ACMSD

Summary

ACMSD (aminocarboxymuconate semialdehyde decarboxylase, HGNC:19288) is a protein-coding gene on chromosome 2q21.3, encoding 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (Q8TDX5). Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS).

The neuronal excitotoxin quinolinate is an intermediate in the de novo synthesis pathway of NAD from tryptophan, and has been implicated in the pathogenesis of several neurodegenerative disorders. Quinolinate is derived from alpha-amino-beta-carboxy-muconate-epsilon-semialdehyde (ACMS). ACMSD (ACMS decarboxylase; EC 4.1.1.45) can divert ACMS to a benign catabolite and thus prevent the accumulation of quinolinate from ACMS.

Source: NCBI Gene 130013 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 70 total — 5 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_138326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19288
Approved symbol	ACMSD
Name	aminocarboxymuconate semialdehyde decarboxylase
Location	2q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153086
Ensembl biotype	protein_coding
OMIM	608889
Entrez	130013

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 retained_intron

ENST00000356140, ENST00000392928, ENST00000485893, ENST00000498093, ENST00000904286, ENST00000904287, ENST00000904288, ENST00000904289, ENST00000904290, ENST00000904291

RefSeq mRNA: 2 — MANE Select: NM_138326 NM_001307983, NM_138326

CCDS: CCDS2173, CCDS77464

Canonical transcript exons

ENST00000356140 — 10 exons

Exon	Start	End
ENSE00001008748	134898341	134898439
ENSE00001008749	134872469	134872641
ENSE00001513633	134901798	134902034
ENSE00001875134	134838616	134838739
ENSE00003481401	134861969	134862018
ENSE00003520033	134863395	134863631
ENSE00003530502	134859261	134859357
ENSE00003547496	134870965	134871060
ENSE00003557487	134845233	134845277
ENSE00003675951	134867579	134867672

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 98.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4159 / max 158.5890, expressed in 35 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22626	0.1816	15
22625	0.1669	17
202400	0.0214	8
22623	0.0201	9
22624	0.0166	8
22622	0.0094	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.43	gold quality
right lobe of liver	UBERON:0001114	96.52	gold quality
liver	UBERON:0002107	96.21	gold quality
adult mammalian kidney	UBERON:0000082	95.54	gold quality
kidney	UBERON:0002113	90.63	gold quality
adult organism	UBERON:0007023	85.43	gold quality
renal medulla	UBERON:0000362	84.70	gold quality
cortex of kidney	UBERON:0001225	81.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.41	gold quality
gall bladder	UBERON:0002110	78.35	gold quality
metanephros cortex	UBERON:0010533	75.44	gold quality
metanephros	UBERON:0000081	71.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.12	gold quality
islet of Langerhans	UBERON:0000006	66.14	gold quality
pancreatic ductal cell	CL:0002079	64.64	silver quality
ileal mucosa	UBERON:0000331	59.92	silver quality
pancreas	UBERON:0001264	59.84	gold quality
right adrenal gland cortex	UBERON:0035827	59.69	gold quality
epithelial cell of pancreas	CL:0000083	59.63	gold quality
adrenal tissue	UBERON:0018303	59.37	gold quality
tibialis anterior	UBERON:0001385	59.14	silver quality
stromal cell of endometrium	CL:0002255	58.96	gold quality
body of pancreas	UBERON:0001150	57.99	gold quality
cerebellar cortex	UBERON:0002129	56.34	gold quality
cerebellar hemisphere	UBERON:0002245	56.31	gold quality
left ovary	UBERON:0002119	55.51	gold quality
right hemisphere of cerebellum	UBERON:0014890	55.44	gold quality
cerebellum	UBERON:0002037	55.20	gold quality
right adrenal gland	UBERON:0001233	55.14	gold quality
deltoid	UBERON:0001476	54.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	47.04
E-ANND-3	yes	8.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, PPARA

miRNA regulators (miRDB)

16 targeting ACMSD, 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-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-4298	97.26	66.59	765

Literature-anchored findings (GeneRIF, showing 8)

