle organ	UBERON:0001630	95.66	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.06	gold quality
sural nerve	UBERON:0015488	95.03	gold quality
lower esophagus	UBERON:0013473	95.01	gold quality
skeletal muscle tissue	UBERON:0001134	94.96	gold quality
synovial joint	UBERON:0002217	94.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.83	gold quality
liver	UBERON:0002107	94.79	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.72	gold quality
deltoid	UBERON:0001476	94.43	gold quality
gluteal muscle	UBERON:0002000	94.37	gold quality
adrenal tissue	UBERON:0018303	94.32	gold quality
globus pallidus	UBERON:0001875	94.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	11146.67
E-ANND-3	yes	9.04
E-HCAD-25	yes	4.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, MYF6, MYOD1, MYOG, NRF1, RARA, RXRA, SP1, SREBF1, USF1

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981

Literature-anchored findings (GeneRIF, showing 40)

• The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles. (PMID:22701718)
• binding of T4 gene 32 protein to single- and double-stranded DNA is electrostatically regulated (PMID:15994897)
• UvsW-catalyzed unwinding of recombination intermediates such as D-loops and static X-DNA (Holliday junction mimic) to ssDNA products is enhanced by the gp32 protein. (PMID:23732982)
• Gp59-DNA interactions are needed to load Gp41 onto nascent or collapsed replication forks lacking clusters of Gp32 and to coordinate bidirectional replication from T4 origins. (PMID:24338568)
• Characterization of structural and thermodynamic aspects of gp32 binding cooperativity that are central to the function of this single stranded DNA binding protein with the T4 DNA replication. (PMID:26275774)
• The results show that single gp32 molecules interact most directly and specifically near the 3’-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2-3 nts are directly involved in this tight binding interaction. (PMID:26275775)
• the C-domain of bacteriophage T4 gene 32 protein has a role in ssDNA binding and dsDNA helix-destabilization (PMID:29634784)
• Dynamic structure of T4 gene 32 protein filaments facilitates rapid noncooperative protein dissociation. (PMID:37449435)
• The effect of a 3-month low-intensity endurance training program on fat oxidation and expression (PMID:12086953)
• elevation of AMPK via phosphorylation is not sufficient to maintain elevated ACCbeta Ser(221) phosphorylation during exercise (PMID:12413941)
• down-regulation of acetyl coa carboxylase 2 (ACC2) mRNA, induced by the lowering of plasma insulin concentration, is related to improvement of insulin sensitivity (PMID:14627750)
• differential regulation of ACCbeta gene expression between tissues (PMID:15590647)
• The expression, purification, and characterization of ACC2 were investigated. (PMID:17223360)
• observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors (PMID:17521700)
• Differential activation of recombinant ACC1 and ACC2 by citrate is reported. (PMID:18455495)
• Human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. (PMID:19190759)
• The human ACC2 CT-domain C-terminus is comprised of three intertwined alpha-helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. (PMID:19390150)
• results point towards major differences in ACC tissue distribution between humans and rats (PMID:19618481)
• the crystal structures of the biotin carboxylase domain of human ACC2 phosphorylated by AMP-activated protein kinase was reported. (PMID:19900410)
• data suggest that insulin and glucocorticoid have positive effects on both acetyl-CoA carboxylase alpha(ACC1) and beta(ACC2) gene transcription (PMID:20139635)
• These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes. (PMID:20168990)
• ACACB overexpression in renal proximal tubular epithelial cell increased proinflammatory cytokine expression, such as IL-6, at least partly by increasing mRNA stability through a p38 MAPK-dependent pathway. (PMID:20514549)
• The acetyl-coenzyme A carboxylase beta (ACACB) gene is associated with nephropathy in Chinese patients with type 2 diabetes. (PMID:20519229)
• This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACCbeta gene promoter in the mammalian heart. (PMID:20599696)
• The -368 C/T single-nucleotide polymorphism in ACACB P-II binds HepG2 nuclear proteins that affect promoter activity in an allele-specific fashion. (PMID:20799892)
• Acetyl-CoA carboxylase beta (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. (PMID:20855566)
• A gene polymorphism in acetyl-coenzyme A carboxylase beta may be associated with the C-reactive protein level in a prediabetic and diabetic population. (PMID:21553357)
• Common variants within the ACACB locus appear to regulate adipose gene expression (PMID:21887335)
• In conclusion, common polymorphisms of ACACB gene are associated with obesity and, independently, with type 2 diabetes in postmenopausal women (PMID:21908218)
• Structure-guided inhibitor design for human acetyl-coenzyme A carboxylase by interspecies active site conversion. (PMID:21953464)
• TT genotypes of ACACB gene (rs2268388) and CC genotype of AGTR1 gene (rs5186) confers the risk of diabetic nephropathy in Asian Indian patients with T2DM. (PMID:23081748)
• Its involvement in the development of diabetic nephropathy is explained by the promotion of the so-called micro-inflammation associated with the diabetic state. (PMID:23156397)
• These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to diabetic nephropathy. (PMID:23460794)
• Our meta-analysis supports that the apolipoprotein E epsilon2 allele and acetyl-CoA carboxylase beta rs2268388 C>T might act as promotion factors of nephropathy in type 2 diabetes. (PMID:25262148)
• The knockdown of ACC2 reduced palmitic acid -induced autophagy and thus protects the cells from palmitic acid - induced lipotoxicity with attenuated lipid accumulation and rescued cell viability. (PMID:26022126)
• A significant association exists of ACACB gene polymorphism and diabetic nephropathy among Caucasian patients with diabetes. (PMID:26030797)
• PHD3 loss in cancer enables metabolic reliance on fatty acid oxidation via deactivation of ACC2. (PMID:27635760)
• Cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. (PMID:27693630)
• Inhibition of Acetyl-CoA Carboxylase 1 (ACC1) and 2 (ACC2) Reduces Proliferation and De Novo Lipogenesis of EGFRvIII Human Glioblastoma Cells (PMID:28081256)
• ACC2 gene (ACACB) expression was decreased by 25% in HCC tissue compared to non-cancerous liver tissue. (PMID:28290443)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acacb	ENSDARG00000061994
mus_musculus	Acacb	ENSMUSG00000042010
rattus_norvegicus	Acacb	ENSRNOG00000000658
drosophila_melanogaster	ACC	FBGN0033246

