ACACA

Summary

ACACA (acetyl-CoA carboxylase alpha, HGNC:84) is a protein-coding gene on chromosome 17q12, encoding Acetyl-CoA carboxylase 1 (Q13085). Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. It is a selective cancer dependency (DepMap: 26.6% of cell lines).

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. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5’ sequence and encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 31 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acetyl-coa carboxylase deficiency (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 476 total — 3 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 26.6% of screened cell lines
• MANE Select transcript: NM_198834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:84
Approved symbol	ACACA
Name	acetyl-CoA carboxylase alpha
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	ACC1, ACC-alpha, ACCA, ACCalpha, ACACalpha, Acac1, hACC1
Ensembl gene	ENSG00000278540
Ensembl biotype	protein_coding
OMIM	200350
Entrez	31

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 10 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 1 non_stop_decay

ENST00000612007, ENST00000612120, ENST00000612895, ENST00000612926, ENST00000613146, ENST00000613776, ENST00000614333, ENST00000614428, ENST00000614438, ENST00000614450, ENST00000614482, ENST00000614789, ENST00000615229, ENST00000616317, ENST00000616352, ENST00000617548, ENST00000617649, ENST00000618053, ENST00000618351, ENST00000618575, ENST00000619245, ENST00000619546, ENST00000621960

RefSeq mRNA: 5 — MANE Select: NM_198834 NM_198834, NM_198836, NM_198837, NM_198838, NM_198839

CCDS: CCDS11317, CCDS11318, CCDS42302, CCDS42303

Canonical transcript exons

ENST00000616317 — 56 exons

Exon	Start	End
ENSE00003711809	37234975	37235099
ENSE00003712872	37121355	37121490
ENSE00003713465	37125698	37125794
ENSE00003713472	37240476	37240564
ENSE00003715963	37155683	37155780
ENSE00003717027	37257703	37257866
ENSE00003718107	37224992	37225105
ENSE00003718686	37088938	37089074
ENSE00003719856	37248011	37248156
ENSE00003720725	37283267	37283405
ENSE00003723069	37111531	37111643
ENSE00003726147	37243371	37243559
ENSE00003726892	37263685	37263894
ENSE00003728369	37181201	37181356
ENSE00003729292	37226339	37226452
ENSE00003730108	37200139	37200183
ENSE00003730337	37192090	37192305
ENSE00003730946	37221724	37221842
ENSE00003731706	37130075	37130218
ENSE00003731907	37206783	37206879
ENSE00003731966	37161781	37162050
ENSE00003732149	37277033	37277114
ENSE00003732213	37258212	37258373
ENSE00003732433	37223512	37223601
ENSE00003732440	37275951	37276049
ENSE00003732606	37210467	37210490
ENSE00003732890	37179260	37179406
ENSE00003734280	37252886	37253036
ENSE00003734814	37191120	37191275
ENSE00003735484	37193374	37193415
ENSE00003736690	37252005	37252108
ENSE00003736988	37246826	37246976
ENSE00003737982	37274193	37274299
ENSE00003738753	37129365	37129485
ENSE00003740675	37084992	37087439
ENSE00003740987	37245080	37245214
ENSE00003741169	37241953	37242053
ENSE00003741519	37207657	37207800
ENSE00003741681	37200427	37200483
ENSE00003742848	37096996	37097166
ENSE00003743039	37270751	37270861
ENSE00003743164	37248593	37248674
ENSE00003743531	37122531	37122627
ENSE00003744386	37149864	37149974
ENSE00003744996	37097830	37097984
ENSE00003745678	37113088	37113265
ENSE00003746195	37205765	37205872
ENSE00003748166	37188277	37188480
ENSE00003748405	37151301	37151421
ENSE00003748605	37330173	37330425
ENSE00003749439	37259360	37259530
ENSE00003750104	37277896	37278005
ENSE00003750795	37339804	37339850
ENSE00003752159	37244588	37244734
ENSE00003786438	37284838	37284970
ENSE00003843730	37406262	37406836

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5962 / max 196.6445, expressed in 1809 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165466	21.1174	1784
165470	2.9720	1413
165467	1.7630	873
165469	0.7297	455
165468	0.0142	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.24	gold quality
adrenal tissue	UBERON:0018303	96.11	gold quality
ganglionic eminence	UBERON:0004023	95.51	gold quality
corpus callosum	UBERON:0002336	95.35	gold quality
ventricular zone	UBERON:0003053	95.23	gold quality
superior frontal gyrus	UBERON:0002661	93.19	gold quality
right adrenal gland cortex	UBERON:0035827	92.25	gold quality
prefrontal cortex	UBERON:0000451	92.15	gold quality
right adrenal gland	UBERON:0001233	92.00	gold quality
frontal cortex	UBERON:0001870	91.97	gold quality
right frontal lobe	UBERON:0002810	91.51	gold quality
prostate gland	UBERON:0002367	91.28	gold quality
cerebral cortex	UBERON:0000956	91.06	gold quality
sural nerve	UBERON:0015488	90.97	gold quality
adrenal gland	UBERON:0002369	90.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.86	gold quality
colonic epithelium	UBERON:0000397	90.83	gold quality
anterior cingulate cortex	UBERON:0009835	90.67	gold quality
left adrenal gland	UBERON:0001234	90.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.33	gold quality
primary visual cortex	UBERON:0002436	90.29	gold quality
left adrenal gland cortex	UBERON:0035825	90.11	gold quality
esophagus mucosa	UBERON:0002469	89.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.85	gold quality
brain	UBERON:0000955	89.73	gold quality
right testis	UBERON:0004534	89.65	gold quality
temporal lobe	UBERON:0001871	89.50	gold quality
amygdala	UBERON:0001876	89.39	gold quality
esophagus	UBERON:0001043	89.28	gold quality
hypothalamus	UBERON:0001898	89.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPB, CREB1, CREBZF, FOXO1, MLXIPL, NR1H3, NR1H4, NRF1, PPARD, SP1, SREBF1, STAT3, STAT5A, THRB, USF1, USF2

miRNA regulators (miRDB)

77 targeting ACACA, 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-5193	100.00	67.26	1744
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
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-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-7159-5P	99.53	72.12	2472

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.6% of screened cell lines.