• identification and expression of cDNA (PMID:12140278)
• Limits production of the glutamatergic excitotoxin quinolinate, by diverting it to picolinate; inhibited by phthalates, by virtue of their structural similarity to nicotinate. (PMID:15229365)
• Data report a crystal structure of human ACMSD in complex with the glycolytic intermediate 1,3-dihydroxyacetonephosphate (DHAP),suggesting a regulatory link between NAD synthesis and glycolysis. (PMID:19843166)
• ACMSD is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. ACMSD mutation contributes to the development of Familial cortical myoclonic tremor and epilepsy. (PMID:23955123)
• The crystal structures of the human enzyme in its native catalytically active state, a substrate analogue-bound form and a selected active site mutant form with one of the putative substrate binding residues altered, are reported. (PMID:25392945)
• The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters. (PMID:27483383)
• This study shows that ACMSD is a key regulator of mammalian dietary niacin requirements and NAD(+) metabolism. (PMID:30380424)
• A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study. (PMID:36334154)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acmsd	ENSDARG00000062549
mus_musculus	Acmsd	ENSMUSG00000026348
rattus_norvegicus	Acmsd	ENSRNOG00000003884
caenorhabditis_elegans		WBGENE00022104

Protein

Protein identifiers

2-amino-3-carboxymuconate-6-semialdehyde decarboxylase — Q8TDX5 (reviewed: Q8TDX5)

Alternative names: Picolinate carboxylase

All UniProt accessions (2): Q8TDX5, A0A0S2Z681

UniProt curated annotations — full annotation on UniProt →

Function. Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolinate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.

Subunit / interactions. Monomer.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. ACMSD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDX5-1	1	yes
Q8TDX5-2	2

RefSeq proteins (2): NP_001294912, NP_612199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006680	Amidohydro-rel	Domain
IPR032465	ACMSD	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily

Pfam: PF04909

Enzyme classification (BRENDA):

• EC 4.1.1.45 — aminocarboxymuconate-semialdehyde decarboxylase (BRENDA: 8 organisms, 19 substrates, 42 inhibitors, 19 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-AMINO-3-(3-OXOPROP-2-ENYL)-BUT-2-ENEDIOATE	0.0065–0.0672	9
ALPHA-AMINO-BETA-CARBOXYMUCONATE-EPSILON-SEMIALD	0.0049–0.0921	4
2-AMINO-3-(3-OXOPROP-1-EN-1-YL)BUT-2-ENEDIOATE	0.001–0.0161	3
2-AMINO-3-CARBOXYMUCONATE-6-SEMIALDEHYDE	0.013–0.014	2
2-AMINOMUCONATE SEMIALDEHYDE	0.0033	1

Catalyzed reactions (Rhea), 1 shown:

• 2-amino-3-carboxymuconate 6-semialdehyde + H(+) = 2-aminomuconate 6-semialdehyde + CO2 (RHEA:16557)

UniProt features (43 total): helix 21, strand 12, binding site 5, turn 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4OFC	X-RAY DIFFRACTION	1.99
2WM1	X-RAY DIFFRACTION	2.01
4IGN	X-RAY DIFFRACTION	2.33
4IGM	X-RAY DIFFRACTION	2.39
4IH3	X-RAY DIFFRACTION	2.49
7PWY	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDX5-F1	97.67	0.99

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 6; 8; 47; 174; 291

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-71240	Tryptophan catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 82 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, NKX61_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_DICARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS

GO Biological Process (5): L-tryptophan catabolic process (GO:0006569), secondary metabolic process (GO:0019748), negative regulation of quinolinate biosynthetic process (GO:1904985), picolinic acid biosynthetic process (GO:1905004), regulation of ‘de novo’ NAD biosynthetic process from L-tryptophan (GO:1905012)

GO Molecular Function (7): aminocarboxymuconate-semialdehyde decarboxylase activity (GO:0001760), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), protein binding (GO:0005515), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
catalytic activity	2
aromatic amino acid catabolic process	1
indole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
metabolic process	1
negative regulation of biosynthetic process	1
quinolinate biosynthetic process	1
negative regulation of small molecule metabolic process	1
regulation of quinolinate biosynthetic process	1
monocarboxylic acid biosynthetic process	1
pyridine-containing compound biosynthetic process	1
regulation of amino acid metabolic process	1
‘de novo’ NAD+ biosynthetic process from L-tryptophan	1
regulation of purine nucleotide biosynthetic process	1
regulation of NAD metabolic process	1
carboxy-lyase activity	1
transition metal ion binding	1
binding	1
carbon-carbon lyase activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACMSD	QPRT	Q15274	840
ACMSD	HAAO	P46952	811
ACMSD	KYNU	Q16719	795
ACMSD	CCDC62	Q6P9F0	777
ACMSD	MCCC1	Q96RQ3	762
ACMSD	TDO2	P48775	759
ACMSD	KMO	O15229	754
ACMSD	AFMID	Q63HM1	670
ACMSD	SYT12	Q8IV01	668
ACMSD	SYT11	Q9BT88	662
ACMSD	STK39	Q9UEW8	653
ACMSD	HIP1R	O75146	631
ACMSD	GAK	O14976	619
ACMSD	AADAT	Q8N5Z0	594
ACMSD	TMEM163	Q8TC26	571

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MAGEA11	ACMSD	psi-mi:“MI:0915”(physical association)	0.560
ACMSD	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
ACMSD	CCT6B	psi-mi:“MI:0915”(physical association)	0.400
PLIN3	ACMSD	psi-mi:“MI:0915”(physical association)	0.370
MAGEA11	ACMSD	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (7): ACMSD (Two-hybrid), ACMSD (Two-hybrid), CDK20 (Affinity Capture-MS), MAGEA11 (Two-hybrid), ACMSD (Two-hybrid), GPSM3 (Two-hybrid), CCT6B (Affinity Capture-MS)

ESM2 similar proteins: A0A223HDI5, A3QK15, O00097, P00333, P00504, P04181, P04182, P07754, P08843, P0C0Y4, P0C0Y5, P12863, P14219, P14673, P14674, P14675, P25141, P28032, P29401, P29758, P33097, P34937, P37769, P40142, P41177, P41747, P46226, P48491, P48493, P48494, P48495, P49724, P50137, Q05528, Q07264, Q0II68, Q29RZ0, Q2R8Z5, Q2U919, Q3ZCF5

Diamond homologs: P83662, Q0II68, Q54LN9, Q8R519, Q8R5M5, Q8TDX5, Q8T8B9, G2IQQ5, P0CT50, P80402, Q0SFL6, Q12BV1, Q5AUW9, Q60FX6, Q60GU1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	53
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
147544	GRCh38/hg38 2q14.3-22.1(chr2:123445762-140592538)x1	Pathogenic
1679114	GRCh37/hg19 2q13-22.3(chr2:112475655-145691999)x3	Pathogenic
441676	GRCh37/hg19 2q14.2-22.1(chr2:120571363-141627287)x1	Pathogenic
60184	GRCh38/hg38 2q14.1-21.3(chr2:118086324-134964738)x1	Pathogenic
686222	GRCh37/hg19 2q21.2-22.1(chr2:133457177-138188195)x1	Pathogenic
3062608	GRCh37/hg19 2q21.2-23.2(chr2:134589311-149951291)x3	Likely pathogenic

SpliceAI

1640 predictions. Top by Δscore:

Variant	Effect	Δscore
2:134863629:GCG:G	donor_gain	1.0000
2:134863629:GCGGT:G	donor_loss	1.0000
2:134863633:T:A	donor_loss	1.0000
2:134898435:CAAAG:C	donor_loss	1.0000
2:134898436:AAAG:A	donor_loss	1.0000
2:134898437:AAGGT:A	donor_loss	1.0000
2:134898438:AGGTA:A	donor_loss	1.0000
2:134898439:GG:G	donor_loss	1.0000
2:134898440:G:GA	donor_loss	1.0000
2:134898441:T:A	donor_loss	1.0000
2:134838737:AAG:A	donor_loss	0.9900
2:134838738:AG:A	donor_loss	0.9900
2:134838739:GGTA:G	donor_loss	0.9900
2:134838740:G:T	donor_loss	0.9900
2:134844348:T:G	acceptor_gain	0.9900
2:134844357:A:G	acceptor_gain	0.9900
2:134845228:TGCAG:T	acceptor_gain	0.9900
2:134845230:CAG:C	acceptor_gain	0.9900
2:134845231:AGA:A	acceptor_gain	0.9900
2:134845232:GAG:G	acceptor_gain	0.9900
2:134863383:T:TA	acceptor_gain	0.9900
2:134863390:A:AG	acceptor_gain	0.9900
2:134863390:ACCAG:A	acceptor_gain	0.9900
2:134863391:C:G	acceptor_gain	0.9900
2:134863393:A:AG	acceptor_gain	0.9900
2:134863393:A:C	acceptor_loss	0.9900
2:134863394:G:GA	acceptor_gain	0.9900
2:134863394:G:GC	acceptor_loss	0.9900
2:134863394:GGCC:G	acceptor_gain	0.9900
2:134863394:GGCCA:G	acceptor_gain	0.9900