Paralogs (4): MCCC1 (ENSG00000078070), PC (ENSG00000173599), PCCA (ENSG00000175198), ACACA (ENSG00000278540)

Protein

Protein identifiers

Acetyl-CoA carboxylase 2 — O00763 (reviewed: O00763)

Alternative names: ACC-beta

All UniProt accessions (6): O00763, A0A087WUA1, F5H5C3, F8W8T8, H0YGH5, S4R3S7

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation. Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage.

Subunit / interactions. Monomer, homodimer, and homotetramer. Forms filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity in a citrate-dependent manner.

Subcellular location. Mitochondrion.

Tissue specificity. Widely expressed with highest levels in heart, skeletal muscle, liver, adipose tissue, mammary gland, adrenal gland and colon. Isoform 3 is expressed in skeletal muscle, adipose tissue and liver (at protein level). Isoform 3 is detected at high levels in adipose tissue with lower levels in heart, liver, skeletal muscle and testis.

Post-translational modifications. The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity. Phosphorylation at Ser-222 by AMPK inactivates the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis.

Activity regulation. Activity is increased by oligomerization of the protein into filaments. The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-222. Inhibited by its product, malonyl-CoA. Activated by citrate. Activation by MID1IP1 is citrate-dependent. Soraphen A, inhibits the enzyme by preventing the formation of active filamentous oligomers.

Cofactor. Binds 2 magnesium or manganese ions per subunit.

Domain organisation. Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain. The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA.

Pathway. Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.

Isoforms (3)

UniProt ID	Names	Canonical?
O00763-1	1, Long	yes
O00763-2	2, Short
O00763-3	3, ACC2.v2

RefSeq proteins (7): NP_001084, NP_001399663, NP_001399664, NP_001399665, NP_001399666, NP_001399667, NP_001399668 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000089	Biotin_lipoyl	Domain
IPR005479	CPAse_ATP-bd	Domain
IPR005481	BC-like_N	Domain
IPR005482	Biotin_COase_C	Domain
IPR011053	Single_hybrid_motif	Homologous_superfamily
IPR011054	Rudment_hybrid_motif	Homologous_superfamily
IPR011761	ATP-grasp	Domain
IPR011762	COA_CT_N	Domain
IPR011763	COA_CT_C	Domain
IPR011764	Biotin_carboxylation_dom	Domain
IPR013537	AcCoA_COase_cen	Domain
IPR013815	ATP_grasp_subdomain_1	Homologous_superfamily
IPR016185	PreATP-grasp_dom_sf	Homologous_superfamily
IPR029045	ClpP/crotonase-like_dom_sf	Homologous_superfamily
IPR034733	AcCoA_carboxyl_beta	Domain
IPR049074	ACCA_BT	Domain
IPR049076	ACCA	Family

Pfam: PF00289, PF00364, PF01039, PF02785, PF02786, PF08326, PF21385

Enzyme classification (BRENDA):

• EC 6.3.4.14 — biotin carboxylase (BRENDA: 52 organisms, 95 substrates, 41 inhibitors, 87 Km, 31 kcat entries)
• EC 6.4.1.2 — acetyl-CoA carboxylase (BRENDA: 88 organisms, 133 substrates, 705 inhibitors, 131 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

18 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–1.2	39
ATP	0.015–0.5	38
BIOTIN	22.7–1234	31
HCO3-	0.3–12.8	27
ATP	0.0025–21	18
HCO3-	0.37–57.5	17
ADP	0.0013–0.83	8
CARBAMOYL PHOSPHATE	0.51–11.2	5
MALONYL-COA	0.016–0.75	5
PROPIONYL-COA	0.045–0.144	4
BIOCYTIN	10–70	2
BIOTIN	0.1–3	2
BUTYRYL-COA	0.099–0.143	2
BIOTIN-CARBOXYL-CARRIER PROTEIN	0.16	1
CO2	62.2	1

Catalyzed reactions (Rhea), 1 shown:

• hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H(+) (RHEA:11308)

UniProt features (184 total): helix 58, strand 56, modified residue 19, binding site 12, turn 8, sequence conflict 8, domain 5, sequence variant 4, compositionally biased region 3, splice variant 3, region of interest 3, mutagenesis site 2, transit peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
3GLK	X-RAY DIFFRACTION	2.1
3GID	X-RAY DIFFRACTION	2.3
3TDC	X-RAY DIFFRACTION	2.41
2HJW	X-RAY DIFFRACTION	2.5
3JRX	X-RAY DIFFRACTION	2.5
3JRW	X-RAY DIFFRACTION	2.6
5KKN	X-RAY DIFFRACTION	2.6
4HQ6	X-RAY DIFFRACTION	2.7
3FF6	X-RAY DIFFRACTION	3.19
2DN8	SOLUTION NMR
2KCC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00763-F1	79.29	0.29