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)
• folding of the T4 major capsid protein requires a gp31-dependent cis-folding mechanism likely inside an enlarged “Anfinsen cage” provided by GroEL and gp31 (PMID:15919824)
• enlarged volume for folding is consistent with the size of the bacteriophage coat protein gp23, which is the major substrate of GroEL-gp31 chaperonin complex (PMID:16549073)
• structures of gp23-chaperonin complexes, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber (PMID:19122642)
• Human acetyl-CoA carboxylase 1 gene has three promoters and heterogeneity at the 5’-untranslated mRNA region (PMID:12810950)
• Transcription of ACC-alpha from at least three promoters and the potential to generate ACC-alpha isozymes with differential susceptibilities to phosphorylation indicate that the regulation of fatty acid synthesis in human tissues is likely to be complex (PMID:14643797)
• polymorphisms in acetyl-Coenzyme A carboxylase alpha is associated with breast cancer predisposition (PMID:15333468)
• BRCA1 affects lipogenesis through binding to P-ACCA, suggesting a new mechanism by which BRCA1 may exert a tumor suppressor function (PMID:16326698)
• the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263. (PMID:16698035)
• a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer (PMID:17372234)
• observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors (PMID:17521700)
• the major mechanism of HER2-mediated induction of FASN and ACCalpha in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway. (PMID:17631500)
• AKR1B10 regulates the stability of acetyl-CoA carboxylase-alpha and is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells (PMID:18056116)
• biochemical analysis of human BRCA1 BRCT domains in complex with a phospho-peptide from human ACC1 (PMID:18452305)
• Differential activation of recombinant ACC1 and ACC2 by citrate is reported. (PMID:18455495)
• AMPK alpha2 activity, AMPK alpha2 Thr172 phosphorylation, and ACC-beta Ser222 phosphorylation were increased immediately after exercise. These increases had all returned to basal levels at 3 and 24 h after exercise. (PMID:18614941)
• Data suggest that increased expression of malonyl CoA decarboxylase, and the decreased expression of acetyl CoA carboxylase and 5’-AMP activated protein kinase are important regulators of the maturation of fatty acid oxidation in the newborn human heart. (PMID:18614968)
• The interaction between BRCA1 and acetyl-CoA-carboxylase is regulated during cell cycle progression. (PMID:19061860)
• ACC was down-regulated in visceral adipose tissue from obese subjects, with and without diabetes mellitus type 2 (PMID:19543203)
• data suggest that cancer cells require active SCD1 to control the rate of glucose-mediated lipogenesis, and that when SCD1 activity is impaired cells downregulate SFA synthesis via AMPK-mediated inactivation of acetyl-CoA carboxylase (PMID:19710915)
• Data show that kidney bean husk extract exhibited antitumor effects accompanied by the increase in p-AMPK and p-Acc as well as antitumor proteins p53 and p21. (PMID:19723093)
• Transient over-expression of CREB1 in HepG2 cells activates ACC1 PII promoter and induces the production of triacylglycerol in response to arachidonic acid (AA), indicating that the effect of AA on ACC1 is possibly regulated via CREB1. (PMID:19842072)
• This study supports the hypothesis that the direct effects of some antipsychotics on hypertriglyceridemia may be at least partially mediated by the ACACA gene. (PMID:19846279)
• data suggest that insulin and glucocorticoid have positive effects on both acetyl-CoA carboxylase alpha(ACC1) and beta(ACC2) gene transcription (PMID:20139635)
• show that MIG12, a 22 kDa cytosolic protein of previously unknown function, binds to ACC and lowers the threshold for citrate activation into the physiological range. (PMID:20457939)
• Human cytomegalovirus infection induces an increase in ACC1 mRNA and protein expression. (PMID:21471234)
• IGF-1 reduced ACCalpha phosphorylation via an ATM/AMPK signaling pathway and suppressed ACCalpha expression through an ERK1/2 (PMID:21638027)
• three major enzymes of the pathway, FASN, ACC, and ACLY, are up-regulated in numerous tumor types. (PMID:21726077)
• Metabolic regulation of invadopodia and invasion by acetyl-CoA carboxylase 1 and de novo lipogenesis. (PMID:22238651)
• Exercise training increased AMPKalpha1 activity in older men, however, AMPKalpha2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected (PMID:23000302)
• Single nucleotide polymorphisms in the ACACA and ACLY genes are associated with a relative change in plasma triglycierides following fish oil supplementation. (PMID:23886516)
• Phospho-acetyl-CoA carboxylase protein expression correlates with tumor grade and the disease stage in gastric cancer. (PMID:24924473)
• ACAT1, ACACA, ALDH6A1 and MTHFD1 represent novel biomarkers in adipose tissue associated with type 2 diabetes in obese individuals. (PMID:25099943)
• ACACA may constitute a previously unrecognized target for novel anti-breast cancer stem cell therapies. (PMID:25246709)
• 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)
• 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)
• acetyl-CoA carboxylase 1 and senescence regulation in human fibroblasts involves oxidant mediated p38 MAPK activation (PMID:27983949)
• Inhibition of Acetyl-CoA Carboxylase 1 (ACC1) and 2 (ACC2) Reduces Proliferation and De Novo Lipogenesis of EGFRvIII Human Glioblastoma Cells (PMID:28081256)
• These data showed that ACC1 gene (ACACA) expression was twofold greater in HCC compared to non-cancerous liver. (PMID:28290443)
• of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. (PMID:28768177)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acaca	ENSDARG00000078512
		ENSDARG00000113739
mus_musculus	Acaca	ENSMUSG00000020532
rattus_norvegicus	Acaca	ENSRNOG00000034013

Paralogs (4): ACACB (ENSG00000076555), MCCC1 (ENSG00000078070), PC (ENSG00000173599), PCCA (ENSG00000175198)

Protein

Protein identifiers

Acetyl-CoA carboxylase 1 — Q13085 (reviewed: Q13085)

Alternative names: Acetyl-Coenzyme A carboxylase alpha

All UniProt accessions (10): Q13085, A0A087WVR6, A0A087WWN5, A0A087WYK6, A0A087WYS8, A0A087X0W4, A0A087X126, A0A087X2F8, A0A0C4DGT1, Q59FY4

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. This is 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.

Subunit / interactions. Monomer, homodimer, and homotetramer. Can form filamentous polymers. Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in brain, placenta, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver.

Post-translational modifications. Phosphorylation on Ser-1263 is required for interaction with BRCA1. Phosphorylation at Ser-80 by AMPK inactivates enzyme activity. The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.

Disease relevance. Acetyl-CoA carboxylase-alpha deficiency (ACACAD) [MIM:613933] An autosomal recessive inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by phosphorylation. Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase. Inhibited by palmitoyl-CoA.

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 (4)

UniProt ID	Names	Canonical?
Q13085-1	1	yes
Q13085-2	2, E5A
Q13085-3	3, E5B
Q13085-4	4

RefSeq proteins (5): NP_942131, NP_942133, NP_942134, NP_942135, NP_942136 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000089	Biotin_lipoyl	Domain
IPR001882	Biotin_BS	Binding_site
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 6.4.1.2 — acetyl-CoA carboxylase (BRENDA: 88 organisms, 133 substrates, 705 inhibitors, 131 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–1.2	39
ATP	0.015–0.5	38
HCO3-	0.3–12.8	27
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
ACETODETHIO-COA	1.25	1
MG2+	0.83	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (288 total): helix 86, strand 84, sequence conflict 38, modified residue 25, turn 21, binding site 12, mutagenesis site 8, domain 5, splice variant 3, sequence variant 3, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2YL2	X-RAY DIFFRACTION	2.3
8XKZ	ELECTRON MICROSCOPY	2.55
8XL1	ELECTRON MICROSCOPY	2.57
8XL2	ELECTRON MICROSCOPY	2.73
4ASI	X-RAY DIFFRACTION	2.8
3COJ	X-RAY DIFFRACTION	3.21
8XL0	ELECTRON MICROSCOPY	4.14
6G2H	ELECTRON MICROSCOPY	4.6
6G2D	ELECTRON MICROSCOPY	5.4
6G2I	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13085-F1	83.05	0.41

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): 441

Ligand- & substrate-binding residues (12): 424; 437; 437; 437; 437; 439; 439; 1823; 2127; 2129; 315–320; 424

Post-translational modifications (25): 1, 5, 23, 25, 29, 34, 48, 50, 53, 58, 78, 80, 488, 610, 786, 835, 1201, 1216, 1218, 1227 …

Mutagenesis-validated functional residues (8):

Position	Phenotype
78	no effect on interaction with brca1.
344	no effect on interaction with brca1.
432	no effect on interaction with brca1.
1201	no effect on interaction with brca1.
1263	abolishes interaction with brca1.
1585	no effect on interaction with brca1.
1952	no effect on interaction with brca1.
2211	no effect on interaction with brca1.

Function

Pathways and Gene Ontology

Reactome pathways

18 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-3371599	Defective HLCS causes multiple carboxylase deficiency
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-1430728	Metabolism
R-HSA-163685	Integration of energy metabolism
R-HSA-1643685	Disease
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-3296482	Defects in vitamin and cofactor metabolism
R-HSA-3323169	Defects in biotin (Btn) metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-5668914	Diseases of metabolism
R-HSA-8957322	Metabolism of steroids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 360 (showing top): GGGACCA_MIR133A_MIR133B, YAATNRNNNYNATT_UNKNOWN, HNF3ALPHA_Q6, GOBP_PROTEIN_HOMOTETRAMERIZATION, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_CELLULAR_RESPONSE_TO_LIPID, AAGTCCA_MIR422B_MIR422A, TTTGTAG_MIR520D, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, ACTGCAG_MIR173P, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (12): tissue homeostasis (GO:0001894), acetyl-CoA metabolic process (GO:0006084), fatty acid biosynthetic process (GO:0006633), fatty-acyl-CoA biosynthetic process (GO:0046949), protein homotetramerization (GO:0051289), lipid homeostasis (GO:0055088), cellular response to prostaglandin E stimulus (GO:0071380), malonyl-CoA biosynthetic process (GO:2001295), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), acyl-CoA metabolic process (GO:0006637), lipid biosynthetic process (GO:0008610)

GO Molecular Function (8): acetyl-CoA carboxylase activity (GO:0003989), ATP binding (GO:0005524), 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): fibrillar center (GO:0001650), mitochondrion (GO:0005739), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Metabolism	3
Fatty acid metabolism	2
Metabolism of lipids	2
Integration of energy metabolism	1
Metabolism of water-soluble vitamins and cofactors	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Defects in biotin (Btn) metabolism	1
Metabolism of steroids	1
Metabolism of vitamins and cofactors	1
Diseases of metabolism	1
Defects in vitamin and cofactor metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
acyl-CoA biosynthetic process	2
lipid metabolic process	2
cytoplasm	2
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
acyl-CoA metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
fatty-acyl-CoA metabolic process	1
fatty acid derivative biosynthetic process	1
protein homooligomerization	1
protein tetramerization	1
chemical homeostasis	1
response to prostaglandin E	1
cellular response to prostaglandin stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
malonyl-CoA metabolic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
nucleoside phosphate metabolic process	1
sulfur compound metabolic process	1
purine-containing compound metabolic process	1
biosynthetic process	1
CoA carboxylase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
catalytic activity	1
nucleolus	1
intracellular membrane-bounded organelle	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACACA	FASN	P49327	965
ACACA	SREBF1	P36956	928
ACACA	ACLY	P53396	900
ACACA	SCD	O00767	893
ACACA	CPT1A	P50416	848
ACACA	HLCS	P50747	821
ACACA	ELOVL6	Q9H5J4	813
ACACA	LEP	P41159	812
ACACA	ACSL1	P33121	793
ACACA	HMGCR	P04035	762
ACACA	MLXIPL	Q9NP71	748
ACACA	ACSL3	O95573	748
ACACA	DGAT1	O75907	738
ACACA	DGAT2	Q96PD7	731
ACACA	ADIPOQ	Q15848	725

IntAct

124 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
Mid1ip1	ACACA	psi-mi:“MI:0407”(direct interaction)	0.640
OPG200	IKBKB	psi-mi:“MI:0914”(association)	0.620
SIRT1	ACACA	psi-mi:“MI:0915”(physical association)	0.590
ACACA	SIRT1	psi-mi:“MI:0915”(physical association)	0.590
ACACA	AKR1B10	psi-mi:“MI:0915”(physical association)	0.560
AKR1B10	ACACA	psi-mi:“MI:0915”(physical association)	0.560
AKR1B10	ACACA	psi-mi:“MI:0403”(colocalization)	0.560
ACACA	ACACA	psi-mi:“MI:0407”(direct interaction)	0.560
EGLN3	ACACA	psi-mi:“MI:0914”(association)	0.530
MID1IP1	ACACB	psi-mi:“MI:0914”(association)	0.530
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
RPS6KA1	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
BRCA1	ACACA	psi-mi:“MI:0915”(physical association)	0.520
ACACA	PIN1	psi-mi:“MI:0403”(colocalization)	0.460

BioGRID (557): ACACA (Biochemical Activity), ACACA (Biochemical Activity), ACACA (Biochemical Activity), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-RNA), ACACA (Affinity Capture-RNA), ACACA (Affinity Capture-RNA), ACACA (Affinity Capture-RNA), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS), ACACA (Affinity Capture-MS)

ESM2 similar proteins: A0A286ZK88, A1L1L6, A7MB28, A8WGF4, B8BJ39, D0G6S1, O00399, O54956, P11029, P11497, Q13085, Q148G7, Q28007, Q28943, Q28DR7, Q2HJF8, Q2RAK2, Q4R4U1, Q502J7, Q5FVD6, Q5R559, Q5R5F8, Q5R7D8, Q5R8Q7, Q5SWU9, Q5ZIT8, Q5ZM73, Q6AYR2, Q6NVC5, Q6NWV3, Q6P1X5, Q6PC62, Q7TPD1, Q7TSL3, Q86XK2, Q8BG51, Q8BH44, Q8C176, Q8CHR6, Q8IWZ6

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

18 interactions.

A	Effect	B	Mechanism
AMPK	down-regulates	ACACA	phosphorylation
ACACA	down-regulates	“Food intake”
citrate(3-)	“up-regulates activity”	ACACA	binding
ACACA	“down-regulates quantity”	acetyl-CoA	“chemical modification”
ACACA	“up-regulates quantity”	malonyl-CoA	“chemical modification”
AMPK	“down-regulates activity”	ACACA	phosphorylation
PPP4C	“up-regulates activity”	ACACA	dephosphorylation
SREBF1	“up-regulates quantity by expression”	ACACA	“transcriptional regulation”
COP1	“down-regulates quantity by destabilization”	ACACA	ubiquitination
TRIB3	“down-regulates quantity by destabilization”	ACACA	binding
PRKAA2	down-regulates	ACACA	phosphorylation
MLXIPL	“up-regulates quantity by expression”	ACACA	“transcriptional regulation”
PRKAA1	“down-regulates activity”	ACACA	phosphorylation
CSNK2A1	unknown	ACACA	phosphorylation
CSNK2A2	unknown	ACACA	phosphorylation
MID1IP1	“up-regulates activity”	ACACA	binding
BRCA1	“down-regulates activity”	ACACA	binding
PRKACA	“down-regulates activity”	ACACA	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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
positive regulation of canonical Wnt signaling pathway	9	12.8×	2e-05
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	11.6×	3e-03
protein autophosphorylation	8	10.7×	3e-04
positive regulation of cell growth	6	10.1×	5e-03
Wnt signaling pathway	9	8.2×	4e-04
protein phosphorylation	13	8.1×	8e-06
negative regulation of gene expression	9	5.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	221
Likely benign	152
Benign	41

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
160879	GRCh38/hg38 17q12(chr17:36357258-37889296)x3	Pathogenic
2443957	NM_198834.3(ACACA):c.4969G>A (p.Ala1657Thr)	Pathogenic
929346	GRCh37/hg19 17q12(chr17:34815551-36244358)x3	Pathogenic

SpliceAI

9708 predictions. Top by Δscore:

Variant	Effect	Δscore
17:37087435:CCAAG:C	acceptor_gain	1.0000
17:37087436:CAAGC:C	acceptor_gain	1.0000
17:37088932:TCTCA:T	donor_loss	1.0000
17:37088933:CTCA:C	donor_loss	1.0000
17:37088934:TCA:T	donor_loss	1.0000
17:37088935:CACC:C	donor_loss	1.0000
17:37088936:ACCT:A	donor_loss	1.0000
17:37088937:CCTGC:C	donor_loss	1.0000
17:37096993:TA:T	donor_loss	1.0000
17:37096994:A:AC	donor_gain	1.0000
17:37096994:A:AG	donor_loss	1.0000
17:37096995:C:CC	donor_gain	1.0000
17:37097162:ATATC:A	acceptor_gain	1.0000
17:37097163:TATC:T	acceptor_gain	1.0000
17:37097164:ATC:A	acceptor_gain	1.0000
17:37097164:ATCC:A	acceptor_loss	1.0000
17:37097165:TC:T	acceptor_gain	1.0000
17:37097165:TCCTA:T	acceptor_loss	1.0000
17:37097166:CC:C	acceptor_gain	1.0000
17:37097166:CCTA:C	acceptor_loss	1.0000
17:37097167:C:CC	acceptor_gain	1.0000
17:37097168:T:A	acceptor_loss	1.0000
17:37097170:CA:C	acceptor_gain	1.0000
17:37097171:A:C	acceptor_gain	1.0000
17:37097824:ACTT:A	donor_loss	1.0000
17:37097826:TTA:T	donor_loss	1.0000
17:37097828:A:AC	donor_gain	1.0000
17:37097828:ACG:A	donor_gain	1.0000
17:37097828:ACGCT:A	donor_loss	1.0000
17:37097829:C:CA	donor_gain	1.0000

AlphaMissense

15734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:37155761:A:G	L1753P	1.000
17:37181262:C:A	R1587M	1.000
17:37181262:C:G	R1587T	1.000
17:37181326:C:G	G1566R	1.000
17:37181326:C:T	G1566R	1.000
17:37188419:A:T	V1508D	1.000
17:37188434:A:G	L1503P	1.000
17:37191168:G:C	N1471K	1.000
17:37191168:G:T	N1471K	1.000
17:37191224:C:G	A1453P	1.000
17:37192136:C:A	R1420M	1.000
17:37192258:G:C	F1379L	1.000
17:37192258:G:T	F1379L	1.000
17:37192260:A:G	F1379L	1.000
17:37192262:G:T	A1378D	1.000
17:37192268:G:T	A1376D	1.000
17:37192271:G:T	P1375H	1.000
17:37192277:A:G	L1373P	1.000
17:37192283:C:G	R1371P	1.000
17:37193393:G:T	T1357K	1.000
17:37200446:G:A	T1328I	1.000
17:37200452:C:G	R1326P	1.000
17:37200453:G:T	R1326S	1.000
17:37205844:A:G	L1289P	1.000
17:37205847:A:T	I1288N	1.000
17:37207696:C:T	G1234D	1.000
17:37207697:C:G	G1234R	1.000
17:37221732:A:C	H1188Q	1.000
17:37221732:A:T	H1188Q	1.000
17:37221745:A:T	L1184Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000007726 (17:37369849 G>C), RS1000042383 (17:37267764 C>G,T), RS1000054688 (17:37385952 C>A,T), RS1000065177 (17:37172565 A>G), RS1000065767 (17:37239779 T>A), RS1000082053 (17:37338595 G>A), RS1000116112 (17:37096183 AGTG>A), RS1000118931 (17:37382590 G>A), RS1000124810 (17:37247379 T>C), RS1000136863 (17:37158647 C>A), RS1000138900 (17:37266723 C>A,T), RS1000157200 (17:37232543 G>A), RS1000163324 (17:37405028 A>C), RS1000176942 (17:37376835 A>G,T), RS1000184501 (17:37396013 T>A)

Disease associations

OMIM: gene MIM:200350 | disease phenotypes: MIM:613933, MIM:616025, MIM:616789

GenCC curated gene-disease

Disease	Classification	Inheritance
acetyl-coa carboxylase deficiency	Moderate	Autosomal recessive

Mondo (4): acetyl-coa carboxylase deficiency (MONDO:0013493), hyperphosphatasia with intellectual disability syndrome 5 (MONDO:0014457), cardiac anomalies - developmental delay - facial dysmorphism syndrome (MONDO:0014773), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (3): Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262), Developmental delay-facial dysmorphism syndrome due to MED13L deficiency (Orphanet:369891), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001510	Growth delay
HP:0002151	Increased circulating lactate concentration
HP:0003198	Myopathy
HP:6000430	Reduced tissue acetyl-CoA carboxylase activity

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001941_16	Ovarian cancer	8.000000e-10
GCST011494_73	Daytime nap	5.000000e-22

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C562678	Acetyl-Coa Carboxylase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3351 (SINGLE PROTEIN), CHEMBL3885507 (PROTEIN FAMILY)

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
firsocostat	Negative	8.68	pIC50
compound 21 [PMID: 23981033]	Inhibition	8.0	pIC50
clesacostat	Inhibition	7.91	pIC50
CP-640186	Inhibition	6.39	pIC50
TOFA	Inhibition	4.91	pIC50

Binding affinities (BindingDB)

145 measured of 147 human assays (147 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[1-[(2R)-2-[[(3aR,6aS)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid	IC50	0.23 nM	US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine
(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-[1-[(2R)-2-[[(3aS,6aS)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid	IC50	1.09 nM	US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine
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
2-[1-[(2R)-2-[[(3aR,6aR)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]furan-5-yl]oxy]-2-(2-methoxyphenyl)ethyl]-5-methyl-6-oxazol-2-yl-2,4-dioxo-thieno[2,3-d]pyrimidin-3-yl]-2-methyl-propionic acid	IC50	1.42 nM	US-12428432: Thienopyrimidine derivatives having stereo configurations and use thereof in medicine
3-[1-(1H-imidazole-2-carbonyl)azetidin-3-yl]-1-[2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-4a,7a-dihydrothieno[2,3-d]pyrimidine-2,4-dione	IC50	1.69 nM	US-11186587: Compound as ACC inhibitor and use thereof
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
2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	5.6 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	5.6 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(8-methoxynaphthalene-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	5.8 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(propan-2-ylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	6.1 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(2,2,2-trifluoroethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	6.5 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(3,7-dimethyl-3a,7a-dihydro-1H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	6.6 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(4-methoxy-7-methyl-1H-indole-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	7.4 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(dimethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	7.4 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(cyclopropylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	7.5 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(3-chloro-7-methyl-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	8.4 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(7-methoxynaphthalene-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	8.5 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(ethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	8.9 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(2,2-difluoropropylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	9 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(1-methoxyisoquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	14 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(4,8-dimethoxyquinoline-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	15 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-[ethyl(methyl)amino]quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	15 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(4-methoxy-1H-indazole-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	17 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(7-methoxy-3-methyl-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	17 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(cyclobutylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	17 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(ethylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	17 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(5-methoxyquinoline-3-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	18 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(3-chloro-1H-indole-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	18 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
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	IC50	19 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(propan-2-ylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	20 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(2-methoxyquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	20 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
1’-(3,7-dimethyl-3a,7a-dihydro-1H-indazole-5-carbonyl)-2-(2-hydroxy-2-methylpropyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	21 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
5-(2-tert-butyl-7-oxospiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-1’-carbonyl)-1H-indazole-3-carboxamide	IC50	21 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(methylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	21 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(7-methoxy-1H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	23 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(3-chloro-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	23 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(propylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	24 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
1’-(3,7-dimethyl-2H-indazole-5-carbonyl)-1-propan-2-ylspiro[4,6-dihydropyrazolo[5,4-c]pyridine-5,4’-piperidine]-7-one	IC50	24.2 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(7-methyl-3a,7a-dihydro-1H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	26 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
1-tert-butyl-1’-(3,7-dimethyl-2H-indazole-5-carbonyl)spiro[4,6-dihydropyrazolo[5,4-c]pyridine-5,4’-piperidine]-7-one	IC50	27 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[2-(2-methoxyethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	27 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(3-chloro-1H-indole-5-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	27 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
1’-(2-aminoquinoline-7-carbonyl)-2-tert-butylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	28 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
1’-(3,7-dimethyl-3a,7a-dihydro-1H-indazole-5-carbonyl)-2-propan-2-ylspiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	29 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-[1-(cyclopropylamino)isoquinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	29 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(6-methoxyquinoline-3-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	30 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors
2-tert-butyl-1’-(5-methoxynaphthalene-2-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	IC50	30 nM	US-8993586: N1/N2-lactam acetyl-CoA carboxylase inhibitors

ChEMBL bioactivities

782 potent at pChembl≥5 of 802 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	IC50	0.22	nM	CHEMBL6171288
9.52	EC50	0.3	nM	CHEMBL4875701
9.49	IC50	0.32	nM	CHEMBL6161060
9.48	IC50	0.33	nM	CHEMBL6149358
9.43	IC50	0.37	nM	CHEMBL6012286
9.33	IC50	0.47	nM	CHEMBL5918349
9.31	IC50	0.49	nM	FIRSOCOSTAT
9.30	IC50	0.5	nM	FIRSOCOSTAT
9.28	IC50	0.52	nM	CHEMBL6146650
9.24	IC50	0.58	nM	CHEMBL4073202
9.20	IC50	0.63	nM	CHEMBL5923261
9.17	IC50	0.67	nM	CHEMBL5768893
9.17	IC50	0.68	nM	CHEMBL5814783
9.16	IC50	0.69	nM	CHEMBL5840411
9.15	IC50	0.7	nM	CHEMBL5986273
9.15	IC50	0.71	nM	CHEMBL6164037
9.14	IC50	0.73	nM	CHEMBL5814783
9.12	IC50	0.76	nM	CHEMBL4060253
9.10	IC50	0.79	nM	CHEMBL6174786
9.09	IC50	0.81	nM	CHEMBL5788250
9.07	IC50	0.85	nM	CHEMBL6143782
9.06	IC50	0.88	nM	CHEMBL5963413
9.06	IC50	0.87	nM	CHEMBL5991352
9.05	EC50	0.9	nM	CHEMBL4874989
9.05	IC50	0.9	nM	CHEMBL5404551
9.05	IC50	0.89	nM	CHEMBL5900123
9.04	IC50	0.91	nM	CHEMBL5856218
9.03	IC50	0.93	nM	CHEMBL5769140
9.02	IC50	0.96	nM	CHEMBL4085633
9.02	IC50	0.96	nM	CHEMBL4086127
9.02	IC50	0.95	nM	CHEMBL6168887
9.00	EC50	1	nM	CHEMBL4864719
9.00	EC50	1	nM	CHEMBL4875627
9.00	EC50	1	nM	CHEMBL4859704
9.00	EC50	1	nM	CHEMBL4861716
9.00	IC50	1	nM	CHEMBL5997686
8.98	IC50	1.05	nM	CHEMBL6173125
8.96	IC50	1.1	nM	CHEMBL6166957
8.95	IC50	1.12	nM	CHEMBL5922268
8.92	IC50	1.21	nM	CHEMBL5791009
8.91	IC50	1.22	nM	CHEMBL5926678
8.89	IC50	1.29	nM	CHEMBL4777068
8.89	IC50	1.3	nM	CHEMBL5435853
8.89	IC50	1.3	nM	CHEMBL5411569
8.87	IC50	1.35	nM	CHEMBL6057395
8.86	IC50	1.37	nM	CHEMBL5997686
8.85	IC50	1.43	nM	CHEMBL5889718
8.85	IC50	1.43	nM	CHEMBL5890205
8.85	IC50	1.43	nM	CHEMBL5757590
8.83	IC50	1.48	nM	CHEMBL6039150

PubChem BioAssay actives

465 with measured affinity, of 716 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[1-[(2R)-2-(5-fluoro-2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0003	uM
[(2S)-1-[[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]urea	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0006	uM
N-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]acetamide	1472481: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis	ic50	0.0008	uM
1-[1-[(2R)-2-[2-(difluoromethoxy)-5-fluorophenyl]-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylcyclopropane-1-carboxamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0009	uM
4-[4-(2-tert-butyl-4-oxospiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-1’-carbonyl)-6-(dimethylamino)-2-pyridinyl]benzamide	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0009	uM
N-[(2S)-1-[[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0010	uM
N-[(2S)-1-[[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0010	uM
(2R)-2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylpropanamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0010	uM
2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0010	uM
1-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-N-(1-methylcyclopropyl)sulfonylcyclopropane-1-carboxamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0010	uM
2-[1-[(2R)-2-(2-methoxyphenyl)-2-[[(1S,5R)-8-oxabicyclo[3.2.1]octan-3-yl]oxy]ethyl]-5-methyl-2,4-dioxo-6-(triazol-2-yl)thieno[2,3-d]pyrimidin-3-yl]-2-methyl-N-(1-methylcyclopropyl)sulfonylpropanamide	1760081: Inhibition of ACC1 in human HepG2 cells assessed as lipid content using 13C-labelled acetate as substrate incubated for 1 hr followed by substrate addition and measured after 24 hrs by QTOF mass spectrometer	ec50	0.0010	uM
1’-[2-(4-aminophenyl)quinoline-4-carbonyl]-2-tert-butylspiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0013	uM
2-tert-butyl-1’-(4-chloro-5-methyl-1H-indazole-7-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0013	uM
2-tert-butyl-1’-(4-chloro-5-methoxy-1H-indole-7-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0013	uM
1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethylurea	1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry	ic50	0.0015	uM
2-tert-butyl-1’-[5-methoxy-2-(methylamino)quinoline-7-carbonyl]spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0015	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	1546893: Inhibition of ACC1 (unknown origin)	ic50	0.0017	uM
2-tert-butyl-1’-[8-methyl-2-(methylamino)quinoline-3-carbonyl]spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0018	uM
2-tert-butyl-1’-[2-(propylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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	0.0018	uM
3-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]-1,1-dimethylurea	1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry	ic50	0.0021	uM
N-[1-[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-benzoxazol-6-yl]ethyl]acetamide	1472481: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis	ic50	0.0022	uM
2-tert-butyl-1’-[2-(4-methylphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0022	uM
2-tert-butyl-1’-(7-ethoxy-1,3-dimethylindazole-5-carbonyl)spiro[5,7-dihydro-1,3-benzothiazole-6,4’-piperidine]-4-one	1985719: Inhibition of full length human recombinant ACC1 expressed in baculovirus infected Sf9 cells incubated for 18 hrs in presence of ATP by envision fluorescence reader analysis	ic50	0.0022	uM
2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydroindazole-5,4’-piperidine]-7-one	725837: Inhibition of human recombinant ACC1	ic50	0.0022	uM
2-tert-butyl-1’-[2-[4-(dimethylamino)phenyl]quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0027	uM
5-[1’-(1-cyclopropyl-4-methoxy-3-methylindole-6-carbonyl)-4-oxospiro[3H-chromene-2,4’-piperidine]-6-yl]pyridine-3-carboxylic acid	1546893: Inhibition of ACC1 (unknown origin)	ic50	0.0030	uM
2-tert-butyl-1’-[2-(4-methoxyphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0032	uM
2-tert-butyl-1’-[2-(3,4-dimethoxyphenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0036	uM
1-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]-3-methylurea	1611142: Inhibition of recombinant human His-tagged ACC1 expressed in baculovirus infected SF9 cells using acetyl-CoA as substrate incubated for 60 mins followed by substrate addition and measured after 30 mins Rapidfire-Mass spectrometry	ic50	0.0038	uM
N-[4-[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1,3-oxazol-5-yl]butan-2-yl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0049	uM
2-tert-butyl-1’-[2-(dimethylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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’-(6-methoxyquinoline-3-carbonyl)-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-7-one	725837: Inhibition of human recombinant ACC1	ic50	0.0050	uM
1’-[2-(4-bromophenyl)quinoline-4-carbonyl]-2-tert-butylspiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0057	uM
N-[(2S)-1-[[2-[5-[3-(cyclopropylmethoxy)phenoxy]-2-pyridinyl]-1,3-oxazol-5-yl]oxy]propan-2-yl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0058	uM
2-tert-butyl-1’-(2-phenylquinoline-4-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0060	uM
2-tert-butyl-1’-[2-(methylamino)quinoline-7-carbonyl]spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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’-[2-(4-chlorophenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0061	uM
2-tert-butyl-1’-(3-chloro-1H-indole-6-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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	0.0070	uM
N-[1-[2-[5-[3-(cyclopropylmethoxy)phenoxy]-2-pyridinyl]-1,3-benzoxazol-6-yl]ethyl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0071	uM
N-[1-[2-[6-[3-(cyclopropylmethoxy)phenoxy]-3-pyridinyl]-1,3-benzothiazol-5-yl]ethyl]acetamide	1472479: Inhibition of recombinant human ACC1 expressed in SF-9 cells preincubated for 60 mins followed by addition of substrate solution containing acetyl-CoA after 30 mins by measuring malonyl 13C3-CoA by RapidFire mass spectrometry	ic50	0.0074	uM
4-[6-(dimethylamino)-4-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-2-pyridinyl]benzoic acid	1675565: Inhibition of recombinant human ACC1 using acetyl coA as substrate incubated for 1 hr by transcreener fluorescence polarization assay	ic50	0.0077	uM
1-[4-[4-[4-[2-[2-[(dimethylamino)methyl]-3-methyl-1H-indol-5-yl]-6-phenylpyridine-4-carbonyl]piperazin-1-yl]piperidine-1-carbonyl]piperidin-1-yl]ethanone	491135: Inhibition of human ACC1/2-mediated malonyl-CoA synthesis	ic50	0.0084	uM
2-tert-butyl-1’-[2-(4-fluorophenyl)quinoline-4-carbonyl]spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0094	uM
5-[4-[4-[1-(1-acetylpiperidine-4-carbonyl)piperidin-4-yl]piperazine-1-carbonyl]-6-phenyl-2-pyridinyl]-2-methyl-1H-indole-3-carbonitrile	491135: Inhibition of human ACC1/2-mediated malonyl-CoA synthesis	ic50	0.0097	uM
2-tert-butyl-1’-(2-methoxyquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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	0.0100	uM
N-[1-[2-[4-[3-(cyclopropylmethoxy)phenoxy]phenyl]-1-benzothiophen-5-yl]ethyl]acetamide	1472481: Inhibition of ACC1 in human HCT116 cells assessed as reduction of [14C]acetate uptake preincubated for 60 mins followed by addition of [14C]acetate and measured after 2 hrs by scintillation counting analysis	ic50	0.0110	uM
5-(7-oxo-1-propan-2-ylspiro[4,6-dihydroindazole-5,4’-piperidine]-1’-carbonyl)-1H-indole-2-carboxamide	725837: Inhibition of human recombinant ACC1	ic50	0.0110	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	767840: Inhibition of human ACC1 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	0.0110	uM
2-tert-butyl-1’-(1-methoxyisoquinoline-7-carbonyl)spiro[4,6-dihydropyrazolo[3,4-c]pyridine-5,4’-piperidine]-7-one	767840: Inhibition of human ACC1 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	0.0110	uM
2-tert-butyl-1’-(2-pyridin-4-ylquinoline-4-carbonyl)spiro[6H-pyrano[3,2-c]pyrazole-5,4’-piperidine]-7-one	1729093: Inhibition of recombinant human C-terminal His-tagged ACC1 (1 to 2383 residues) expressed in baculovirus infected Sf9 insect cells preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP-glo luminescence assay	ic50	0.0113	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
dorsomorphin	decreases phosphorylation, affects cotreatment, decreases reaction, increases phosphorylation, increases expression (+1 more)	9
bisphenol A	increases expression, decreases expression, decreases reaction	7
Resveratrol	decreases activity, decreases reaction, increases phosphorylation, affects cotreatment, increases expression (+1 more)	7
Valproic Acid	decreases expression, affects reaction, increases expression, affects expression, affects methylation	7
T0901317	decreases reaction, increases expression, decreases phosphorylation, decreases expression	6
Benzo(a)pyrene	affects methylation, affects cotreatment, decreases expression	5
Oleic Acid	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment	5
Palmitic Acid	decreases reaction, increases expression, affects cotreatment, decreases expression, decreases phosphorylation	5
AICA ribonucleotide	increases expression, increases phosphorylation	4
Cisplatin	affects expression, decreases expression	4
Glucose	increases reaction, increases phosphorylation, decreases expression, decreases phosphorylation, affects cotreatment (+2 more)	4
Metformin	decreases reaction, increases phosphorylation, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance, increases expression	3
Plant Extracts	affects cotreatment, increases expression, increases phosphorylation	3
Cyclosporine	decreases expression	3
Cadmium Chloride	decreases expression, decreases phosphorylation, increases abundance, increases expression	3
nuciferine	increases expression, decreases reaction	2
arsenite	affects binding, decreases reaction, increases reaction, increases methylation	2
mono-(2-ethylhexyl)phthalate	affects expression, decreases expression	2
perfluorooctanoic acid	decreases phosphorylation, increases expression, decreases expression	2
caryophyllene	decreases reaction, increases phosphorylation, affects cotreatment, decreases expression, affects reaction	2
cordycepin	decreases expression	2
6,8-diallyl 5,7-dihydroxy 2-(2-allyl 3-hydroxy 4-methoxyphenyl)1-H benzo(b)pyran-4-one	increases phosphorylation, decreases reaction, increases reaction, decreases activity	2
STO 609	decreases reaction, increases phosphorylation	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	2
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases expression, increases expression	2
fatostatin	decreases phosphorylation, increases reaction, decreases expression, increases response to substance	2
bisphenol AF	increases expression	2
Sunitinib	decreases phosphorylation, increases expression	2

ChEMBL screening assays

71 unique, capped per target: 71 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1048878	Binding	Inhibition of human recombinant ACC 1 expressed in baculovirus expression system by FAS-coupled assay	Potent biphenyl- and 3-phenyl pyridine-based inhibitors of acetyl-CoA carboxylase. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1V2	Abcam A-549 ACACA KO	Cancer cell line	Male
CVCL_D1ZQ	Abcam HCT 116 ACACA KO	Cancer cell line	Male
CVCL_D9X5	Ubigene HeLa ACACA KO	Cancer cell line	Female
CVCL_SB13	HAP1 ACACA (-) 1	Cancer cell line	Male
CVCL_SB14	HAP1 ACACA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome