ME3

Summary

ME3 (malic enzyme 3, HGNC:6985) is a protein-coding gene on chromosome 11q14.2, encoding NADP-dependent malic enzyme, mitochondrial (Q16798). Catalyzes the oxidative decarboxylation of (S)-malate to pyruvate using NADP(+) as a cofactor.

Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.

Source: NCBI Gene 10873 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 77 total
• Druggable target: yes
• MANE Select transcript: NM_001161586

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6985
Approved symbol	ME3
Name	malic enzyme 3
Location	11q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151376
Ensembl biotype	protein_coding
OMIM	604626
Entrez	10873

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000323418, ENST00000393324, ENST00000525957, ENST00000526504, ENST00000526834, ENST00000526944, ENST00000530335, ENST00000530520, ENST00000532471, ENST00000534638, ENST00000543262, ENST00000875288, ENST00000875289, ENST00000875290, ENST00000951025, ENST00000951026, ENST00000951027

RefSeq mRNA: 5 — MANE Select: NM_001161586 NM_001014811, NM_001161586, NM_001351934, NM_001395868, NM_006680

CCDS: CCDS8277

Canonical transcript exons

ENST00000543262 — 15 exons

Exon	Start	End
ENSE00000999241	86441108	86441440
ENSE00000999243	86442821	86442919
ENSE00000999244	86447065	86447207
ENSE00000999245	86446314	86446487
ENSE00003487813	86497963	86498124
ENSE00003492111	86487337	86487440
ENSE00003594172	86556553	86556702
ENSE00003602052	86448150	86448255
ENSE00003610666	86508792	86508867
ENSE00003617809	86559690	86559823
ENSE00003625356	86465091	86465200
ENSE00003643302	86449889	86450002
ENSE00003666539	86450301	86450398
ENSE00003794570	86671762	86671958
ENSE00003978311	86672324	86672616

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 92.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0189 / max 462.9354, expressed in 1484 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121737	5.0681	1292
121740	2.9692	901
121736	2.6909	960
121739	2.1122	917
121741	1.1794	340
121738	0.6778	377
206409	0.1918	111
121742	0.0871	28
121735	0.0425	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.67	gold quality
left ovary	UBERON:0002119	91.78	gold quality
adenohypophysis	UBERON:0002196	91.75	gold quality
nasal cavity epithelium	UBERON:0005384	91.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.21	gold quality
pituitary gland	UBERON:0000007	91.03	gold quality
right ovary	UBERON:0002118	90.97	gold quality
right adrenal gland cortex	UBERON:0035827	90.89	gold quality
endocervix	UBERON:0000458	90.76	gold quality
left adrenal gland cortex	UBERON:0035825	90.53	gold quality
left adrenal gland	UBERON:0001234	90.52	gold quality
caudate nucleus	UBERON:0001873	90.41	gold quality
heart left ventricle	UBERON:0002084	90.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.40	gold quality
right adrenal gland	UBERON:0001233	90.37	gold quality
adrenal cortex	UBERON:0001235	90.34	gold quality
nucleus accumbens	UBERON:0001882	90.32	gold quality
putamen	UBERON:0001874	90.23	gold quality
prefrontal cortex	UBERON:0000451	90.21	gold quality
cardiac ventricle	UBERON:0002082	90.21	gold quality
right frontal lobe	UBERON:0002810	90.14	gold quality
body of stomach	UBERON:0001161	90.08	gold quality
body of uterus	UBERON:0009853	89.86	gold quality
fundus of stomach	UBERON:0001160	89.57	gold quality
lateral globus pallidus	UBERON:0002476	89.56	gold quality
cortical plate	UBERON:0005343	89.48	gold quality
adrenal gland	UBERON:0002369	89.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.16	gold quality
stomach	UBERON:0000945	89.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	49.22
E-ANND-3	yes	3.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, ASCL2, ATOH8, DLX2, DNMT1, DNMT3B, EED, ESR1, EZH2, GATA4, HOXD4, ID1, IRF1, IRF8, KDM5A, KDM5B, KDM5C, KLF11, KMT2A, MBD2, MEF2A, NEUROD4, NFATC1, NFE2L2, NFKB1, NFKB, NFYA, NKX2-5, NR1H4, OTX2, PARP1, RARG, RELA, SMAD1, SMAD6, SP1, SP7, SPI1, STAT2, STAT5A

miRNA regulators (miRDB)

11 targeting ME3, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4323	93.93	63.89	656

Literature-anchored findings (GeneRIF, showing 7)

• ATP inhibition is proposed to be determined by the electrostatic potential involving the positive charge on the side chain of Lys346 (PMID:18959763)
• Studies demonstrate that the Lys57 residue plays dual functional roles in the structural integrity of the allosteric site and in the subunit-subunit interaction at the dimer interface of m-NAD(P)-ME. (PMID:19236308)
• human c-NADP-ME exists mainly as a tetramer, whereas human m-NAD(P)-ME exists as a mixture of dimers and tetramers (PMID:19416979)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• ME3 is extensively involved in carcinogenesis of pancreatic cancer (PMID:31607129)
• Adaptive and Constitutive Activations of Malic Enzymes Confer Liver Cancer Multilayered Protection Against Reactive Oxygen Species. (PMID:33619771)
• Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1alpha stabilization. (PMID:39212717)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	me3	ENSDARG00000002305
mus_musculus	Me3	ENSMUSG00000030621
rattus_norvegicus	Me3	ENSRNOG00000017311
drosophila_melanogaster	Men	FBGN0002719
drosophila_melanogaster	Menl-2	FBGN0029153
drosophila_melanogaster	Menl-1	FBGN0029154
drosophila_melanogaster	Men-b	FBGN0029155
drosophila_melanogaster	CG7848	FBGN0034127
caenorhabditis_elegans		WBGENE00012983

Paralogs (2): ME1 (ENSG00000065833), ME2 (ENSG00000082212)

Protein

Protein identifiers

NADP-dependent malic enzyme, mitochondrial — Q16798 (reviewed: Q16798)

Alternative names: Malic enzyme 3

All UniProt accessions (5): E9PKA0, E9PND9, E9PNN2, Q16798, Q6TCH8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the oxidative decarboxylation of (S)-malate to pyruvate using NADP(+) as a cofactor. Can also reverse the decarboxylation reaction, but only with significantly lower efficiency.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Expressed predominantly in organs with a low-division rate.

Cofactor. Divalent metal cations. Prefers magnesium or manganese.

Similarity. Belongs to the malic enzymes family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16798-1	1	yes
Q16798-2	2

RefSeq proteins (5): NP_001014811, NP_001155058, NP_001338863, NP_001382797, NP_006671 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001891	Malic_OxRdtase	Family
IPR012301	Malic_N_dom	Domain
IPR012302	Malic_NAD-bd	Domain
IPR015884	Malic_enzyme_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR037062	Malic_N_dom_sf	Homologous_superfamily
IPR046346	Aminoacid_DH-like_N_sf	Homologous_superfamily

Pfam: PF00390, PF03949

Catalyzed reactions (Rhea), 2 shown:

• oxaloacetate + H(+) = pyruvate + CO2 (RHEA:15641)
• (S)-malate + NADP(+) = pyruvate + CO2 + NADPH (RHEA:18253)

UniProt features (72 total): helix 34, strand 14, binding site 6, turn 6, splice variant 2, sequence variant 2, active site 2, transit peptide 1, chain 1, site 1, modified residue 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8EYN	X-RAY DIFFRACTION	1.94
8EYO	X-RAY DIFFRACTION	2.49
8E76	ELECTRON MICROSCOPY	2.51
8E78	ELECTRON MICROSCOPY	2.77
8E8O	ELECTRON MICROSCOPY	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16798-F1	92.20	0.87

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 (3): 304 (important for activity); 137 (proton donor); 208 (proton acceptor)

Ligand- & substrate-binding residues (6): 443; 190; 280; 281; 304; 304

Post-translational modifications (1): 371

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 138 (showing top): JI_RESPONSE_TO_FSH_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_528, TGACCTY_ERR1_Q2, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, CEBPB_01, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CDP_01, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, BROWNE_HCMV_INFECTION_14HR_DN, MOOTHA_GLUCONEOGENESIS, BASSO_HAIRY_CELL_LEUKEMIA_UP

GO Biological Process (2): malate metabolic process (GO:0006108), pyruvate biosynthetic process (GO:0042866)

GO Molecular Function (9): malic enzyme activity (GO:0004470), malate dehydrogenase (decarboxylating) (NADP+) activity (GO:0004473), oxaloacetate decarboxylase activity (GO:0008948), metal ion binding (GO:0046872), NAD binding (GO:0051287), NADP+ binding (GO:0070401), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), NADP binding (GO:0050661)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adenyl nucleotide binding	2
dicarboxylic acid metabolic process	1
pyruvate metabolic process	1
monocarboxylic acid biosynthetic process	1
malate dehydrogenase activity	1
malic enzyme activity	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
carboxy-lyase activity	1
cation binding	1
anion binding	1
NADP binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ME3	PGD	P52209	750
ME3	H6PD	O95479	736
ME3	G6PD	P11413	735
ME3	MDH2	P40926	728
ME3	IDH2	P48735	609
ME3	PC	P11498	584
ME3	IDH1	O75874	582
ME3	GPI	P06744	569
ME3	RPIA	P49247	550
ME3	ACLY	P53396	541
ME3	ACACB	O00763	516
ME3	HSPA4	P34932	512
ME3	PCK2	Q16822	509
ME3	PGC	P20142	506
ME3	CS	O75390	500

IntAct

2 interactions, top by confidence:

A	B	Type	Score
RUNX1	ME3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): ME3 (Reconstituted Complex), CAB39 (Co-fractionation), ME3 (Affinity Capture-MS), ME3 (Negative Genetic), ME3 (Synthetic Lethality), ME3 (Two-hybrid)

ESM2 similar proteins: A1A4Q2, A6NEY8, A6QP05, O80526, P11172, P12081, P13439, P31754, P37111, P38918, P47897, Q02053, Q16798, Q28EX9, Q2KI84, Q2KJD7, Q32LQ4, Q3MHH4, Q502H1, Q53JY8, Q5FWT7, Q5R4A0, Q5R4C4, Q5R4R2, Q5R514, Q5R8R4, Q5RGJ5, Q5U300, Q5ZJJ8, Q61035, Q641F1, Q66H61, Q6DI37, Q6DIJ1, Q6IQS6, Q6NRL0, Q7ZVX6, Q8BGR9, Q8BML9, Q8C878

Diamond homologs: A0KHR8, A0KT69, A1JTY5, A1RNF8, A1S8W7, A3D0E1, A3QH80, A4SKE9, A4TKN8, A4WAJ3, A4Y3I1, A5F1Z0, A6V1V5, A6WSH0, A7FJK4, A7N025, A7ZLS1, A8AGN6, A8FZ49, A8GC31, A8H7G5, A9L2F4, A9MR05, A9MYU8, B0TRQ2, B1JPZ6, B1KFN0, B2JZJ5, B4ESY2, B4T5V6, B4TII8, B4TW15, B5F5W5, B5FHJ6, B5QTN6, B5RAB4, B5Z1T9, B7L7H9, B7UWK9, B8CQT6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4145 predictions. Top by Δscore:

Variant	Effect	Δscore
11:86442819:A:AC	donor_gain	1.0000
11:86442820:C:CC	donor_gain	1.0000
11:86446309:GATAC:G	donor_loss	1.0000
11:86446310:ATAC:A	donor_loss	1.0000
11:86446311:TACCT:T	donor_loss	1.0000
11:86446313:CCT:C	donor_gain	1.0000
11:86446315:T:TA	donor_gain	1.0000
11:86446339:T:C	donor_gain	1.0000
11:86446483:CGGCC:C	acceptor_gain	1.0000
11:86447055:C:CA	donor_gain	1.0000
11:86447056:C:A	donor_gain	1.0000
11:86447085:T:TA	donor_gain	1.0000
11:86447206:ACCT:A	acceptor_loss	1.0000
11:86447208:C:CA	acceptor_loss	1.0000
11:86447209:T:G	acceptor_loss	1.0000
11:86448185:T:TA	donor_gain	1.0000
11:86448251:CTCCC:C	acceptor_gain	1.0000
11:86448253:CCC:C	acceptor_gain	1.0000
11:86448254:CCC:C	acceptor_gain	1.0000
11:86448255:CCTAC:C	acceptor_loss	1.0000
11:86448256:C:CC	acceptor_gain	1.0000
11:86448257:T:G	acceptor_loss	1.0000
11:86465086:CCTA:C	donor_loss	1.0000
11:86465087:CTAC:C	donor_loss	1.0000
11:86465088:TAC:T	donor_loss	1.0000
11:86465089:A:C	donor_loss	1.0000
11:86465090:C:CA	donor_loss	1.0000
11:86465197:AAACC:A	acceptor_loss	1.0000
11:86465198:AACCT:A	acceptor_loss	1.0000
11:86465199:ACCT:A	acceptor_loss	1.0000

AlphaMissense

3952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:86446401:A:C	N489K	1.000
11:86446401:A:T	N489K	1.000
11:86446404:G:C	N488K	1.000
11:86446404:G:T	N488K	1.000
11:86465099:T:A	D304V	1.000
11:86465099:T:G	D304A	1.000
11:86465102:T:A	D303V	1.000
11:86465102:T:G	D303A	1.000
11:86465103:C:G	D303H	1.000
11:86446385:C:A	G495W	0.999
11:86446389:G:C	F493L	0.999
11:86446389:G:T	F493L	0.999
11:86446391:A:G	F493L	0.999
11:86447116:G:C	N443K	0.999
11:86447116:G:T	N443K	0.999
11:86447119:G:C	S442R	0.999
11:86447119:G:T	S442R	0.999
11:86447121:T:G	S442R	0.999
11:86449980:A:G	L347P	0.999
11:86450392:G:T	A309D	0.999
11:86465091:C:G	G307R	0.999
11:86465098:G:C	D304E	0.999
11:86465098:G:T	D304E	0.999
11:86465099:T:C	D304G	0.999
11:86465100:C:G	D304H	0.999
11:86465101:A:C	D303E	0.999
11:86465101:A:T	D303E	0.999
11:86465102:T:C	D303G	0.999
11:86465103:C:A	D303Y	0.999
11:86465104:A:C	N302K	0.999

dbSNP variants (sampled 300 via entrez): RS1000031131 (11:86542815 T>C), RS1000048741 (11:86669545 G>A,C), RS1000080376 (11:86502820 C>T), RS1000081195 (11:86496262 T>C), RS1000082688 (11:86525112 A>G), RS1000103475 (11:86559434 C>T), RS1000111015 (11:86521319 C>A,G,T), RS1000121166 (11:86477245 G>A), RS1000149041 (11:86617197 T>C), RS1000164281 (11:86538125 GGAAT>G), RS1000182289 (11:86616840 C>T), RS1000189386 (11:86472882 T>C), RS1000218145 (11:86640832 T>C), RS1000218982 (11:86560551 G>A,T), RS1000219618 (11:86657265 A>G)

Disease associations

OMIM: gene MIM:604626 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST002009_1	Adverse response to chemotherapy (neutropenia/leucopenia) (doxorubicin)	7.000000e-06
GCST002177_7	Adverse response to chemotherapy in breast cancer (alopecia) (anti-microtubule)	2.000000e-06
GCST002828_6	Urate levels in obese individuals	9.000000e-06
GCST004032_8	JT interval (sulfonylurea treatment interaction)	6.000000e-08
GCST004183_16	Lung function (FEV1)	9.000000e-09
GCST005580_252	Intraocular pressure	2.000000e-10
GCST005580_268	Intraocular pressure	4.000000e-10
GCST006394_91	Intraocular pressure	2.000000e-14
GCST006395_7	Glaucoma	4.000000e-06
GCST006412_124	Intraocular pressure	7.000000e-16
GCST007100_2	Asthma exacerbations in inhaled corticosteroid treatment	2.000000e-07
GCST007100_9	Asthma exacerbations in inhaled corticosteroid treatment	4.000000e-06
GCST009310_16	Sensorimotor dexterity	5.000000e-06
GCST009725_27	Intraocular pressure	2.000000e-14
GCST009870_14	Calcific aortic valve stenosis	3.000000e-06
GCST010002_244	Refractive error	2.000000e-53
GCST011441_10	Glaucoma (high intraocular pressure)	3.000000e-09
GCST90002390_38	Mean corpuscular hemoglobin	4.000000e-10
GCST90002392_354	Mean corpuscular volume	3.000000e-09
GCST90002396_473	Mean reticulocyte volume	1.000000e-10
GCST90002397_535	Mean spheric corpuscular volume	4.000000e-09
GCST90002404_520	Red cell distribution width	6.000000e-11
GCST90011770_57	Glaucoma (primary open-angle)	6.000000e-21

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005260	response to antimicrotubule agent
EFO:0004531	urate measurement
EFO:0007885	JT interval
EFO:0007922	response to sulfonylurea
EFO:0004314	forced expiratory volume
EFO:0004695	intraocular pressure measurement
EFO:0007614	asthma exacerbation measurement
EFO:0008354	cognitive function measurement
EFO:0000266	aortic stenosis
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6182 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2125362	ME3		0.00	0

ChEMBL bioactivities

30 potent at pChembl≥5 of 31 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL5284610
7.16	IC50	70	nM	CHEMBL5285899
7.10	IC50	80	nM	CHEMBL5275653
7.05	IC50	90	nM	CHEMBL5287773
7.00	IC50	100	nM	CHEMBL5284469
7.00	IC50	100	nM	CHEMBL5289840
6.96	IC50	110	nM	CHEMBL5289950
6.96	IC50	110	nM	CHEMBL5278951
6.92	IC50	120	nM	CHEMBL5277536
6.89	IC50	130	nM	CHEMBL5279230
6.89	IC50	130	nM	CHEMBL5279096
6.89	IC50	130	nM	CHEMBL5288731
6.85	IC50	140	nM	CHEMBL5273550
6.82	IC50	150	nM	CHEMBL372408
6.82	IC50	150	nM	CHEMBL5267542
6.80	IC50	160	nM	CHEMBL5279589
6.70	IC50	200	nM	CHEMBL5278596
6.64	IC50	230	nM	CHEMBL5281297
6.62	IC50	240	nM	CHEMBL5286488
6.60	IC50	250	nM	CHEMBL5290463
6.51	IC50	310	nM	CHEMBL5274945
6.48	IC50	330	nM	CHEMBL5283020
6.44	IC50	360	nM	CHEMBL5286064
6.41	IC50	390	nM	CHEMBL5291081
6.39	IC50	410	nM	CHEMBL5282439
6.33	IC50	470	nM	CHEMBL5270965
6.24	IC50	580	nM	CHEMBL5281258
6.05	IC50	900	nM	CHEMBL5218866
5.29	IC50	5100	nM	CHEMBL5283717
5.25	IC50	5600	nM	CHEMBL5277143

PubChem BioAssay actives

30 with measured affinity, of 80 total; 30 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
3-(4-butoxyphenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.0600	uM
N-[1-(4-hydroxyphenyl)piperidin-4-yl]-2-phenylacetamide	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.0700	uM
(E)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-phenylprop-2-en-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.0800	uM
2-(4-fluorophenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.0900	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-phenylethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1000	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-phenylpropan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1000	uM
4-(4-hydroxyphenyl)-N-phenylpiperazine-1-carboxamide	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1100	uM
2-[4-(4-hydroxyphenyl)piperazin-1-yl]-N-phenylacetamide	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1100	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-methyl-3-phenylbutan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1200	uM
1-(4-hydroxyphenyl)-N-phenylpiperidine-4-carboxamide	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1300	uM
2-(4-chlorophenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1300	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-phenoxyethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1300	uM
3-(4-chlorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1400	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methyl-3-phenylbutan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1500	uM
3-[4-(4-hydroxyphenyl)piperazin-1-yl]-1-phenylpyrrolidine-2,5-dione	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1500	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-thiophen-2-ylpropan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1600	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-2-phenylethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2000	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-phenylpropan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2300	uM
3-(1-benzothiophen-2-yl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2400	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-(5-phenylthiophen-2-yl)propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2500	uM
3-(4-fluorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methylbutan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3100	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-[4-(trifluoromethyl)phenyl]ethanone	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3300	uM
3-(4-chlorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methylbutan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3600	uM
3-(4-butoxyphenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3900	uM
3-(4-fluorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.4100	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-(4-methoxyphenyl)propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.4700	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-[4-(2-methoxyethoxy)phenyl]propan-1-one	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.5800	uM
2,5-dihydroxy-3,6-bis(4-methoxyphenyl)cyclohexa-2,5-diene-1,4-dione	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.9000	uM
2-phenyl-N-(2H-tetrazol-5-yl)quinoline-4-carboxamide	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	5.1000	uM
3-[(3-carboxy-2-hydroxynaphthalen-1-yl)methyl]-2-hydroxynaphthalene-1-carboxylic acid	1922682: Inhibition of His-tagged human recombinant ME3 (26 to 604 residues) using L-malate and beta-NADP+ as substrate preincubated with enzyme for 5 mins followed by beta-NADP+ challenge and incubated under shaking for 5 mins followed by incubation for 3 hrs without shaking by resorufin dye based fluorescence analysis	ic50	5.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	affects expression, increases abundance, decreases methylation, affects cotreatment	2
cobaltous chloride	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
methylmercuric chloride	decreases expression	1
kojic acid	decreases expression	1
terbufos	increases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1053220	Binding	Activation of human recombinant mitochondrial NADP-ME expressed in Escherichia coli BL21 assessed as residual enzyme activity by spectrophotometry in presence of fumarate	Effects of structural analogues of the substrate and allosteric regulator of the human mitochondrial NAD(P)+-dependent malic enzyme. — Bioorg Med Chem

Clinical trials (associated diseases)

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