AlphaMissense

2230 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:134867612:C:G	H174D	0.997
2:134898363:A:T	D291V	0.997
2:134898371:T:C	F294L	0.995
2:134898373:T:A	F294L	0.995
2:134898373:T:G	F294L	0.995
2:134898362:G:C	D291H	0.994
2:134867614:T:A	H174Q	0.993
2:134867614:T:G	H174Q	0.993
2:134898364:T:A	D291E	0.993
2:134898364:T:G	D291E	0.993
2:134838704:C:G	H8D	0.992
2:134872519:C:A	R243S	0.992
2:134838706:T:A	H8Q	0.990
2:134838706:T:G	H8Q	0.990
2:134867613:A:G	H174R	0.990
2:134872508:G:A	G239E	0.990
2:134867612:C:A	H174N	0.989
2:134870968:T:C	M195T	0.989
2:134871047:T:G	C221W	0.989
2:134861999:C:A	P77H	0.988
2:134867663:T:A	W191R	0.988
2:134867663:T:C	W191R	0.988
2:134871045:T:C	C221R	0.988
2:134871054:C:G	H224D	0.988
2:134872496:G:C	R235T	0.988
2:134872497:A:C	R235S	0.988
2:134872497:A:T	R235S	0.988
2:134898362:G:T	D291Y	0.988
2:134898363:A:G	D291G	0.988
2:134872585:G:C	D265H	0.987

dbSNP variants (sampled 300 via entrez): RS1000022171 (2:134848339 C>T), RS1000053825 (2:134867484 T>C), RS1000136199 (2:134848608 C>T), RS1000231600 (2:134879394 C>T), RS1000256834 (2:134902297 G>A), RS1000288226 (2:134901929 G>A,T), RS1000337302 (2:134872847 G>A), RS1000338345 (2:134865179 T>C), RS1000415737 (2:134862275 C>T), RS1000628332 (2:134884561 G>T), RS1000658838 (2:134854983 C>A), RS1000725972 (2:134871177 A>G), RS1000765931 (2:134875471 A>C), RS1000807548 (2:134889301 C>T), RS1000820558 (2:134844522 G>A)

Disease associations

OMIM: gene MIM:608889 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Limited	Autosomal dominant

Mondo (1): epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000959_5	Parkinson’s disease	7.000000e-09
GCST001762_451	Obesity-related traits	7.000000e-07
GCST002544_13	Parkinson’s disease	9.000000e-20
GCST002875_17	Diisocyanate-induced asthma	6.000000e-07
GCST004003_1	Hematocrit	2.000000e-11
GCST005830_22	Hand grip strength	6.000000e-14
GCST005951_43	Body mass index	5.000000e-09
GCST006896_4	Free thyroxine concentration	9.000000e-09
GCST010243_81	Apolipoprotein B levels	8.000000e-11
GCST010245_120	LDL cholesterol levels	6.000000e-12
GCST90002403_118	Red blood cell count	3.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0006995	response to diisocyanate
EFO:0004348	hematocrit
EFO:0006941	grip strength measurement
EFO:0004340	body mass index
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105941 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 54,786 (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
CHEMBL898	DIFLUNISAL	4	54,786

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

Binding affinities (BindingDB)

22 measured of 22 human assays (22 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-oxo-2-[[3-(2H-tetrazol-5-yl)phenyl]methylsulfanyl]-6-thiophen-2-yl-5H-pyrimidine-5-carbonitrile	IC50	5 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
2-[3-[(5-cyano-4-oxo-6-thiophen-2-yl-1,3-diazinan-2-yl)sulfanylmethyl]phenyl]acetic acid	IC50	10 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-oxo-6-thiophen-2-yl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	12 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
4-oxo-2-[[3-(5-oxo-1,2,4-oxadiazolidin-3-yl)phenyl]methylsulfanyl]-6-thiophen-2-yl-5H-pyrimidine-5-carbonitrile	IC50	25 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-oxo-6-thiophen-3-yl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	31 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[[5-cyano-4-oxo-6-(1,3-thiazol-2-yl)-1,3-diazinan-2-yl]sulfanylmethyl]benzoic acid	IC50	49 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-oxo-6-phenyl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	50 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[[5-cyano-4-(furan-2-yl)-6-oxo-1,3-diazinan-2-yl]sulfanylmethyl]benzoic acid	IC50	66 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-bromo-4-oxo-6-phenyl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	71 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-cyclohexyl-6-oxo-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	77 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-oxo-6-pyridin-4-yl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	82 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
4-[[4-(4-chlorophenyl)-5-cyano-6-oxo-1,3-diazinan-2-yl]sulfanylmethyl]benzoic acid	IC50	82 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-bromo-4-oxo-6-thiophen-2-yl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	88 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
4-[(5-cyano-4-oxo-6-phenyl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	110 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-chloro-4-oxo-6-phenyl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	136 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(4-oxo-6-phenyl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	740 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(4-oxo-6-thiophen-2-yl-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	760 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
ethyl 3-[[5-cyano-4-(4-methylphenyl)-6-oxo-1,3-diazinan-2-yl]sulfanylmethyl]benzoate	IC50	960 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(4-chloro-5-cyano-6-phenylpyrimidin-2-yl)sulfanylmethyl]benzoic acid	IC50	1100 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
3-[(5-cyano-4-methyl-6-oxo-1,3-diazinan-2-yl)sulfanylmethyl]benzoic acid	IC50	1700 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
2-[(5-cyano-4-oxo-6-phenyl-5H-pyrimidin-2-yl)sulfanyl]propanoic acid	IC50	1990 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase
2-[(5-cyano-4-oxo-6-thiophen-2-yl-1,3-diazinan-2-yl)sulfanyl]-N-(2-hydroxyphenyl)acetamide	IC50	4900 nM	US-9708272: Inhibitors of α-amino-β-carboxymuconic acid semialdehyde decarboxylase

ChEMBL bioactivities

77 potent at pChembl≥5 of 88 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL4072240
8.30	IC50	5	nM	CHEMBL4072240
8.00	IC50	10	nM	CHEMBL4071212
7.92	IC50	12	nM	CHEMBL4100715
7.89	IC50	13	nM	CHEMBL4071212
7.89	IC50	13	nM	CHEMBL4796997
7.70	IC50	20	nM	CHEMBL4100715
7.60	IC50	25	nM	CHEMBL4553502
7.51	IC50	31	nM	CHEMBL4578242
7.35	IC50	45	nM	CHEMBL4067706
7.31	IC50	49	nM	CHEMBL4437596
7.30	IC50	50	nM	CHEMBL4067706
7.18	IC50	66	nM	CHEMBL4580504
7.15	IC50	71	nM	CHEMBL4097581
7.11	IC50	77	nM	CHEMBL4066693
7.11	IC50	78	nM	CHEMBL4796997
7.09	IC50	82	nM	CHEMBL4470922
7.09	IC50	82	nM	CHEMBL4465329
7.06	IC50	88	nM	CHEMBL4458077
7.05	IC50	89	nM	CHEMBL4066693
7.00	IC50	99	nM	CHEMBL4097581
7.00	IC50	100	nM	CHEMBL4530672
7.00	IC50	100	nM	CHEMBL4465713
7.00	IC50	100	nM	CHEMBL4458019
7.00	IC50	100	nM	CHEMBL4451963
7.00	IC50	100	nM	CHEMBL4531966
7.00	IC50	100	nM	CHEMBL4466867
7.00	IC50	100	nM	CHEMBL4447852
7.00	IC50	100	nM	CHEMBL4442862
6.96	IC50	110	nM	CHEMBL4449573
6.87	IC50	136	nM	CHEMBL4070405
6.82	IC50	151	nM	CHEMBL4070405
6.50	IC50	316	nM	CHEMBL4088930
6.13	IC50	740	nM	CHEMBL4061780
6.12	IC50	760	nM	CHEMBL4448895
6.02	IC50	960	nM	CHEMBL4530111
6.00	IC50	1000	nM	CHEMBL4464696
6.00	IC50	1000	nM	CHEMBL4514322
5.98	IC50	1055	nM	CHEMBL4061780
5.96	IC50	1100	nM	CHEMBL4088930
5.88	IC50	1320	nM	CHEMBL3126314
5.77	IC50	1700	nM	CHEMBL4067044
5.76	IC50	1746	nM	CHEMBL4082726
5.72	IC50	1899	nM	CHEMBL4067044
5.70	IC50	1990	nM	CHEMBL4459014
5.59	Ki	2560	nM	DIFLUNISAL
5.51	IC50	3100	nM	CHEMBL4798885
5.48	IC50	3290	nM	CHEMBL419420
5.47	IC50	3350	nM	CHEMBL4093002
5.37	IC50	4290	nM	CHEMBL121772

PubChem BioAssay actives

23 with measured affinity, of 88 total; 21 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-oxo-2-[[3-(2H-tetrazol-5-yl)phenyl]methylsulfanyl]-4-thiophen-2-yl-1H-pyrimidine-5-carbonitrile	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0030	uM
2-[3-[(5-cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]phenyl]acetic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0130	uM
2-[3-[(5-cyano-4-oxo-6-thiophen-2-yl-2,3-dihydro-1H-pyrimidin-2-yl)sulfanylmethyl]phenyl]acetic acid	1744123: Inhibition of ACMSD (unknown origin)	ic50	0.0130	uM
3-[(5-cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0200	uM
3-[(5-cyano-6-oxo-4-phenyl-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0450	uM
3-[(5-cyano-4-cyclohexyl-6-oxo-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0890	uM
3-[(5-bromo-6-oxo-4-phenyl-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.0990	uM
3-[(5-chloro-6-oxo-4-phenyl-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.1510	uM
3-[(4-chloro-5-cyano-6-phenylpyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	0.3160	uM
3-[(6-oxo-4-phenyl-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	1.0550	uM
2-hydroxy-5-naphthalen-1-ylbenzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	1.3200	uM
3-[(5-cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]-N-hydroxybenzamide	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	1.7460	uM
3-[(5-cyano-4-methyl-6-oxo-1H-pyrimidin-2-yl)sulfanylmethyl]benzoic acid	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	1.8990	uM
Diflunisal	1744124: Competitive inhibition of human ACMSD using ACMS substrate by spectrometry	ki	2.5600	uM
2-hydroxy-5-(3-phenylphenyl)benzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	3.1000	uM
5-(2-fluorophenyl)-2-hydroxybenzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	3.2900	uM
6-oxo-4-thiophen-2-yl-2-[[3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methylsulfanyl]-1H-pyrimidine-5-carbonitrile	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	3.3500	uM
2-hydroxy-5-phenylbenzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	4.2900	uM
2-benzylsulfanyl-6-oxo-4-phenyl-1H-pyrimidine-5-carbonitrile	1473526: Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	ic50	4.4500	uM
5-(3-benzylphenyl)-2-hydroxybenzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	4.6100	uM
2-hydroxy-5-naphthalen-2-ylbenzoic acid	1744125: Inhibition of human ACMSD using ACMS substrate by spectrometry	ic50	8.8300	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Cyclosporine	decreases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
kojic acid	decreases expression	1
sodium arsenite	decreases expression	1
pentanal	decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Arbutin	decreases expression	1
Estradiol	decreases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases methylation, decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4028573	Binding	Inhibition of human ACMSD expressed in Pichia pastoris using ACMS as substrate by coupled spectrophotometric assay	α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy