SLC16A1

Summary

SLC16A1 (solute carrier family 16 member 1, HGNC:10922) is a protein-coding gene on chromosome 1p13.2, encoding Monocarboxylate transporter 1 (P53985). Bidirectional proton-coupled monocarboxylate transporter. It is a selective cancer dependency (DepMap: 11.7% of cell lines).

The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 6566 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ketoacidosis due to monocarboxylate transporter-1 deficiency (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 357 total — 10 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 11.7% of screened cell lines
• MANE Select transcript: NM_003051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10922
Approved symbol	SLC16A1
Name	solute carrier family 16 member 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MCT, MCT1
Ensembl gene	ENSG00000155380
Ensembl biotype	protein_coding
OMIM	600682
Entrez	6566

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000369626, ENST00000429288, ENST00000443580, ENST00000458229, ENST00000478835, ENST00000481750, ENST00000538576, ENST00000679803, ENST00000679846, ENST00000863822, ENST00000863823, ENST00000863824, ENST00000863825, ENST00000863826, ENST00000863827, ENST00000863828, ENST00000863829, ENST00000913229, ENST00000913230, ENST00000913231, ENST00000913232, ENST00000948743

RefSeq mRNA: 2 — MANE Select: NM_003051 NM_001166496, NM_003051

CCDS: CCDS858

Canonical transcript exons

ENST00000369626 — 5 exons

Exon	Start	End
ENSE00001159577	112917178	112918044
ENSE00001159586	112921990	112922133
ENSE00001450463	112911847	112914165
ENSE00001450464	112929092	112929352
ENSE00001450465	112956035	112956196

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.4639 / max 855.0917, expressed in 1805 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13895	63.4432	1800
13896	0.7883	471
13894	0.6349	218
13893	0.4204	208
13892	0.1771	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.19	gold quality
ventricular zone	UBERON:0003053	95.04	gold quality
adrenal tissue	UBERON:0018303	94.86	gold quality
smooth muscle tissue	UBERON:0001135	94.72	gold quality
heart left ventricle	UBERON:0002084	94.24	gold quality
endometrium	UBERON:0001295	94.03	gold quality
rectum	UBERON:0001052	93.39	gold quality
placenta	UBERON:0001987	93.32	gold quality
duodenum	UBERON:0002114	93.08	gold quality
muscle tissue	UBERON:0002385	92.89	gold quality
skeletal muscle tissue	UBERON:0001134	92.51	gold quality
heart	UBERON:0000948	91.83	gold quality
transverse colon	UBERON:0001157	91.74	gold quality
right atrium auricular region	UBERON:0006631	91.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.45	gold quality
muscle of leg	UBERON:0001383	91.11	gold quality
stromal cell of endometrium	CL:0002255	91.06	gold quality
colon	UBERON:0001155	91.03	gold quality
myometrium	UBERON:0001296	90.82	gold quality
gastrocnemius	UBERON:0001388	90.81	gold quality
corpus callosum	UBERON:0002336	90.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.52	gold quality
liver	UBERON:0002107	89.79	gold quality
ganglionic eminence	UBERON:0004023	89.26	gold quality
apex of heart	UBERON:0002098	89.19	gold quality
Ammon’s horn	UBERON:0001954	88.77	gold quality
body of uterus	UBERON:0009853	88.60	gold quality
colonic epithelium	UBERON:0000397	88.42	gold quality
right lobe of liver	UBERON:0001114	88.41	gold quality
intestine	UBERON:0000160	88.39	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	3773.15
E-GEOD-124472	yes	591.70
E-GEOD-93593	yes	16.38
E-MTAB-8271	yes	7.37
E-ANND-3	yes	5.06
E-MTAB-6819	no	1156.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, NFKB, PPARA, TFAP2A, TP53, USF1, USF2

miRNA regulators (miRDB)

140 targeting SLC16A1, 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-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• substrate-induced regulation of human colonic MCT1. The basis of this regulation is a butyrate-induced increase in mRNA abundance, resulting from the dual control of gene transcription and stability of the transcript (PMID:11882670)
• the structural organization of the human MCT1 gene and 5’-flanking region which contains potential binding sites for a variety of transcription factors with known association with butyrate’s action in the colon (PMID:11944921)
• Carcinoma samples displaying reduced levels of MCT1 were found to express the high affinity glucose transporter, GLUT1, suggesting that there is a switch from butyrate to glucose as an energy source in colonic epithelia during transition to malignancy (PMID:11953883)
• MCT1 and NHE1 genes play important regulation roles in proliferation and growth of tumor cells, probably by affecting pHi. (PMID:12479094)
• MCT1 is involved in cellular transportation of butyrate, which induces cellular differentiation. Down-regulation is suggested to be involved in human breast cancers. (PMID:12759536)
• MCT mediates biotin uptake in human lymphoid cells. (PMID:12949353)
• MCT1 content in skeletal muscle in Type 2 diabetes is lower compared with healthy men. Strength training increases MCT1 content in healthy men and in Type 2, thus normalizing the content in Type 2. (PMID:14724187)
• studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both monocarboxylate transporter MCT1 and MCT4 activity and expression (PMID:15135232)
• These results show the importance of MCT1 to the ability of butyrate to induce cell-cycle arrest and differentiation, and suggest fundamental differences in the mechanisms by which butyrate modulates specific aspects of cell function. (PMID:15765403)
• MCT1 is functionally active and is the only MCT isoform involved in the apical uptake of monocarboxylates by retinal pigmented epithelial ARPE-19 cells (PMID:15804185)
• Distinct MCT isoforms may be involved in short-chain fatty acid transport across the apical or basolateral membranes in polarized colonic epithelial cells. (PMID:15901598)
• MCT1 gene plays an important role in pHi regulation, lactate transport and cell growth in tumor cells. (PMID:16136905)
• studies demonstrate inhibition of MCT1-mediated butyrate uptake in Caco-2 cells in response to enteropathogenic Escherichia coli infection (PMID:16150873)
• The inhibition of MCT1 during T lymphocyte activation results in selective and profound inhibition of the extremely rapid phase of T cell division essential for an effective immune response. (PMID:16370372)
• Monocarboxylate transporter MCT1 is strongly expressed by glial cells often associated with blood vessels that were identified as astrocytes. (Monocarboxylate transporter MCT1) (PMID:16403470)
• this study shows conflicting adaptations in MCT1 and MCT4 protein and mRNA levels following training, which may indicate post-transcriptional regulation of MCT expression in human muscle. (PMID:16408234)
• demonstrated greater activity of the RBC monocarboxylate cotransporter MCT-1, lower RBC deformability and impaired hematological indices in sickle cell trait (SCT) carriers compared to control subjects (PMID:16441976)
• Targeting the Map kinase signal transduction cascademay provide a potential therapeutic approach in lymphomas and related malignancies that exhibit high levels of the MCT-1 protein. (PMID:17016429)
• A single bout of high-intensity exercise decreased both MCT relative abundance (MCT1 and MCT4) in membrane preparations. (PMID:17082373)
• DL-2-Hydroxy-(4-methylthio)butanoic acid is transported into the colonic cancer cell line cell membrane by a transport mechanissm involving MCT1. (PMID:17182800)
• These studies show that promoter-activating mutations in exercise-induced hyperinsulinism induce SLC16A1 expression in beta cells, permitting pyruvate uptake and pyruvate-stimulated insulin release despite ensuing hypoglycemia. (PMID:17701893)
• In obesity, MCT1 expression appears linked both to changes in oxidative parameters and to changes in visceral adipose tissue content. (PMID:18079261)
• Expression of MCT1 and MCT4 showed a significant gain in plasma membranes of colorectal neoplasms. (PMID:18188595)
• the effective movement of H(+) into the bulk cytosol is increased by CAII, thus slowing the dissipation of the H(+) gradient across the cell membrane, which drives MCT1 activity (PMID:18539591)
• Report effects of high-intensity training on muscle MCT1/4 and postexercise recovery of muscle lactate and hydrogen ions in women. (PMID:18832090)
• PKC-zeta dependent stimulation of the human MCT1 promoter involves transcription factor AP2. (PMID:19033536)
• MCT1 was found to be expressed by an array of primary human tumors, we suggest that MCT1 inhibition has clinical antitumor potential. (PMID:19033663)
• miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. (PMID:19427019)
• carriers of the A1470T polymorphism in the MTC1 (monocarboxylate transporter 1) gene exhibit a worse lactate transport capability (PMID:19850519)
• Data suggest that hypoxia increases lactate release from adipocytes and modulates MCT expression in a type-specific manner, with MCT1 and MCT4, but not MCT2 expression, being hypoxia-inducible transcription factor-1 (HIF-1) dependent. (PMID:19876643)
• the -363-855T>C is a novel mutation. The 1282G>A (Val(428)Ile) is a novel SNP and was found as heterozygotic in 4 subjects. The 1470T>A (Asp(490)Glu) was found to be a common polymorphism in this study. (PMID:19881260)
• close correlation between the Ca2+ level and pH(in), and NHEs were involved with the MCT mediated uptake process (PMID:19905008)
• Monocarboxylic acid transporter 1 was expressed in the human corneal epithelium at mRNA and protein levels. (PMID:20035863)
• MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44, were analysed. (PMID:20454640)
• Increased MCT1 association with CD147 at the apical membrane in response to somatostatin (SST) is p38 MAP kinase dependent and underlies the stimulatory effects of SST on butyrate uptake in human intestinal epithelial cells. (PMID:20501436)
• results provide evidence for a prognostic value of MCT1 in breast carcinoma (PMID:20636790)
• Loss of MCT1 on brain microvessels is mechanistically involved in the pathophysiology of drug-resistant temporal lobe epilepsy; re-expression of MCT1 may represent a novel therapeutic approach for this disease. (PMID:21081165)
• We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness (PMID:21306479)
• miR-29a, miR-29b selectively target MCT1 3’UTR ; the miR-29 isoforms are highly expressed in islets and contribute to silencing Mct1 in beta cells; miR-29 isoforms contribute to beta-cell-specific silencing of the MCT1 transporter and may affect insulin release (PMID:21646425)
• Data show that a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. (PMID:21787388)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc16a1a	ENSDARG00000016963
danio_rerio	slc16a1b	ENSDARG00000068572
mus_musculus	Slc16a1	ENSMUSG00000032902
rattus_norvegicus	Slc16a1	ENSRNOG00000019996
drosophila_melanogaster	Mct1	FBGN0023549
drosophila_melanogaster	CG14196	FBGN0031002
drosophila_melanogaster	CG8051	FBGN0031012
drosophila_melanogaster	Sln	FBGN0033657
drosophila_melanogaster	CG8468	FBGN0033913
drosophila_melanogaster	Targ	FBGN0033955
drosophila_melanogaster	CG13907	FBGN0035173
drosophila_melanogaster	out	FBGN0259834
caenorhabditis_elegans		WBGENE00003986
caenorhabditis_elegans		WBGENE00010834
caenorhabditis_elegans		WBGENE00015273
caenorhabditis_elegans		WBGENE00015676
caenorhabditis_elegans		WBGENE00020168
caenorhabditis_elegans		WBGENE00021227

Paralogs (13): SLC16A8 (ENSG00000100156), SLC16A6 (ENSG00000108932), SLC16A10 (ENSG00000112394), SLC16A7 (ENSG00000118596), SLC16A3 (ENSG00000141526), SLC16A2 (ENSG00000147100), SLC16A12 (ENSG00000152779), SLC16A14 (ENSG00000163053), SLC16A9 (ENSG00000165449), SLC16A4 (ENSG00000168679), SLC16A5 (ENSG00000170190), SLC16A11 (ENSG00000174326), SLC16A13 (ENSG00000174327)

Protein

Protein identifiers

Monocarboxylate transporter 1 — P53985 (reviewed: P53985)

Alternative names: Solute carrier family 16 member 1

All UniProt accessions (4): P53985, Q5T8R3, Q5T8R4, Q5T8R5

UniProt curated annotations — full annotation on UniProt →

Function. Bidirectional proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH. The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis. Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart. Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition.

Subunit / interactions. Interacts with EMB; interaction mediates SLC16A1 targeting to the plasma membrane. Interacts with isoform 2 of BSG; interaction mediates SLC16A1 targeting to the plasma membrane.

Subcellular location. Cell membrane. Basolateral cell membrane. Apical cell membrane.

Tissue specificity. Widely expressed. Detected in heart and in blood lymphocytes and monocytes (at protein level).

Disease relevance. Symptomatic deficiency in lactate transport (SDLT) [MIM:245340] Deficiency of lactate transporter may result in an acidic intracellular environment created by muscle activity with consequent degeneration of muscle and release of myoglobin and creatine kinase. This defect might compromise extreme performance in otherwise healthy individuals. The disease is caused by variants affecting the gene represented in this entry. Hyperinsulinemic hypoglycemia, familial, 7 (HHF7) [MIM:610021] A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF7 features include exercise-induced hyperinsulinism, loss of consciousness due to hypoglycemia, and hypoglycemic seizures. HHF7 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Monocarboxylate transporter 1 deficiency (MCT1D) [MIM:616095] A metabolic disorder characterized by recurrent ketoacidosis, a pathologic state due to ketone formation exceeding ketone utilization. The clinical consequences of ketoacidosis are vomiting, osmotic diuresis, dehydration, and Kussmaul breathing. The condition may progress to decreased consciousness and, ultimately, death. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Selectively inhibited by AZD3965, that acts as a competitive inhibitor binding to the central channel in the outward open conformation.

Miscellaneous. Overexpression in pancreatic beta-cells triggers insulin secretion in response to pyruvate, causing hyperinsulemia and hypoglycemia during strenuous exercise.

Similarity. Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P53985-1	1	yes
P53985-2	2

RefSeq proteins (2): NP_001159968, NP_003042* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004743	MCT	Family
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050327	Proton-linked_MCT	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 8 shown:

• succinate(in) + 2 H(+)(in) = succinate(out) + 2 H(+)(out) (RHEA:29303)
• (S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out) (RHEA:29415)
• pyruvate(out) + H(+)(out) = pyruvate(in) + H(+)(in) (RHEA:64720)
• acetoacetate(out) + H(+)(out) = acetoacetate(in) + H(+)(in) (RHEA:71775)
• 4-methyl-2-oxopentanoate(out) + H(+)(out) = 4-methyl-2-oxopentanoate(in) + H(+)(in) (RHEA:71779)
• 3-methyl-2-oxobutanoate(out) + H(+)(out) = 3-methyl-2-oxobutanoate(in) + H(+)(in) (RHEA:71783)
• (R)-3-hydroxybutanoate(out) + H(+)(out) = (R)-3-hydroxybutanoate(in) + H(+)(in) (RHEA:71795)
• acetate(out) + H(+)(out) = acetate(in) + H(+)(in) (RHEA:71803)

UniProt features (88 total): helix 19, mutagenesis site 16, topological domain 13, transmembrane region 12, modified residue 8, sequence variant 5, strand 4, binding site 3, compositionally biased region 2, turn 2, chain 1, region of interest 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7CKO	ELECTRON MICROSCOPY	2.95
7CKR	ELECTRON MICROSCOPY	3
6LYY	ELECTRON MICROSCOPY	3.2
6LZ0	ELECTRON MICROSCOPY	3.3
7DA5	ELECTRON MICROSCOPY	3.3
7YR5	ELECTRON MICROSCOPY	3.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53985-F1	83.28	0.68

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 (3): 38; 309; 313

Post-translational modifications (8): 210, 213, 231, 461, 466, 467, 483, 498

Mutagenesis-validated functional residues (16):

Position	Phenotype
34	reduces lactate transmembrane transporter activity.
38	complete loss of transport lactate transmembrane transporter activity.
70	abolishes binding with azd3965.
143	does not affect plasma membrane localization.
143	abolishes lactate transmembrane transporter activity. reduces plasma membrane localization.
151	azd3965 inhibition is reduced by approximately 2 folds. the affinity for azd3965 is decreased by 10 folds.
153	abolishes lactate transmembrane transporter activity. abolishes expression at the cell membrane.
187	decreases interaction with bsn isoform 2.
281	azd3965 does not inhibit lactate transmembrane transporter activity. the affinity for azd3965 is reduced by 55 folds.
309	abolishes binding with azd3965.
309	complete loss of lactate transmembrane transporter activity.
313	abolishes binding with azd3965.
367	reduces lactate transmembrane transporter activity.
367	abolishes lactate transmembrane transporter activity.
371	reduces lactate transmembrane transporter activity by 50%.
371	azd3965 inhibition is reduced by approximately 2 folds. the affinity for azd3965 is decreased by 10 folds.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-433692	Proton-coupled monocarboxylate transport
R-HSA-5619070	Defective SLC16A1 causes symptomatic deficiency in lactate transport (SDLT)
R-HSA-9749641	Aspirin ADME
R-HSA-109582	Hemostasis
R-HSA-1643685	Disease
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-9748784	Drug ADME

MSigDB gene sets: 457 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WWTAAGGC_UNKNOWN, GOBP_BEHAVIOR, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_RESPONSE_TO_FOOD, GOBP_HORMONE_TRANSPORT, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS

GO Biological Process (17): lipid metabolic process (GO:0006629), centrosome cycle (GO:0007098), monocarboxylic acid transport (GO:0015718), mevalonate transport (GO:0015728), response to food (GO:0032094), plasma membrane lactate transport (GO:0035879), glucose homeostasis (GO:0042593), pyruvate catabolic process (GO:0042867), regulation of insulin secretion (GO:0050796), behavioral response to nutrient (GO:0051780), succinate transmembrane transport (GO:0071422), transport across blood-brain barrier (GO:0150104), pyruvate transmembrane transport (GO:1901475), carboxylic acid transmembrane transport (GO:1905039), lactate transmembrane transport (GO:0035873), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (12): monocarboxylic acid transmembrane transporter activity (GO:0008028), lactate transmembrane transporter activity (GO:0015129), mevalonate transmembrane transporter activity (GO:0015130), succinate transmembrane transporter activity (GO:0015141), lactate:proton symporter activity (GO:0015650), identical protein binding (GO:0042802), carboxylic acid transmembrane transporter activity (GO:0046943), protein binding (GO:0005515), symporter activity (GO:0015293), solute:proton symporter activity (GO:0015295), secondary active monocarboxylate transmembrane transporter activity (GO:0015355), transmembrane transporter activity (GO:0022857)

GO Cellular Component (10): centrosome (GO:0005813), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), cell junction (GO:0030054), synapse (GO:0045202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of organic anions	1
SLC transporter disorders	1
Drug ADME	1
Hemostasis	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
carboxylic acid transmembrane transport	4
plasma membrane region	3
cellular anatomical structure	3
carboxylic acid transport	2
monocarboxylic acid transport	2
lactate transmembrane transport	2
transmembrane transport	2
carboxylic acid transmembrane transporter activity	2
monocarboxylic acid transmembrane transporter activity	2
secondary active transmembrane transporter activity	2
primary metabolic process	1
cell cycle process	1
microtubule organizing center organization	1
organic hydroxy compound transport	1
response to nutrient levels	1
response to chemical	1
carbohydrate homeostasis	1
pyruvate metabolic process	1
monocarboxylic acid catabolic process	1
insulin secretion	1
regulation of protein secretion	1
regulation of peptide hormone secretion	1
response to nutrient	1
behavior	1
succinate transport	1
vascular transport	1
pyruvate transport	1
lactate transport	1
transport	1
cellular process	1
monoatomic cation transmembrane transport	1
mevalonate transport	1
C4-dicarboxylate transmembrane transporter activity	1
succinate transmembrane transport	1
lactate transmembrane transporter activity	1
solute:proton symporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
protein binding	1
transmembrane transporter activity	1
binding	1

Protein interactions and networks

STRING

1772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC16A1	BSG	P35613	983
SLC16A1	SLC18B1	Q6NT16	831
SLC16A1	SLC18A1	P54219	777
SLC16A1	CA2	P00918	751
SLC16A1	KCNJ11	Q14654	746
SLC16A1	SLC5A8	Q8N695	733
SLC16A1	GCK	P35557	706
SLC16A1	SLC17A1	Q14916	684
SLC16A1	LDHA	P00338	683
SLC16A1	SLC2A1	P11166	660
SLC16A1	INS	P01308	626
SLC16A1	ABCC8	Q09428	616
SLC16A1	EMB	Q6PCB8	591
SLC16A1	SLC5A12	Q1EHB4	582
SLC16A1	HCAR2	Q8TDS4	549

IntAct

243 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	DDX3X	psi-mi:“MI:0914”(association)	0.630
SLC16A1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.590
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC16A1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	SLC16A1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
CARD11	SLC16A1	psi-mi:“MI:0407”(direct interaction)	0.440
SLC16A1	CASK	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (281): SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-RNA), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS), SLC16A1 (Affinity Capture-MS)

ESM2 similar proteins: A1L1W9, A1L272, A2SWM2, A8WGF7, D3Z5L6, D4A9K4, F4IKF6, G5E8K6, G8XYX6, O15374, O35440, O70324, O70451, O70594, P30638, P36021, P53985, P53986, P53987, P53988, P57057, P58355, Q00910, Q03064, Q0VA82, Q3MHW6, Q3U9N9, Q569T7, Q5M7K3, Q5U3U7, Q5XGK0, Q63344, Q640L2, Q6DCX5, Q6GPQ3, Q6NMN6, Q6NT16, Q6NUB3, Q7ZWG6, Q8AVC3

Diamond homologs: A0LNN5, B1AT66, I1RV24, O15375, O15403, O15427, O35440, O35910, O60669, O70451, O95907, P53985, P53986, P53987, P53988, P57787, P57788, Q03064, Q17QR6, Q3MHW6, Q63344, Q66HE2, Q7RTY0, Q7TMR7, Q8CE94, Q90632, D4A734, G5E8K6, O15374, O35308, O70461, Q503M4, Q5NC32, Q6GM59, Q6P2X9, Q6ZSM3, Q8BGC3, Q8NCK7, Q8R0M8, M0RCI4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	8	35.4×	8e-09
Assembly and cell surface presentation of NMDA receptors	12	23.6×	4e-11
VEGFR2 mediated cell proliferation	5	22.1×	2e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	21.1×	2e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	21.1×	2e-04
Dopamine Neurotransmitter Release Cycle	5	19.2×	3e-04
Long-term potentiation	5	18.4×	4e-04
Neurexins and neuroligins	10	15.3×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	35.2×	1e-10
regulation of long-term neuronal synaptic plasticity	5	30.0×	1e-04
receptor clustering	6	22.7×	7e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	7	21.0×	1e-05
Rho protein signal transduction	6	9.0×	7e-03
exocytosis	8	7.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	10
Uncertain significance	198
Likely benign	100
Benign	11

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
158079	NM_003051.4(SLC16A1):c.937C>T (p.Arg313Ter)	Pathogenic
158081	NM_003051.4(SLC16A1):c.586C>T (p.Arg196Ter)	Pathogenic
160370	NM_003051.4(SLC16A1):c.982C>T (p.Arg328Ter)	Pathogenic
2077604	NM_003051.4(SLC16A1):c.427C>T (p.Arg143Ter)	Pathogenic
2637719	NM_003051.4(SLC16A1):c.339C>A (p.Tyr113Ter)	Pathogenic
2691470	NM_003051.4(SLC16A1):c.719_720del (p.Gln240fs)	Pathogenic
2717650	NM_003051.4(SLC16A1):c.672dup (p.Asp225fs)	Pathogenic
3242581	NM_003051.4(SLC16A1):c.202dup (p.Val68fs)	Pathogenic
450708	NM_003051.3(SLC16A1):c.218delG	Pathogenic
800884	NM_003051.4(SLC16A1):c.1079del (p.Ala360fs)	Pathogenic
1325075	NM_003051.4(SLC16A1):c.727C>T (p.Arg243Ter)	Likely pathogenic
160372	NM_003051.4(SLC16A1):c.490dup (p.Leu164fs)	Likely pathogenic
2584348	NM_003051.4(SLC16A1):c.41del (p.Pro14fs)	Likely pathogenic
2687852	NM_003051.4(SLC16A1):c.97T>N (p.Ser33Xaa)	Likely pathogenic
3361937	NM_003051.4(SLC16A1):c.764T>G (p.Leu255Ter)	Likely pathogenic
3362614	NM_003051.4(SLC16A1):c.97del (p.Ser33fs)	Likely pathogenic
3899393	NM_003051.4(SLC16A1):c.74G>T (p.Gly25Val)	Likely pathogenic
3899396	NM_003051.4(SLC16A1):c.1207C>T (p.Leu403Phe)	Likely pathogenic
4526516	NM_003051.4(SLC16A1):c.1153C>T (p.Gln385Ter)	Likely pathogenic
827804	NM_003051.4(SLC16A1):c.328C>T (p.Gln110Ter)	Likely pathogenic

SpliceAI

1151 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112918045:C:CA	acceptor_loss	1.0000
1:112921985:CTCA:C	donor_loss	1.0000
1:112921986:TCACC:T	donor_loss	1.0000
1:112921987:CA:C	donor_loss	1.0000
1:112921988:A:AC	donor_gain	1.0000
1:112921988:ACCT:A	donor_gain	1.0000
1:112921989:C:CC	donor_gain	1.0000
1:112921989:CCT:C	donor_gain	1.0000
1:112921989:CCTC:C	donor_gain	1.0000
1:112922130:GGAC:G	acceptor_gain	1.0000
1:112922134:C:CC	acceptor_gain	1.0000
1:112929086:ACTT:A	donor_loss	1.0000
1:112929087:CTT:C	donor_loss	1.0000
1:112929088:TTA:T	donor_loss	1.0000
1:112929089:TACCT:T	donor_loss	1.0000
1:112929090:A:T	donor_loss	1.0000
1:112929091:C:CG	donor_loss	1.0000
1:112929350:TAT:T	acceptor_gain	1.0000
1:112929352:TCT:T	acceptor_loss	1.0000
1:112929353:C:T	acceptor_loss	1.0000
1:112929354:T:G	acceptor_loss	1.0000
1:112914172:A:C	acceptor_gain	0.9900
1:112918040:AAGAC:A	acceptor_gain	0.9900
1:112918041:AGAC:A	acceptor_gain	0.9900
1:112918042:GAC:G	acceptor_gain	0.9900
1:112918045:C:CC	acceptor_gain	0.9900
1:112918046:T:A	acceptor_loss	0.9900
1:112922131:GAC:G	acceptor_gain	0.9900
1:112923370:TCCA:T	donor_gain	0.9900
1:112929090:A:AC	donor_gain	0.9900

AlphaMissense

3248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112917315:C:T	G364E	0.999
1:112917944:G:C	S154R	0.999
1:112917944:G:T	S154R	0.999
1:112917946:T:G	S154R	0.999
1:112917231:C:T	G392E	0.998
1:112917232:C:G	G392R	0.998
1:112917232:C:T	G392R	0.998
1:112917303:C:T	G368E	0.998
1:112917304:C:A	G368W	0.998
1:112917481:C:G	D309H	0.998
1:112917989:G:C	F139L	0.998
1:112917989:G:T	F139L	0.998
1:112917991:A:G	F139L	0.998
1:112918038:C:T	G123E	0.998
1:112922123:G:C	S76R	0.998
1:112922123:G:T	S76R	0.998
1:112922125:T:G	S76R	0.998
1:112929217:C:T	G31D	0.998
1:112917198:A:T	L403H	0.997
1:112917211:A:G	C399R	0.997
1:112917245:G:C	F387L	0.997
1:112917245:G:T	F387L	0.997
1:112917247:A:G	F387L	0.997
1:112917281:A:C	F375L	0.997
1:112917281:A:T	F375L	0.997
1:112917283:A:G	F375L	0.997
1:112917316:C:G	G364R	0.997
1:112917316:C:T	G364R	0.997
1:112917384:C:T	G341E	0.997
1:112917480:T:A	D309V	0.997

dbSNP variants (sampled 300 via entrez): RS1000006233 (1:112956002 G>C), RS1000076080 (1:112935788 A>G), RS1000126291 (1:112948237 A>G), RS1000131883 (1:112929643 T>C), RS1000209423 (1:112911634 A>G), RS1000276960 (1:112946341 G>A,C), RS1000318936 (1:112929646 G>A), RS1000358764 (1:112912032 G>A), RS1000391124 (1:112948036 T>C), RS1000546889 (1:112913254 A>G), RS1000644705 (1:112941121 C>T), RS1000673915 (1:112952991 C>CA), RS1000725363 (1:112946310 A>G), RS1000747504 (1:112952863 T>C), RS1000808169 (1:112912974 A>C,G)

Disease associations

OMIM: gene MIM:600682 | disease phenotypes: MIM:245340, MIM:610021, MIM:616095

GenCC curated gene-disease

Disease	Classification	Inheritance
ketoacidosis due to monocarboxylate transporter-1 deficiency	Definitive	Autosomal recessive
exercise-induced hyperinsulinism	Strong	Autosomal dominant
disorder of fatty acid and ketone body metabolism	Limited	Autosomal dominant
metabolic myopathy due to lactate transporter defect	Limited	Unknown

Mondo (4): metabolic myopathy due to lactate transporter defect (MONDO:0009501), exercise-induced hyperinsulinism (MONDO:0012396), ketoacidosis due to monocarboxylate transporter-1 deficiency (MONDO:0014490), disorder of fatty acid and ketone body metabolism (MONDO:0019223)

Orphanet (3): Exercise-induced hyperinsulinism (Orphanet:165991), Metabolic myopathy due to lactate transporter defect (Orphanet:171690), Ketoacidosis due to monocarboxylate transporter-1 deficiency (Orphanet:438075)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000842	Hyperinsulinemia
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001943	Hypoglycemia
HP:0001993	Ketoacidosis
HP:0002173	Hypoglycemic seizures
HP:0002919	Ketonuria
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003457	EMG abnormality
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003710	Exercise-induced muscle cramps
HP:0004510	Pancreatic islet-cell hyperplasia
HP:0008967	Exercise-induced muscle stiffness
HP:0009020	Exercise-induced muscle fatigue
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0012734	Ketotic hypoglycemia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006976_34	Macular thickness	5.000000e-18
GCST010002_392	Refractive error	8.000000e-20
GCST010916_4	Proportion of activated microglia (inferior temporal cortex)	2.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C565449	Erythrocyte Lactate Transporter Defect (supp.)
C538376	Hyperinsulinemic hypoglycemia, familial, 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4360 (SINGLE PROTEIN), CHEMBL4802067 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 24,844 (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
CHEMBL1399124	SYROSINGOPINE	2	1,162
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL3335793	AZD3965	1	159

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7169	SLC16A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC16 family of monocarboxylate transporters

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

Ligand	Action	Affinity	Parameter
AZD3965	Inhibition	8.49	pKi
compound 30 [PMID: 16455256]	Inhibition	8.32	pKi
BAY-8002	Inhibitor	8.3	pKi

Binding affinities (BindingDB)

279 measured of 280 human assays (280 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.09 nM
7-[(3-hydroxypropyl)sulfanyl]-2-methyl-4-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,6-dihydro-1H-pyrrolo[3,4-d]pyridazin-1-one	KI	0.1 nM
5-[(3-hydroxypropyl)sulfanyl]-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.28 nM
5-{[(1R,3R)-3-hydroxycyclopentyl]sulfanyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.29 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-yloxy)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.31 nM
5-[(3-hydroxypropyl)sulfanyl]-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione	KI	0.33 nM
5-[(3-hydroxypropyl)sulfanyl]-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.35 nM
5-{[(1R,3S)-3-hydroxycyclopentyl]sulfanyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.42 nM
5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-{1H-pyrrolo[2,3-b]pyridin-3-ylmethyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.43 nM
5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.52 nM
5-{[(1S,3R,4S)-3,4-dihydroxycyclopentyl]sulfanyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.68 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-6-(1H-indol-3-ylmethyl)-3-methyl-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.79 nM
6-[(6-fluoroquinolin-4-yl)methyl]-5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	0.81 nM
5-{[(3R)-3-hydroxypyrrolidine-1-]sulfonyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	1.1 nM
6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	1.2 nM
5-{[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]carbonyl}-3-methyl-6-{[2-(methylamino)-1H-1,3-benzodiazol-1-yl]methyl}-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	1.7 nM
3-methyl-1-(2-methylpropyl)-5-(propan-2-ylsulfanyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	2.2 nM
5-{[(1R,2R)-2-hydroxycyclopentyl]sulfanyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	2.7 nM
6-[(4,5-dichloro-2-methyl-1H-imidazol-1-yl)methyl]-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxo-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-5-carboxamide	KI	3.2 nM
5-(cyclopentylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	3.2 nM
5-[(3-hydroxy-3-methylazetidin-1-yl)carbonyl]-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	3.5 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-6-(isoquinolin-4-ylmethyl)-3-methyl-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	3.9 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-{1H-pyrrolo[2,3-b]pyridin-3-ylmethyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	4.7 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione	KI	4.8 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	4.9 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-(quinolin-5-ylmethyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	5.3 nM
3-methyl-1-(2-methylpropyl)-5-(pyrrolidin-1-ylcarbonyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	5.5 nM
5-(ethylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	6 nM
5-(cyclohexylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	6 nM
5-[(2,3-dihydroxypropyl)sulfanyl]-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	6.5 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-6-{[2-(methylamino)-1H-1,3-benzodiazol-1-yl]methyl}-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	6.6 nM
3-methyl-1-(2-methylpropyl)-5-(piperidin-1-ylcarbonyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	8.7 nM
5-(azetidin-1-ylcarbonyl)-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	9.2 nM
5-{[(1R,3S)-3-hydroxycyclopentane]sulfonyl}-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	12 nM
5-(cyclobutylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	13 nM
5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-6-[(2-methyl-1H-1,3-benzodiazol-1-yl)methyl]-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	16 nM
6-[(4,5-dichloro-2-methyl-1H-imidazol-1-yl)methyl]-5-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	26 nM
5-{[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]carbonyl}-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	29 nM
N,N,3-trimethyl-1-(2-methylpropyl)-2,4-dioxo-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-5-carboxamide	KI	37 nM
2-[[1-[(2-Chlorophenyl)methyl]-5-[3- (cyclopropylmethoxy)phenyl]pyrazol-3- yl]methoxy]-2-methyl-propanoic acid. 1HNMR (CDCl3): δ 0.25-0.29 (m, 2H), 0.58-0.63 (m, 2H), 14.16-1.20 (m, 1H), 1.55 (s, 6H), 5.58 (d, 2H), 4.63 (s, 2H), 5.42 (s, 2H), 6.40 (s, 1H), 6.374-6.78 (m, 2H), 6.84-6.93 (m, 2H), 7.18-7.28 (m, 3H), 7.33-7.35 (m, 1H).	IC50	54.5 nM	US-10202350: MCT4 inhibitors for treating disease
2-[[1-[(2-chlorophenyl)methyl]-5-(4-cyclopropyloxythiophen-2-yl)pyrrol-3-yl]methoxy]-2-methylpropanoic acid	IC50	55 nM	US-10214492
5-(azetidin-1-ylcarbonyl)-3-methyl-6-{[2-(methylamino)-1H-1,3-benzodiazol-1-yl]methyl}-1-(2-methylpropyl)-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-2,4-dione	KI	59 nM
1-[[5-(4-Chlorophenyl)-1-[(2- chlorophenyl)methyl]pyrazol-3- yl]methoxy]cyclopropanecarboxylic acid 1H NMR (CD3OD, 400 MHz) δ 1.18- 1.32 (m, 3H), 1.64-1.80 (m, 1H), 4.61 (s, 2H), 5.42 (s, 2H), 6.52 (s, 1H), 6.60-6.80 (m, 1H), 7.20-52 (m, 7H).	IC50	100 nM	US-10202350: MCT4 inhibitors for treating disease
1-[[1-[(2-Chlorophenyl)methyl]-5-(3- methoxyphenyl)pyrazol-3- yl]methoxy]cyclobutanecarboxylic acid. 1HNMR (CDCl3): δ 1.78-1.85 (m 1H), 1.95-2.04 (m, 2H), 2.18-2.25 (m, 1H), 3.09-3.14 (m, 1H), 3.66 (s, 3H), 4.27-4.32 (m, 1H), 4.55-4.65 (dd, 2H), 5.43 (s, 2H), 6.44 (s, 1H), 6.73-6.91 (m, 4H), 7.17-7.34 (m 4).	IC50	100 nM	US-10202350: MCT4 inhibitors for treating disease
2-[[1-[[3-(dimethylamino)phenyl]methyl]-5-[3-(2-methylpropoxy)phenyl]pyrazol-3-yl]methoxy]-2-methylpropanoic acid	IC50	102 nM	US-10214492
2-[[1-[(2-ethoxyphenyl)methyl]-5-(1-methylindazol-6-yl)pyrazol-3-yl]methoxy]-2-methylpropanoic acid	IC50	102 nM	US-10214492
2-[[1-[(2-chlorophenyl)methyl]-5-[2-(2-methylpropoxy)-1,3-thiazol-5-yl]pyrazol-3-yl]methoxy]-2-methylpropanoic acid	IC50	104 nM	US-10214492
N,N,3-trimethyl-2,4-dioxo-1-(propan-2-yl)-6-{[2-(trifluoromethyl)phenyl]methyl}-1H,2H,3H,4H-thieno[2,3-d]pyrimidine-5-carboxamide	KI	117 nM
(E)-4-[1-[(2-chlorophenyl)methyl]-5-(3-methoxyphenyl)pyrazol-3-yl]-2,2-dimethylbut-3-enoic acid	IC50	152 nM	US-10214492
2-[[5-(3-cyclobutyloxyphenyl)-1-[(2-ethoxyphenyl)methyl]pyrazol-3-yl]methoxy]-2-methylpropanoic acid	IC50	154 nM	US-10214492

ChEMBL bioactivities

200 potent at pChembl≥5 of 572 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	Ki	0.08	nM	CHEMBL205526
10.05	Ki	0.09	nM	CHEMBL218573
10.02	Ki	0.095	nM	CHEMBL380192
10.02	Ki	0.0955	nM	CHEMBL380192
10.00	Ki	0.1	nM	CHEMBL380192
9.80	EC50	0.16	nM	CHEMBL3818777
9.56	Ki	0.2754	nM	CHEMBL205526
9.55	Ki	0.28	nM	CHEMBL205526
9.54	Ki	0.29	nM	CHEMBL379682
9.52	Ki	0.302	nM	CHEMBL205526
9.51	Ki	0.31	nM	CHEMBL219098
9.48	Ki	0.33	nM	CHEMBL85752
9.48	Ki	0.33	nM	CHEMBL205526
9.48	Ki	0.33	nM	CHEMBL5559179
9.48	Ki	0.3311	nM	CHEMBL85752
9.46	Ki	0.35	nM	CHEMBL204887
9.45	Ki	0.3548	nM	CHEMBL204887
9.38	Ki	0.42	nM	CHEMBL205845
9.37	Ki	0.43	nM	CHEMBL384536
9.30	Ki	0.5012	nM	CHEMBL204887
9.28	Ki	0.52	nM	CHEMBL219861
9.17	Ki	0.68	nM	CHEMBL381601
9.15	Ki	0.71	nM	CHEMBL380192
9.15	Ki	0.7079	nM	CHEMBL380192
9.10	EC50	0.8	nM	CHEMBL3818311
9.10	EC50	0.8	nM	CHEMBL3817951
9.10	EC50	0.8	nM	CHEMBL3818150
9.10	Ki	0.79	nM	CHEMBL205807
9.09	Ki	0.81	nM	CHEMBL218468
8.96	Ki	1.1	nM	CHEMBL378405
8.93	Ki	1.175	nM	CHEMBL85752
8.92	Ki	1.2	nM	CHEMBL375166
8.80	Kd	1.6	nM	AZD3965
8.77	Ki	1.7	nM	CHEMBL218628
8.72	Ki	1.9	nM	CHEMBL208487
8.70	Ki	2	nM	AZD3965
8.66	Ki	2.2	nM	CHEMBL206229
8.57	Ki	2.7	nM	CHEMBL204848
8.50	Ki	3.162	nM	CHEMBL205807
8.49	Ki	3.2	nM	CHEMBL383696
8.49	Ki	3.2	nM	CHEMBL387125
8.48	Ki	3.311	nM	CHEMBL205742
8.47	Ki	3.388	nM	CHEMBL1221551
8.46	Ki	3.5	nM	CHEMBL439871
8.41	Ki	3.9	nM	CHEMBL207100
8.40	EC50	4	nM	CHEMBL3818851
8.33	Ki	4.7	nM	CHEMBL205092
8.32	Ki	4.8	nM	CHEMBL205742
8.31	Ki	4.9	nM	CHEMBL208487
8.30	EC50	5	nM	CHEMBL380192

PubChem BioAssay actives

167 with measured affinity, of 240 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
5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0001	uM
5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	263772: Binding affinity to MCT1 by SPA	ki	0.0001	uM
5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)pyrrolo[3,4-d]pyridazin-4-one	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0001	uM
(2S)-2-amino-N-[5-[[4-[[5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-4-oxopyrrolo[3,4-d]pyridazin-6-yl]methyl]isoquinolin-1-yl]amino]pentyl]pentanediamide	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0002	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-naphthalen-1-yloxythieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0003	uM
5-[(1R,3R)-3-hydroxycyclopentyl]sulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0003	uM
5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0003	uM
5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)pyrrolo[3,4-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0003	uM
3-(3-hydroxypropylsulfanyl)-5-methyl-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)thieno[2,3-d]pyridazin-4-one	2074104: Binding affinity to human MCT1 assessed as inhibition constant	ki	0.0003	uM
5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0004	uM
5-[(1R,3S)-3-hydroxycyclopentyl]sulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0004	uM
5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0005	uM
5-[(3S,4R)-3,4-dihydroxycyclopentyl]sulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0007	uM
(2S)-2-amino-N-[5-[[4-[[5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-4-oxopyrrolo[3,4-d]pyridazin-6-yl]methyl]quinolin-2-yl]amino]pentyl]pentanediamide	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0008	uM
6-[[1-(5-aminopentylamino)isoquinolin-4-yl]methyl]-5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)pyrrolo[3,4-d]pyridazin-4-one	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0008	uM
(2S)-2-amino-3-[4-[5-[4-[[5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-4-oxopyrrolo[3,4-d]pyridazin-6-yl]methyl]naphthalen-1-yl]pent-4-ynoxy]phenyl]propanoic acid	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0008	uM
6-[(6-fluoroquinolin-4-yl)methyl]-5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0008	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-6-(1H-indol-3-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0008	uM
5-[(3R)-3-hydroxypyrrolidin-1-yl]sulfonyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0011	uM
6-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0012	uM
5-[(4S)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione	1167921: Binding affinity to MCT1 (unknown origin)	kd	0.0016	uM
5-[(4S)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-3-methyl-6-[[2-(methylamino)benzimidazol-1-yl]methyl]-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0017	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	263772: Binding affinity to MCT1 by SPA	ki	0.0019	uM
3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanyl-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0022	uM
5-[(1R,2R)-2-hydroxycyclopentyl]sulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0027	uM
6-[(4,5-dichloro-2-methylimidazol-1-yl)methyl]-N-methoxy-N,3-dimethyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide	1798148: Radioligand Filter Binding Assay from Article 10.1021/jm060995h: “Optimization of monocarboxylate transporter 1 blockers through analysis and modulation of atropisomer interconversion properties.”	ki	0.0032	uM
5-cyclopentylsulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0032	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(quinolin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	503443: Displacement of [3H]5-[(3-hydroxypropyl)thio]-3-methyl-1-[2-(methyl-t)propyl-2,3-t2]-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione from human MCT1 expressed in INS1 cell membrane	ki	0.0033	uM
5-(2,5-dihydropyrrole-1-carbonyl)-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	503442: Displacement of [3H]5-[(3-hydroxypropyl)thio]-3-methyl-1-[2-(methyl-t)propyl-2,3-t2]-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione from MCT1 in human Jurkat cell membranes	ki	0.0034	uM
5-(3-hydroxy-3-methylazetidine-1-carbonyl)-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0035	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-6-(isoquinolin-4-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0039	uM
(2S)-2-amino-N-[5-[4-[[5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-4-oxopyrrolo[3,4-d]pyridazin-6-yl]methyl]naphthalen-1-yl]pent-4-ynyl]pentanediamide	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0040	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0047	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(quinolin-5-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0053	uM
3-methyl-1-(2-methylpropyl)-5-(pyrrolidine-1-carbonyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0055	uM
5-ethylsulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0060	uM
5-cyclohexylsulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0060	uM
5-(2,3-dihydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0065	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-6-[[2-(methylamino)benzimidazol-1-yl]methyl]-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0066	uM
(E)-2-cyano-3-[2-methoxy-4-(N-phenylanilino)phenyl]prop-2-enoic acid	1931139: Inhibition of MCT1 (unknown origin) assessed as reduction in [14C]lactate uptake incubated for 20 mins by liquid scintillation counting analysis	ic50	0.0080	uM
3-methyl-1-(2-methylpropyl)-5-(piperidine-1-carbonyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0087	uM
(E)-2-cyano-3-[4-(dibutylamino)-2-methoxyphenyl]prop-2-enoic acid	1931139: Inhibition of MCT1 (unknown origin) assessed as reduction in [14C]lactate uptake incubated for 20 mins by liquid scintillation counting analysis	ic50	0.0090	uM
5-(azetidine-1-carbonyl)-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0092	uM
6-[(4-bromonaphthalen-1-yl)methyl]-5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)pyrrolo[3,4-d]pyridazin-4-one	1307037: Inhibition of MCT1 in human Raji cells assessed as inhibition of cell proliferation after 96 hrs by MTT assay	ec50	0.0110	uM
(E)-3-[4-[bis(2-methylpropyl)amino]-2-methoxyphenyl]-2-cyanoprop-2-enoic acid	1931139: Inhibition of MCT1 (unknown origin) assessed as reduction in [14C]lactate uptake incubated for 20 mins by liquid scintillation counting analysis	ic50	0.0110	uM
5-[(1R,3S)-3-hydroxycyclopentyl]sulfonyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0120	uM
5-cyclobutylsulfanyl-3-methyl-1-(2-methylpropyl)-6-[[2-(trifluoromethyl)phenyl]methyl]thieno[2,3-d]pyrimidine-2,4-dione	1798149: Radioligand Filter Binding Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0130	uM
3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)pyrrolo[3,4-d]pyrimidine-2,4-dione	503442: Displacement of [3H]5-[(3-hydroxypropyl)thio]-3-methyl-1-[2-(methyl-t)propyl-2,3-t2]-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione from MCT1 in human Jurkat cell membranes	ki	0.0155	uM
5-[(3R)-3-hydroxypyrrolidine-1-carbonyl]-3-methyl-6-[(2-methylbenzimidazol-1-yl)methyl]-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione	1798150: SPA Assay from Article 10.1016/j.bmcl.2006.01.024: “Potent blockers of the monocarboxylate transporter MCT1: novel immunomodulatory compounds.”	ki	0.0160	uM
6-[(4-azido-3-(125I)iodophenyl)methyl]-3-methyl-1-(2-methylpropyl)pyrrolo[3,4-d]pyridazin-4-one	503443: Displacement of [3H]5-[(3-hydroxypropyl)thio]-3-methyl-1-[2-(methyl-t)propyl-2,3-t2]-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione from human MCT1 expressed in INS1 cell membrane	ki	0.0230	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	5
AR C155858	affects binding, decreases activity, increases stability	5
Valproic Acid	affects expression, affects cotreatment, increases expression	5
Lactic Acid	increases stability, increases expression, increases reaction, decreases reaction, increases uptake (+4 more)	5
bisphenol A	decreases expression, decreases methylation, increases expression	4
trichostatin A	affects cotreatment, increases expression	4
Cadmium	increases response to substance, affects cotreatment, increases reaction, decreases reaction, increases abundance (+2 more)	4
Estradiol	affects cotreatment, decreases expression, increases expression, increases reaction	4
Tretinoin	decreases expression	3
Benzoic Acid	decreases reaction, increases uptake, increases expression, increases import	3
AZD3965	decreases reaction, increases expression, increases abundance, affects binding, decreases activity (+1 more)	2
methylmercuric chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Decitabine	affects methylation, affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Aspirin	affects reaction, increases uptake, decreases expression	2
Caffeine	affects reaction, increases uptake, increases expression, increases phosphorylation	2
Cisplatin	decreases reaction, increases expression, decreases response to substance	2
Indomethacin	decreases reaction, increases uptake, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases expression, affects cotreatment, increases reaction	2
Pyruvic Acid	decreases reaction, increases uptake	2
Genistein	affects cotreatment, affects expression, increases expression	2
p-Chloromercuribenzoic Acid	decreases reaction, increases uptake	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
4-oxoretinoic acid	decreases expression	1

ChEMBL screening assays

52 unique, capped per target: 49 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226685	Binding	Displacement of [3H]5-[(3-hydroxypropyl)thio]-3-methyl-1-[2-(methyl-t)propyl-2,3-t2]-6-(1-naphthalenylmethyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione from MCT1 in human Jurkat cell membranes	Monocarboxylate transporter MCT1 is a target for immunosuppression. — Nat Chem Biol
CHEMBL5723511	Functional	Affinity On-target Cellular interaction: (Inhibition of [14C]lactate uptake in SiHa cells) EUB0002482a SLC16A1	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Z0	Abcam A-549 SLC16A1 KO	Cancer cell line	Male
CVCL_D2D1	Abcam HCT 116 SLC16A1 KO	Cancer cell line	Male
CVCL_D2P5	Abcam THP-1 SLC16A1 KO	Cancer cell line	Male
CVCL_D4HX	HCT116-SLC16A1-KO-c6	Cancer cell line	Male
CVCL_D4HY	HCT116-SLC16A1-KO-c7	Cancer cell line	Male
CVCL_TL61	HAP1 SLC16A1 (-) 1	Cancer cell line	Male
CVCL_TL62	HAP1 SLC16A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04846751	Not specified	UNKNOWN	Exercise Type That Faster Reduces Postprandial Glycemia.