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): 584

Ligand- & substrate-binding residues (12): 458–463; 567; 567; 580; 580; 580; 580; 582; 582; 1934; 2238; 2240

Post-translational modifications (19): 35, 70, 91, 95, 169, 175, 192, 195, 200, 207, 220, 222, 469, 753, 929, 1340, 1342, 1360, 1405

Mutagenesis-validated functional residues (2):

Position	Phenotype
277	loss of regulation of oligomerization by phosphorylation at s-222.
671	altered regulation of oligomerization by phosphorylation at s-222.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-163765	ChREBP activates metabolic gene expression
R-HSA-196780	Biotin transport and metabolism
R-HSA-200425	Carnitine shuttle
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 255 (showing top): GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, WANG_CLIM2_TARGETS_UP, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_HEART_GROWTH, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS

GO Biological Process (28): acetyl-CoA metabolic process (GO:0006084), pentose-phosphate shunt (GO:0006098), fatty acid biosynthetic process (GO:0006633), response to nutrient (GO:0007584), response to xenobiotic stimulus (GO:0009410), positive regulation of lipid storage (GO:0010884), regulation of glucose metabolic process (GO:0010906), fatty acid oxidation (GO:0019395), negative regulation of fatty acid beta-oxidation (GO:0031999), obsolete D-glucose import (GO:0046323), lactic acid secretion (GO:0046722), protein homotetramerization (GO:0051289), fatty acid homeostasis (GO:0055089), positive regulation of heart growth (GO:0060421), response to caloric restriction (GO:0061771), tricarboxylic acid metabolic process (GO:0072350), intracellular aspartate homeostasis (GO:0090459), intracellular glutamate homeostasis (GO:0090461), energy homeostasis (GO:0097009), regulation of cardiac muscle hypertrophy in response to stress (GO:1903242), malonyl-CoA biosynthetic process (GO:2001295), purine nucleotide metabolic process (GO:0006163), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), response to nutrient levels (GO:0031667), negative regulation of fatty acid oxidation (GO:0046322), negative regulation of lipid catabolic process (GO:0050995)

GO Molecular Function (9): acetyl-CoA carboxylase activity (GO:0003989), ATP binding (GO:0005524), biotin binding (GO:0009374), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (5): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), mitochondrial fatty acid beta-oxidation multienzyme complex (GO:0016507)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Metabolism	3
Metabolism of lipids	2
Integration of energy metabolism	1
Metabolism of water-soluble vitamins and cofactors	1
Fatty acid metabolism	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Metabolism of steroids	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	2
response to nutrient levels	2
response to chemical	2
intracellular amino acid homeostasis	2
heterocyclic compound binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
acyl-CoA metabolic process	1
NADPH regeneration	1
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
lipid oxidation	1
fatty acid beta-oxidation	1
regulation of fatty acid beta-oxidation	1
negative regulation of fatty acid oxidation	1
negative regulation of lipid catabolic process	1
plasma membrane lactate transport	1
acid secretion	1
protein homooligomerization	1
protein tetramerization	1
lipid homeostasis	1
positive regulation of organ growth	1
heart growth	1
regulation of heart growth	1
response to stress	1
carboxylic acid metabolic process	1
multicellular organismal-level homeostasis	1
regulation of cardiac muscle hypertrophy	1
regulation of cardiac muscle adaptation	1
cardiac muscle hypertrophy in response to stress	1

Protein interactions and networks

STRING

2766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACACB	FASN	P49327	909
ACACB	CPT1A	P50416	879
ACACB	ACLY	P53396	828
ACACB	SREBF1	P36956	764
ACACB	ACOX1	Q15067	723
ACACB	ACSL1	P33121	717
ACACB	SCARB1	Q8WTV0	704
ACACB	EHHADH	Q08426	681
ACACB	CLPP	Q16740	672
ACACB	SCD	O00767	664
ACACB	ACSL3	O95573	657
ACACB	FABP3	P05413	654
ACACB	HMGCR	P04035	606
ACACB	HADHB	P55084	605
ACACB	MCAT	Q8IVS2	597

IntAct

74 interactions, top by confidence:

A	B	Type	Score
Mid1ip1	ACACB	psi-mi:“MI:0407”(direct interaction)	0.640
HLCS	ACACB	psi-mi:“MI:0414”(enzymatic reaction)	0.620
HLCS	ACACB	psi-mi:“MI:0407”(direct interaction)	0.620
ACACB	ACACB	psi-mi:“MI:0407”(direct interaction)	0.560
MLF1	HAX1	psi-mi:“MI:0914”(association)	0.560
Zfp36	CNOT1	psi-mi:“MI:0914”(association)	0.560
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
MID1IP1	ACACB	psi-mi:“MI:0914”(association)	0.530
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
PEX14	ACACB	psi-mi:“MI:0407”(direct interaction)	0.440
ACACB	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
RGS1	ACACB	psi-mi:“MI:0915”(physical association)	0.400
BCDIN3D	ACACB	psi-mi:“MI:0915”(physical association)	0.400
ACACB	MOXD1	psi-mi:“MI:0915”(physical association)	0.400
DUSP22	ACACB	psi-mi:“MI:0914”(association)	0.350
PPM1H	ACACB	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
STK25	ACACB	psi-mi:“MI:0914”(association)	0.350
DAPK3	ACACB	psi-mi:“MI:0914”(association)	0.350
OXSR1		psi-mi:“MI:0914”(association)	0.350
WHR1	ACACB	psi-mi:“MI:0914”(association)	0.350
CDK7	ACACB	psi-mi:“MI:0914”(association)	0.350
CDKL1	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (151): ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Proximity Label-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Affinity Capture-MS), ACACB (Proximity Label-MS), ACACB (Proximity Label-MS), ACACB (Affinity Capture-RNA)

ESM2 similar proteins: A0A1S3YEG8, A0A1S4BJT3, A7M6E7, A7M6E8, B2RFT0, B4G0F3, B5WWZ8, B5WWZ9, E0CTF3, E9Q4Z2, F4JVN6, H9BFW7, K7WIZ6, O00763, O74351, O82663, P31039, P32296, P69060, P93568, Q02166, Q0QF01, Q10D00, Q28ED0, Q3SZM5, Q5R6R5, Q5Z856, Q6PA58, Q6TAS3, Q6Z836, Q6ZDY8, Q6ZHE5, Q801S2, Q8K2B3, Q8L5Z4, Q8LPN3, Q8NFW8, Q8ZD80, Q91WT9, Q93Z70

Diamond homologs: A0A0H3JRU9, A0A4P8DJE6, A2C2S8, A5H0J2, A6ZMR9, B3LM95, B8G187, B9HBA8, B9N843, C0H419, C7GRE4, C8ZF72, D3DJ41, D3DJ42, E9Q4Z2, I3R7G3, O00763, O04983, O17732, O27179, O27939, O30019, O34544, O52058, O93918, P05115, P05165, P06959, P0A509, P0DTA4, P10802, P11154, P11497, P11498, P13187, P14882, P24182, P29337, P32327, P32528

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKAA2	“down-regulates activity”	ACACB	phosphorylation
ACACB	“down-regulates quantity”	acetyl-CoA	“chemical modification”
ACACB	“up-regulates quantity”	malonyl-CoA	“chemical modification”
COP1	“down-regulates quantity by destabilization”	ACACB	ubiquitination
TRIB3	“down-regulates quantity by destabilization”	ACACB	binding
MID1IP1	“up-regulates activity”	ACACB	binding
TFEB	“up-regulates quantity by expression”	ACACB	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein phosphorylation	9	9.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	395
Likely benign	77
Benign	32

Top pathogenic / likely-pathogenic (0)

SpliceAI

8413 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109166950:C:G	donor_gain	1.0000
12:109166991:AAGGT:A	donor_loss	1.0000
12:109166992:AG:A	donor_loss	1.0000
12:109166993:GGTA:G	donor_loss	1.0000
12:109166995:T:A	donor_loss	1.0000
12:109167891:TGCAG:T	acceptor_loss	1.0000
12:109167892:GCAGG:G	acceptor_loss	1.0000
12:109167893:CAGG:C	acceptor_loss	1.0000
12:109167894:AGGTG:A	acceptor_loss	1.0000
12:109167895:GGT:G	acceptor_gain	1.0000
12:109167895:GGTGC:G	acceptor_gain	1.0000
12:109168016:GACCT:G	donor_gain	1.0000
12:109168030:CGCAG:C	donor_loss	1.0000
12:109168032:CAGGT:C	donor_loss	1.0000
12:109168033:AGG:A	donor_loss	1.0000
12:109168034:GG:G	donor_loss	1.0000
12:109168036:T:G	donor_loss	1.0000
12:109171797:A:AG	acceptor_gain	1.0000
12:109171798:A:G	acceptor_gain	1.0000
12:109171803:A:AG	acceptor_gain	1.0000
12:109171804:G:GA	acceptor_gain	1.0000
12:109171804:GA:G	acceptor_gain	1.0000
12:109171804:GAGT:G	acceptor_gain	1.0000
12:109171914:GG:G	donor_loss	1.0000
12:109171915:GTAG:G	donor_loss	1.0000
12:109171930:TGCCC:T	donor_gain	1.0000
12:109174121:C:CA	acceptor_gain	1.0000
12:109174228:GCG:G	donor_gain	1.0000
12:109176147:A:AG	acceptor_gain	1.0000
12:109176152:GGCA:G	acceptor_gain	1.0000

AlphaMissense

16205 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109172290:T:A	W351R	1.000
12:109172290:T:C	W351R	1.000
12:109167900:T:C	L264P	0.999
12:109167914:G:T	G269W	0.999
12:109167948:G:C	R280P	0.999
12:109167953:T:A	W282R	0.999
12:109167953:T:C	W282R	0.999
12:109171838:T:A	V320D	0.999
12:109172281:T:A	W348R	0.999
12:109172281:T:C	W348R	0.999
12:109172292:G:C	W351C	0.999
12:109172292:G:T	W351C	0.999
12:109180083:T:C	L605P	0.999
12:109185708:G:C	A650P	0.999
12:109188038:T:C	F674L	0.999
12:109188039:T:C	F674S	0.999
12:109188040:C:A	F674L	0.999
12:109188040:C:G	F674L	0.999
12:109188059:T:A	W681R	0.999
12:109188059:T:C	W681R	0.999
12:109188063:G:A	G682D	0.999
12:109188071:A:C	S685R	0.999
12:109188073:C:A	S685R	0.999
12:109188073:C:G	S685R	0.999
12:109188120:G:A	G701E	0.999
12:109188155:G:C	A713P	0.999
12:109209229:T:C	L1042P	0.999
12:109222616:G:C	R1225P	0.999
12:109239881:G:C	A1572P	0.999
12:109239894:T:C	L1576P	0.999

dbSNP variants (sampled 300 via entrez): RS1000002049 (12:109115197 C>T), RS1000028032 (12:109170083 C>A,T), RS1000096007 (12:109159961 G>A), RS1000124815 (12:109119751 G>T), RS1000126074 (12:109140032 A>G), RS1000156340 (12:109241912 A>G), RS1000159841 (12:109183053 C>A), RS1000175016 (12:109224101 G>A), RS1000192357 (12:109235528 A>C,G), RS1000199676 (12:109223745 T>C,G), RS1000215706 (12:109233075 A>T), RS1000238323 (12:109199675 G>A), RS1000242864 (12:109199903 T>C), RS1000265843 (12:109112263 C>A,G), RS1000268577 (12:109224390 C>T)

Disease associations

OMIM: gene MIM:601557 | disease phenotypes: MIM:608106

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated cleft palate	Limited	Unknown

Mondo (4): hyper-IgM syndrome type 5 (MONDO:0011971), primary ovarian failure (MONDO:0005387), autism spectrum disorder (MONDO:0005258), isolated cleft palate (MONDO:0007336)

Orphanet (3): Hyper-IgM syndrome type 5 (Orphanet:101092), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST006613_57	Triglycerides	3.000000e-08
GCST010135_11	Oily fish consumption	6.000000e-11
GCST010135_3	Oily fish consumption	7.000000e-17
GCST010140_3	Pork consumption	6.000000e-11
GCST010140_47	Pork consumption	7.000000e-17
GCST010142_62	Fish- and plant-related diet	4.000000e-13
GCST010142_83	Fish- and plant-related diet	4.000000e-08
GCST010142_87	Fish- and plant-related diet	2.000000e-19
GCST010142_94	Fish- and plant-related diet	5.000000e-13
GCST010244_424	Triglyceride levels	1.000000e-09
GCST012477_2	Invasive cervical cancer	3.000000e-09
GCST90013406_19	Liver enzyme levels (alkaline phosphatase)	9.000000e-28

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0008111	diet measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885507 (PROTEIN FAMILY), CHEMBL4829 (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: 3,011 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3545313	BEMPEDOIC ACID	4	787
CHEMBL3359265	PF-05175157	2	270
CHEMBL3407547	FIRSOCOSTAT	2	1,211
CHEMBL4567446	CLESACOSTAT	2	743

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Carboxylases

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 2e [PMID: 31900320]	Inhibition	8.72	pIC50
compound 21 [PMID: 23981033]	Inhibition	8.4	pIC50
firsocostat	Negative	8.21	pIC50
A-908292	Inhibition	7.64	pIC50
clesacostat	Inhibition	7.6	pIC50
CP-640186	Inhibition	7.42	pIC50
TOFA	Inhibition	4.91	pIC50

Binding affinities (BindingDB)

3267 measured of 3498 human assays (3498 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-3-((1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxa-1,4-dihydrothieno[2,3-d]pyrimidine-3(2H)-yl)methyl)cyclobutane-1-carboxylic acid	IC50	0.487 nM	US-12384798: ACC inhibitor and use thereof
(R)-2-(3-(1-(2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidine-3(2H)-yl)cyclobutyl)acetic acid	IC50	0.688 nM	US-12384798: ACC inhibitor and use thereof
2-((1R,3R)-3-(1-((R)-2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidine-3(4H)-yl)cyclobutyl)acetic acid	IC50	0.836 nM	US-12384798: ACC inhibitor and use thereof
2-((1S,3S)-3-(1-((R)-2-(2-methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(oxazol-2-yl)-2,4-dioxo-1,2-dihydrothieno[2,3-d]pyrimidine-3(4H)-yl)cyclobutyl)acetic acid	IC50	1.12 nM	US-12384798: ACC inhibitor and use thereof
N-[(2S)-1-[4-(6-cyclobutyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	2 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(7-chloro-6-cyclopropyloxy-4-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	2 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[(2-ethoxy-[1,3]thiazolo[5,4-b]pyridin-5-yl)oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[(2-ethoxy-[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]cyclohexyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-cyclopropyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-cyclopropyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]-2,2-difluoroacetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-ethoxy-5,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[6-(3,3-difluorocyclobutyl)oxy-4,7-difluoro-1-methylbenzimidazol-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(7-chloro-6-ethoxy-4-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	3 nM	US-10150728: Alkylene derivatives
2-tert-butyl-1’-[2-(cyclobutylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	3.4 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
N-[(2S)-1-[4-(6-cyclopropyloxy-7-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	3.9 nM	US-10233156: 9-membered fused ring derivative
N-[(2S)-1-[4-[[2-(cyclopropylmethoxy)-7-fluoro-1,3-benzothiazol-6-yl]oxy]cyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[[2-(3,3-difluorocyclobutyl)oxy-[1,3]thiazolo[4,5-c]pyridin-6-yl]oxy]cyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[(2-cyclopropyloxy-7-fluoro-[1,3]thiazolo[4,5-c]pyridin-6-yl)oxy]cyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[(2-cyclobutyloxy-[1,3]thiazolo[5,4-b]pyridin-5-yl)oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[5-chloro-6-[(4-chloro-2-pyridinyl)methoxy]pyrimidin-4-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[5-chloro-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[5-chloro-6-[(5-chloro-1,3-thiazol-2-yl)methoxy]pyrimidin-4-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[6-[(4-chloro-2-pyridinyl)methoxy]-5-fluoropyrimidin-4-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[5-fluoro-6-[(4-fluorophenyl)methoxy]pyrimidin-4-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-4-[4-[[5-(5-chloropyrimidin-2-yl)-3-fluoro-2-pyridinyl]oxy]cyclohexyl]butan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-4-[4-(7-chloro-6-cyclopropyloxy-1-methylimidazo[4,5-c]pyridin-2-yl)oxycyclohexyl]butan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[7-chloro-6-(2,2-difluoroethoxy)-4-fluoro-1-methylbenzimidazol-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(4-chloro-6-ethoxy-7-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[6-(2,2-difluoroethoxy)-5,7-difluoro-1-methylbenzimidazol-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-ethoxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-4-[(2R,5R)-5-[7-chloro-6-(2,2-difluoroethoxy)-4-fluoro-1-methylbenzimidazol-2-yl]oxyoxan-2-yl]butan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
[(2S)-1-[4-(6-cyclopropyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]urea	IC50	4 nM	US-10150728: Alkylene derivatives
2-cyano-N-[(2S)-1-[4-(6-cyclopropyloxy-4,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-cyclopropyloxy-4-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	4 nM	US-10150728: Alkylene derivatives
N-[(2R)-1-[4-[7-chloro-6-(2,2-difluoroethoxy)-4-fluoro-1-methylbenzimidazol-2-yl]oxycyclohexyl]oxy-3-fluoropropan-2-yl]acetamide	IC50	4.6 nM	US-10233156: 9-membered fused ring derivative
N-[(2R)-1-[4-(6-cyclopropyloxy-4-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxy-3-fluoropropan-2-yl]acetamide	IC50	4.7 nM	US-10233156: 9-membered fused ring derivative
N-[(2S)-1-[3-[(2-propan-2-yloxy-[1,3]thiazolo[5,4-b]pyridin-5-yl)oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[(2-ethoxy-6-fluoro-[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]cyclohexyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[3-[[2-[(1-methylcyclopropyl)methoxy]-[1,3]thiazolo[5,4-b]pyridin-5-yl]oxymethyl]cyclobutyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[6-(cyclopropylmethoxy)-7-fluoro-1-methylimidazo[4,5-c]pyridin-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-4-[(2R,5R)-5-[6-(2,2-difluoroethoxy)-4,7-difluoro-1-methylbenzimidazol-2-yl]oxyoxan-2-yl]butan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[7-chloro-6-(cyclopropylmethoxy)-1-methylimidazo[4,5-c]pyridin-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
[(2S)-4-[4-(7-chloro-6-cyclopropyloxy-1-methylimidazo[4,5-c]pyridin-2-yl)oxycyclohexyl]butan-2-yl]urea	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(7-chloro-6-ethoxy-4-fluoro-1-methylimidazo[4,5-c]pyridin-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-[7-chloro-6-[(2,2-difluorocyclopropyl)methoxy]-1-methylimidazo[4,5-c]pyridin-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-4-[5-[7-chloro-6-(2,2-difluoroethoxy)-4-fluoro-1-methylbenzimidazol-2-yl]oxy-1,3-dioxan-2-yl]butan-2-yl]acetamide	IC50	5 nM	US-10150728: Alkylene derivatives
N-[(2S)-1-[4-(6-cyclobutyloxy-4-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5.1 nM	US-10233156: 9-membered fused ring derivative
[(2S)-1-[4-(6-cyclopropyloxy-7-fluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]urea	IC50	5.3 nM	US-10233156: 9-membered fused ring derivative
N-[(2S)-1-[4-[6-(2,2-difluoroethoxy)-4,5,7-trifluoro-1-methylbenzimidazol-2-yl]oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5.3 nM	US-10233156: 9-membered fused ring derivative
N-[(2S)-1-[4-(6-cyclopropyloxy-5,7-difluoro-1-methylbenzimidazol-2-yl)oxycyclohexyl]oxypropan-2-yl]acetamide	IC50	5.4 nM	US-10233156: 9-membered fused ring derivative

ChEMBL bioactivities

4258 potent at pChembl≥5 of 4326 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.68	IC50	0.21	nM	CHEMBL1089882
9.52	IC50	0.3	nM	CHEMBL1089883
9.51	IC50	0.31	nM	CHEMBL1091996
9.00	IC50	1	nM	CHEMBL3699916
8.96	IC50	1.1	nM	CHEMBL2419600
8.95	IC50	1.13	nM	CHEMBL5768893
8.89	IC50	1.3	nM	CHEMBL2323626
8.82	IC50	1.5	nM	CHEMBL2419589
8.77	IC50	1.7	nM	CHEMBL2419600
8.77	IC50	1.7	nM	FIRSOCOSTAT
8.77	IC50	1.7	nM	CHEMBL2419598
8.77	IC50	1.7	nM	CHEMBL3699930
8.76	IC50	1.72	nM	CHEMBL3699929
8.75	IC50	1.76	nM	CHEMBL5788250
8.74	IC50	1.8	nM	CHEMBL3699918
8.72	IC50	1.9	nM	CHEMBL3699881
8.72	IC50	1.9	nM	CHEMBL4225405
8.70	IC50	2	nM	CHEMBL5825494
8.70	IC50	2	nM	CHEMBL6059087
8.68	IC50	2.1	nM	CHEMBL2323628
8.68	IC50	2.1	nM	CHEMBL3699871
8.68	IC50	2.1	nM	CHEMBL3699886
8.68	IC50	2.1	nM	CHEMBL3699903
8.68	IC50	2.1	nM	CHEMBL4229067
8.66	IC50	2.2	nM	CHEMBL3699914
8.66	IC50	2.19	nM	CHEMBL5918349
8.64	IC50	2.3	nM	CHEMBL2419589
8.62	IC50	2.4	nM	CHEMBL3699889
8.62	IC50	2.4	nM	CHEMBL3699893
8.62	IC50	2.4	nM	CHEMBL3699915
8.60	IC50	2.5	nM	CHEMBL3699925
8.59	IC50	2.6	nM	CHEMBL2419597
8.59	IC50	2.6	nM	CHEMBL3699913
8.59	IC50	2.6	nM	FIRSOCOSTAT
8.57	IC50	2.7	nM	CHEMBL3699873
8.57	IC50	2.7	nM	CHEMBL3699924
8.57	IC50	2.7	nM	CHEMBL3699927
8.56	IC50	2.74	nM	CHEMBL5791009
8.55	IC50	2.81	nM	CHEMBL6149358
8.54	IC50	2.9	nM	CHEMBL2323629
8.54	IC50	2.9	nM	CHEMBL3699921
8.52	IC50	3	nM	CHEMBL2419593
8.52	IC50	3	nM	CHEMBL221169
8.52	IC50	3	nM	CHEMBL4557289
8.52	Kd	3	nM	CHEMBL540678
8.52	IC50	3	nM	CHEMBL5923446
8.52	IC50	3	nM	CHEMBL5835621
8.52	IC50	3	nM	CHEMBL5744755
8.52	IC50	3	nM	CHEMBL6031375
8.52	IC50	3	nM	CHEMBL6034807

PubChem BioAssay actives

619 with measured affinity, of 742 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
6-(1-methylpyrazol-4-yl)-1’-[2-(1-methylpyrazol-3-yl)-3H-benzimidazole-5-carbonyl]spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0002	uM
1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1-methylpyrazol-4-yl)spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0003	uM
6-methoxy-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-pyrano[2,3-c]pyridine-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0003	uM
2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydroindazole-5,4’-piperidine]-7-one	725836: Inhibition of human recombinant ACC2	ic50	0.0013	uM
2-[1-[(2R)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid	1195663: In vitro inhibition of human recombinant His-tagged ACC2 assessed as malonyl-CoA level	ic50	0.0017	uM
2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0017	uM
N-[(E,2S)-4-[6-[(7-chloro-2-ethoxy-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide	1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis	ic50	0.0019	uM
N-[(E,2S)-4-[6-[(7-fluoro-2-propan-2-yl-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide	1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis	ic50	0.0021	uM
1’-(6-methoxyquinoline-3-carbonyl)-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-7-one	725836: Inhibition of human recombinant ACC2	ic50	0.0021	uM
2-tert-butyl-1’-[2-(dimethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0023	uM
5-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-1H-indole-2-carboxamide	725836: Inhibition of human recombinant ACC2	ic50	0.0029	uM
N-[(1S)-1-[3-[2-(4-propan-2-yloxyphenoxy)-1,3-thiazol-5-yl]-1,2-oxazol-5-yl]ethyl]acetamide	280225: Inhibition of human recombinant ACC2 expressed in SF9 cells	ic50	0.0030	uM
5-[1’-(1-cyclopropyl-4-methoxy-3-methylindole-6-carbonyl)-4-oxospiro[3H-chromene-2,4’-piperidine]-6-yl]pyridine-3-carboxylic acid	1546894: Inhibition of ACC2 (unknown origin)	ic50	0.0030	uM
[(1R,2S,5S,10S,11R,12E,14S,15S,16S,17S,18R)-1,17-dihydroxy-10,18-dimethoxy-2,14,16-trimethyl-3-oxo-5-phenyl-4,19-dioxabicyclo[13.3.1]nonadec-12-en-11-yl] 3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoate	426474: Binding affinity to human His-tagged acetyl-CoA-carboxylase biotin carboxylase domain	kd	0.0030	uM
2-tert-butyl-1’-(3-chloro-1H-indole-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0030	uM
N-[4-[2-(4-propoxyphenoxy)-1,3-thiazol-5-yl]but-3-yn-2-yl]acetamide	276641: Inhibition of human recombinant ACC2	ic50	0.0040	uM
2-tert-butyl-1’-(2-methoxyquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0040	uM
2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0042	uM
2-tert-butyl-1’-(1-methoxyisoquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0042	uM
N-[(E,2S)-4-[6-[(7-chloro-2-propan-2-yl-1,3-benzothiazol-6-yl)oxy]-3-pyridinyl]but-3-en-2-yl]acetamide	1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis	ic50	0.0043	uM
1-[3-[4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-9-azaspiro[4.5]decan-9-yl]piperidine-1-carbonyl]-6-methylthieno[2,3-b]pyridin-2-yl]-3-methylurea	662187: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0044	uM
1’-(7-methyl-1H-indazole-5-carbonyl)-5-propan-2-yloxyspiro[3H-pyrano[3,2-c]pyridine-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0045	uM
1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1H-pyrazol-5-yl)spiro[3H-chromene-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0045	uM
1’-(3,7-dimethyl-2H-indazole-5-carbonyl)-2-(2-methylbutan-2-yl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0045	uM
1-[3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]-3-ethylurea	672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0049	uM
N-[4-[2-[4-(cyclopentylmethoxy)phenoxy]-1,3-thiazol-5-yl]but-3-yn-2-yl]acetamide	276641: Inhibition of human recombinant ACC2	ic50	0.0050	uM
4-[6-(dimethylamino)-4-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-2-pyridinyl]benzoic acid	1675564: Inhibition of recombinant human ACC2 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay	ic50	0.0050	uM
2-tert-butyl-1’-(3-chloro-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0050	uM
1-[3-[4-(1,3-dioxospiro[5,6,7,8,9,10-hexahydropyrazolo[1,2-a]diazocine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-ethylurea	672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0051	uM
1-[3-[4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-9-azaspiro[4.5]decan-9-yl]piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-ethylurea	626469: Inhibition of human ACC2	ic50	0.0054	uM
N-[(1S)-1-[3-[(2S)-4-(4-ethoxy-2-methylphenyl)-2-methylpiperazin-1-yl]-1,2,4-oxadiazol-5-yl]ethyl]acetamide	1065780: Inhibition of human ACC2 expressed in CHOK1 cells assessed as acetylCoA to malonylCoA conversion after 1 hr by LC-MS/MS analysis	ic50	0.0054	uM
[3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]urea	672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0059	uM
N-[4-[4-(4-propan-2-yloxyphenoxy)phenyl]but-3-yn-2-yl]acetamide	267164: Inhibition of human recombinant ACC2 expressed in baculovirus/sf9 system	ic50	0.0060	uM
2-tert-butyl-1’-[1-(methylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0060	uM
2-tert-butyl-1’-(3,7-dimethyl-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0060	uM
1-[3-[4-(1,3-dioxospiro[5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-7-methoxy-1-benzothiophen-2-yl]-3-methylurea	672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0061	uM
1’-(7-methyl-1H-indazole-5-carbonyl)-6-(1-methylpyrazol-3-yl)spiro[3H-chromene-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0061	uM
6-(3,5-dimethyl-1,2-oxazol-4-yl)-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-chromene-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0064	uM
5-methoxy-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[3H-chromene-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0065	uM
2-tert-butyl-1’-(2,7-dimethyl-3H-benzimidazole-5-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	648875: Inhibition of human Acetyl-CoA carboxylase 2 expressed in CHO cells after 1 hr by fluorescence assay	ic50	0.0066	uM
2-tert-butyl-1’-(3-chloro-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0067	uM
2-tert-butyl-1’-(3-chloro-1H-indole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767839: Inhibition of human ACC2 using acetyl-CoA as substrate assessed as [14C]malonyl-CoA synthesis preincubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting analysis in presence of NaH[14C]O3	ic50	0.0068	uM
N-[(E,2S)-4-[6-[2-chloro-4-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]but-3-en-2-yl]acetamide	1393080: Inhibition of recombinant human ACC2 assessed as reduction in conversion of acetyl-CoA to malonyl-CoA incubated for 1 to 3 hrs with substrate by MALDI-TOF-MS analysis	ic50	0.0069	uM
2-tert-butyl-1’-(7-methyl-1H-indazole-5-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	648875: Inhibition of human Acetyl-CoA carboxylase 2 expressed in CHO cells after 1 hr by fluorescence assay	ic50	0.0069	uM
N-[4-[2-[4-(cyclopropylmethoxy)phenoxy]-1,3-thiazol-5-yl]but-3-yn-2-yl]acetamide	280225: Inhibition of human recombinant ACC2 expressed in SF9 cells	ic50	0.0070	uM
N-[1-[4-[4-(4-phenoxyphenoxy)phenyl]phenyl]ethyl]acetamide	445760: Inhibition of human recombinant ACC 2 expressed in baculovirus expression system by FAS-coupled assay	ic50	0.0070	uM
2-tert-butyl-1’-(7-methyl-3H-benzimidazole-5-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	648875: Inhibition of human Acetyl-CoA carboxylase 2 expressed in CHO cells after 1 hr by fluorescence assay	ic50	0.0074	uM
1-[3-[4-(1,3-dioxospiro[6,7,8,9-tetrahydro-5H-pyrazolo[1,2-a]diazepine-2,3’-piperidine]-1’-yl)piperidine-1-carbonyl]-1-benzothiophen-2-yl]-3-ethylurea	672140: Inhibition of human ACC2 using acetyl-coA as substrate incubated for 60 mins prior to substrate addition measured after 20 mins by malachite green assay	ic50	0.0075	uM
1’-(7-methyl-1H-indazole-5-carbonyl)-6-(5-methyl-1H-pyrazol-3-yl)spiro[3H-chromene-2,4’-piperidine]-4-one	476841: Inhibition of human recombinant ACC2 expressed in CHO cells after 1 hr by fluorescence reader	ic50	0.0076	uM
N-[1-[3-[2-(4-propan-2-yloxyphenoxy)-1,3-thiazol-5-yl]-1,2-oxazol-5-yl]ethyl]acetamide	280225: Inhibition of human recombinant ACC2 expressed in SF9 cells	ic50	0.0080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Acetaminophen	decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	increases expression, decreases expression	2
Dexamethasone	affects cotreatment, increases expression	2
Lead	affects methylation, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression, decreases expression, affects cotreatment	2
Valproic Acid	affects expression, affects methylation, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
beta-thujone	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
spathulenol	affects cotreatment, increases expression	1
arsenite	decreases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
linalool	affects cotreatment, increases expression	1
perfluorooctanoic acid	decreases expression	1
caryophyllene	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
AICA ribonucleotide	increases phosphorylation	1

ChEMBL screening assays

81 unique, capped per target: 81 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110301	Binding	Inhibition of human recombinant ACC1/2	(4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD