SLC22A2

Summary

SLC22A2 (solute carrier family 22 member 2, HGNC:10966) is a protein-coding gene on chromosome 6q25.3, encoding Solute carrier family 22 member 2 (O15244). Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption.

Source: NCBI Gene 6582 — RefSeq curated summary.

At a glance

• GWAS associations: 41
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 47 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10966
Approved symbol	SLC22A2
Name	solute carrier family 22 member 2
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Aliases	OCT2
Ensembl gene	ENSG00000112499
Ensembl biotype	protein_coding
OMIM	602608
Entrez	6582

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000366952, ENST00000366953, ENST00000486916, ENST00000489644, ENST00000491092, ENST00000498556

RefSeq mRNA: 1 — MANE Select: NM_003058 NM_003058

CCDS: CCDS5276

Canonical transcript exons

ENST00000366953 — 11 exons

Exon	Start	End
ENSE00000900967	160256614	160256717
ENSE00001443106	160216755	160217498
ENSE00001443107	160258344	160258821
ENSE00003462164	160245439	160245545
ENSE00003479468	160247184	160247298
ENSE00003496007	160224705	160224804
ENSE00003505971	160243572	160243786
ENSE00003580758	160249216	160249384
ENSE00003594582	160241474	160241586
ENSE00003615402	160250548	160250702
ENSE00003684689	160242294	160242402

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 92.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2058 / max 106.7358, expressed in 37 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76550	0.1001	29
76549	0.0905	16
76548	0.0086	4
76551	0.0067	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	92.77	gold quality
nephron tubule	UBERON:0001231	91.70	gold quality
renal medulla	UBERON:0000362	91.30	gold quality
metanephros cortex	UBERON:0010533	87.77	gold quality
kidney	UBERON:0002113	87.27	gold quality
kidney epithelium	UBERON:0004819	86.18	gold quality
cortex of kidney	UBERON:0001225	80.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.11	gold quality
renal glomerulus	UBERON:0000074	78.66	gold quality
metanephric glomerulus	UBERON:0004736	78.31	gold quality
metanephros	UBERON:0000081	75.39	gold quality
buccal mucosa cell	CL:0002336	74.74	gold quality
oocyte	CL:0000023	71.70	gold quality
secondary oocyte	CL:0000655	71.10	gold quality
cervix squamous epithelium	UBERON:0006922	68.21	gold quality
adult organism	UBERON:0007023	66.12	gold quality
right coronary artery	UBERON:0001625	61.37	gold quality
left coronary artery	UBERON:0001626	59.43	gold quality
coronary artery	UBERON:0001621	58.54	gold quality
diaphragm	UBERON:0001103	58.29	gold quality
tendon of biceps brachii	UBERON:0008188	57.50	gold quality
ascending aorta	UBERON:0001496	56.68	gold quality
thoracic aorta	UBERON:0001515	56.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.77	silver quality
aorta	UBERON:0000947	55.73	gold quality
popliteal artery	UBERON:0002250	55.28	gold quality
tibial artery	UBERON:0007610	55.27	gold quality
descending thoracic aorta	UBERON:0002345	55.08	gold quality
left ventricle myocardium	UBERON:0006566	54.70	gold quality
colonic epithelium	UBERON:0000397	54.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CASP3	Activation
CDK1	Activation

Upstream regulators (CollecTRI, top): AP1, AR, PAX5, POU2F2, USF1

miRNA regulators (miRDB)

33 targeting SLC22A2, 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-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-630	97.50	66.38	921
HSA-MIR-3674	97.01	68.86	1171

Literature-anchored findings (GeneRIF, showing 40)

• The human organic cation transporter (hOCT2) recognizes the degree of substrate ionization (PMID:11953440)
• cDNA coding hOCT2-A was isolated from human kidney. an alternatively spliced variant of hOCT2 with an insertion of 1169 bp. open reading frame encodes 483-amino acid protein with 81% amino acid identity with hOCT2. (PMID:12089365)
• polymorphisms in kidney exhibit altered function (PMID:12142729)
• inhibited by PI3K and PKA and activated by a CaM-dependent signaling pathway (PMID:12388397)
• OCT2 efficiently translocates agmatine and must be considered for the control of agmatine levels. (PMID:12538837)
• organic cation transporter EMT mRNA was mainly detected in the intra lobular septa and together with organic cation transporters OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias (PMID:15135235)
• OCT1 and OCT2 mediate luminal ACh release in human airways (PMID:15817714)
• Ranitidine and famotidine elicited differential inhibitory activities on SLC22A2. (PMID:16141367)
• uptake of cis-platin is mediated by hOCT2 in renal proximal tubules; cis-platin with other substrates that compete for hOCT2 offers an effective option to decrease nephrotoxicity in the clinical setting. (PMID:16314463)
• N-glycosylation of OCT2 has a profound effect on plasma membrane expression, substrate affinity, and maximum rate of substrate transport (PMID:16368738)
• OCT1 and OCT2 are major determinants of the anticancer activity of oxaliplatin and may contribute to its antitumor specificity. (PMID:16951202)
• data demonstrate that cysteine 474 of OCT2 is exposed to the aqueous milieu of the cleft and contributes to forming a pathway for organic cation transport (PMID:16990275)
• This study further suggests a function of OCT2 in blood pressure homeostasis and points to the potential role of the transporter in the development of essential hypertension. (PMID:17060063)
• findings suggest that genetic variants of hOCTs are not linked among three genes in a Korean population, and several of the hOCT genetic variants cause decreased transport activity in vitro compared with the wild type (PMID:17220237)
• PMAT, EMT, and OCT2 transporters are expressed in the endometrial stroma and can potentially regulate reuptake of monoamines in general and histamine in particular. (PMID:17393420)
• The results suggest that hOCT2 and hMATE1 mediate paraquat transport in the kidney. (PMID:17495125)
• Varenicline was characterized as a moderate-affinity substrate for hOCT2 (K(m)=370 microM) and its hOCT2-mediated uptake was partially inhibited by cimetidine. (PMID:17971819)
• Investigation of influences of regulatory single nucleotide polymorphisms (SNPs) of SLC22A in the kidney identifies a regulatory SNP that reduces human OCT2 promoter activity; one (insignificant) deletion polymorphism (-578_-576delAAG) is found. (PMID:18414781)
• These results indicate that kidney-specific expression of human OCT2 is regulated by methylation of the proximal promoter region, interfering with the transactivation by USF1. (PMID:18508876)
• The 808G>T polymorphism is associated with a reduced metformin renal or tubular clearance. (PMID:18551044)
• Known variants in SLC22A2 do not substantially contribute to explaining interindividual pharmacokinetic variability, suggesting that other mechanisms, controlling OCT2 expression, might be involved. (PMID:18559608)
• genetic variants (OCT2-T199I, -T201M, and -A270S) decreased the transport activity of metformin and thus may contribute to the inter-individual variation in metformin disposition (PMID:18728938)
• Genetic variation in OCT2 plays an important role in the renal clearance and net secretion of metformin in healthy volunteers. (PMID:19483665)
• we found that a nonsynonymous single-nucleotide polymorphism (SNP) in the OCT2 gene SLC22A2 (rs316019) was associated with reduced cisplatin-induced nephrotoxicity in patients (PMID:19625999)
• YM155 is a substrate for OCT1 and OCT2, whereas it is unlikely for OCT3. (PMID:19833842)
• This study showed that coordinate function of MATE1 with OCT2 likely contributes to the vectorial renal elimination of organic cationic drugs and that altered activity of MATE1 should be considered as a determinant of renal cationic drug elimination. (PMID:20053795)
• The hSLC22A2 drug transporter is a critical determinant in the uptake and cytotoxicity of various platinum compounds, particularly oxaliplatin. (PMID:20067471)
• The influence of organic cation transporters 1, 2, and 3 (OCT1, OCT2, and OCT3) and their genetic variants on cellular uptake of picoplatin and on the individual components of the ensuing cytotoxicity such as DNA adduct formation, was determined. (PMID:20371711)
• There was no clear association between the SLC22A1, SLC22A2, and SLC22A3 genes and diabetic nephropathy or hypertension (PMID:20429798)
• The results suggest that agmatine disposition may be influenced by hOCT2 and hMATE1, two transporters critical in the renal elimination of xenobiotic compounds. (PMID:21128598)
• Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics. (PMID:21346370)
• hOCT2 interacts with LAPTM4A in lysosomes and late endosomes and regulates endocytotic recruitment. (PMID:21553234)
• Data show that the cysteines of the large extracellular loop are important to enable correct folding, oligomeric assembly, and plasma membrane insertion of organic cation transporter 2 (hOCT2). (PMID:22085643)
• OCT2 plays a decisive role in the renal secretion of creatinine. This process can be inhibited by OCT2 substrates, which impair the usefulness of creatinine as a marker of renal function. (PMID:22223530)
• This mini-review discusses structural requirements for both OCT1 and OCT2 versus the blood-brain barrier choline transporter (BBBCHT) are discussed and compared. (PMID:22483271)
• results suggested that SLC22A2 gene polymorphism 808 G/T and cimetidine could attenuate cisplatin nephrotoxicity in Chinese cancer patients (PMID:22525860)
• The 808G>T single-nucleotide polymorphism in OCT2 ameliorated cisplatin-induced nephrotoxicity without alteration of disposition, whereas the rs2289669 G>A single-nucleotide polymorphism in MATE1 had no effect on cisplatin toxicity. (PMID:22569819)
• Conserved cysteines in the human organic cation transporter 2 (hOCT2), namely the six cysteines in the long extracellular loop (loop cysteines) and C474 in transmembrane helix 11, are important for plasma membrane targeting. (PMID:22573376)
• tryptophan can serve as one of the endogenous substrate for the OCT2 as well as a biomarker candidate indicating the variability of the transport activity of OCT2. (PMID:22590580)
• Seven polymorphisms in OCT1, OCT2, and MATE1 genes were compared between 53 type 2 diabetes patients with side effects of metformin and 193 metformin users without symptoms of metformin intolerance. (PMID:22735389)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a2	ENSDARG00000030530
mus_musculus	Slc22a2	ENSMUSG00000040966
rattus_norvegicus	Slc22a2	ENSRNOG00000016625
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	CG14691	FBGN0037829
drosophila_melanogaster	CG14855	FBGN0038260
drosophila_melanogaster	CG14856	FBGN0038261
drosophila_melanogaster	CG14857	FBGN0038262
drosophila_melanogaster	CG12783	FBGN0038448
drosophila_melanogaster	CG7333	FBGN0038715
drosophila_melanogaster	CG7342	FBGN0038716
drosophila_melanogaster	CG17751	FBGN0038717
drosophila_melanogaster	CG17752	FBGN0038718
drosophila_melanogaster	CG16727	FBGN0038719
drosophila_melanogaster	CG6231	FBGN0038720
drosophila_melanogaster	CG4465	FBGN0038750
drosophila_melanogaster	CG4462	FBGN0038752
drosophila_melanogaster	CG4459	FBGN0038753
drosophila_melanogaster	CG6356	FBGN0039178
drosophila_melanogaster	CG3690	FBGN0040350
drosophila_melanogaster	CG31103	FBGN0051103
drosophila_melanogaster	CG31106	FBGN0051106
drosophila_melanogaster	CG31272	FBGN0051272
drosophila_melanogaster	CG33233	FBGN0053233
drosophila_melanogaster	CG33234	FBGN0053234
drosophila_melanogaster	Orct2	FBGN0086365
drosophila_melanogaster	CG42269	FBGN0259164
drosophila_melanogaster	CG44098	FBGN0264907
caenorhabditis_elegans		WBGENE00003837
caenorhabditis_elegans	oct-1	WBGENE00003842
caenorhabditis_elegans		WBGENE00003843
caenorhabditis_elegans		WBGENE00006220
caenorhabditis_elegans		WBGENE00008110
caenorhabditis_elegans		WBGENE00011456
caenorhabditis_elegans		WBGENE00014127
caenorhabditis_elegans		WBGENE00017751
caenorhabditis_elegans		WBGENE00019408
caenorhabditis_elegans		WBGENE00020701
caenorhabditis_elegans		WBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A7 (ENSG00000137204), SLC22A23 (ENSG00000137266), SLC22A14 (ENSG00000144671), SLC22A3 (ENSG00000146477), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Solute carrier family 22 member 2 — O15244 (reviewed: O15244)

Alternative names: Organic cation transporter 2

All UniProt accessions (2): O15244, Q5T7Q5

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics. Functions as a Na(+)-independent, bidirectional uniporter. Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient. However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached. Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters. Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary ammonium compound choline. Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine. Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier. In contrast with isoform 1, not able to transport guanidine, creatinine, cimetidine and metformin.

Subcellular location. Basolateral cell membrane. Basal cell membrane. Apical cell membrane.

Tissue specificity. Mainly expressed in kidney, in the cortex and medulla. Localized in testis, mostly to peritubular myoid cells and Leydig cells and also detected along the basal membrane of Sertoli cells. Expressed in brain, in neurons of the cerebral cortex and in various subcortical nuclei. In the brain, also detected in the dopaminergic regions of the substantia nigra. Expressed in tracheal and bronchial ciliated epithelium in the respiratory tract. Also detected in secretory phase endometrium, in scattered stromal cells. Expressed in spleen, placenta, small intestine and spinal cord. Weakly expressed in prostate, uterus and lung. Mainly expressed in kidney, bone marrow and testis. Expressed in colon, skeletal muscle, spinal cord, placenta and liver.

Post-translational modifications. Tyrosine phosphorylated by tyrosine-protein kinase YES1.

Activity regulation. Tyrosine phosphorylation of the transporter leads to activation of the transport activity. TEA uptake is activated by tyrosine phosphorylation. Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2.

Domain organisation. Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is required for the activation of substrate transport.

Induction. May be down-regulated in diabetic patients.

Miscellaneous. Mediates the renal secretion of many clinically used cationic drugs. Transports drugs such as diabetes treatment medicine metformin, 1-methyl-4-phenylpyridinium (MPP(+)), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, platinum-based drugs cisplatin and oxaliplatin, 3’-azido-3’-deoxythymidine (AZT) and tetraethylammonium (TEA). Mediates the bidirectional transport of MPP(+). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity. Involved in cisplatin-induced nephrotoxicity.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15244-1	1	yes
O15244-2	2, OCT2-A
O15244-3	3

RefSeq proteins (1): NP_003049* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004749	Orgcat_transp/SVOP	Family
IPR005828	MFS_sugar_transport-like	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 12 shown:

• choline(out) = choline(in) (RHEA:32751)
• thiamine(in) = thiamine(out) (RHEA:34919)
• spermidine(in) = spermidine(out) (RHEA:35039)
• prostaglandin E2(out) = prostaglandin E2(in) (RHEA:50984)
• prostaglandin F2alpha(out) = prostaglandin F2alpha(in) (RHEA:50988)
• agmatine(out) = agmatine(in) (RHEA:72131)
• putrescine(out) = putrescine(in) (RHEA:72135)
• 1-methylnicotinamide(out) = 1-methylnicotinamide(in) (RHEA:73859)
• dopamine(out) = dopamine(in) (RHEA:73863)
• serotonin(out) = serotonin(in) (RHEA:73867)
• (R)-noradrenaline(out) = (R)-noradrenaline(in) (RHEA:73871)
• (R)-adrenaline(out) = (R)-adrenaline(in) (RHEA:73875)

UniProt features (56 total): mutagenesis site 15, topological domain 13, transmembrane region 12, sequence variant 8, splice variant 4, chain 1, short sequence motif 1, site 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8ET9	ELECTRON MICROSCOPY	3.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15244-F1	83.02	0.32

Functional residue map

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

Catalytic / active sites (1): 451 (involved in recognition of organic cations and participates in structural changes that occur during translocation of organic cations)

Glycosylation sites (1): 72

Mutagenesis-validated functional residues (15):

Position	Phenotype
73	no change in tea uptake.
92	no change in tea uptake.
128	no change in tea uptake.
169	no change in tea uptake.
241	slight decrease in tea uptake. no change in tyrosine phosphorylation. strong decrease in tea uptake; when associated wit
257	no change in tea uptake.
279	no change in tea uptake.
280	no change in tea uptake.
284	decreased tea and metformin uptake. decreased tyrosine phosphorylation.
286	no change in tea and metformin uptake. no change in tyrosine phosphorylation.
287	decreased tea and metformin uptake. decreased tyrosine phosphorylation.
362	decreased tea uptake and yes1-mediated tyrosine phosphorylation. strong decrease in tea uptake; when associated with f-2
377	slight decrease in tea uptake. no change in tyrosine phosphorylation. strong decrease in tea uptake; when associated wit
458	no change in tea uptake.
544	no change in tea uptake.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-112311	Neurotransmitter clearance
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-2161517	Abacavir transmembrane transport
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-2161522	Abacavir ADME
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-549132
R-HSA-9748784	Drug ADME

MSigDB gene sets: 207 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, GTCTACC_MIR379, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, chr6q25, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, MARTINEZ_RB1_TARGETS_DN, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT, REACTOME_NOREPINEPHRINE_NEUROTRANSMITTER_RELEASE_CYCLE, WTGAAAT_UNKNOWN, TGTGTGA_MIR377

GO Biological Process (34): monoatomic cation transport (GO:0006812), neurotransmitter transport (GO:0006836), obsolete serotonin transport (GO:0006837), body fluid secretion (GO:0007589), obsolete organic cation transport (GO:0015695), prostaglandin transport (GO:0015732), amine transport (GO:0015837), putrescine transport (GO:0015847), spermidine transport (GO:0015848), acetylcholine transport (GO:0015870), choline transport (GO:0015871), obsolete dopamine transport (GO:0015872), obsolete norepinephrine transport (GO:0015874), xenobiotic transport (GO:0042908), obsolete epinephrine transport (GO:0048241), histamine transport (GO:0051608), serotonin uptake (GO:0051610), histamine uptake (GO:0051615), norepinephrine uptake (GO:0051620), thiamine transmembrane transport (GO:0071934), purine-containing compound transmembrane transport (GO:0072530), amino acid import across plasma membrane (GO:0089718), dopamine uptake (GO:0090494), L-arginine import across plasma membrane (GO:0097638), export across plasma membrane (GO:0140115), transport across blood-brain barrier (GO:0150104), L-alpha-amino acid transmembrane transport (GO:1902475), cellular detoxification (GO:1990748), xenobiotic transport across blood-brain barrier (GO:1990962), monoatomic ion transport (GO:0006811), quaternary ammonium group transport (GO:0015697), transmembrane transport (GO:0055085), spermidine transmembrane transport (GO:1903711), L-arginine transmembrane transport (GO:1903826)

GO Molecular Function (19): amine transmembrane transporter activity (GO:0005275), acetylcholine transmembrane transporter activity (GO:0005277), neurotransmitter transmembrane transporter activity (GO:0005326), monoamine transmembrane transporter activity (GO:0008504), obsolete organic anion transmembrane transporter activity (GO:0008514), obsolete organic cation transmembrane transporter activity (GO:0015101), prostaglandin transmembrane transporter activity (GO:0015132), L-amino acid transmembrane transporter activity (GO:0015179), pyrimidine nucleoside transmembrane transporter activity (GO:0015214), choline transmembrane transporter activity (GO:0015220), thiamine transmembrane transporter activity (GO:0015234), putrescine transmembrane transporter activity (GO:0015489), efflux transmembrane transporter activity (GO:0015562), spermidine transmembrane transporter activity (GO:0015606), quaternary ammonium group transmembrane transporter activity (GO:0015651), toxin transmembrane transporter activity (GO:0019534), xenobiotic transmembrane transporter activity (GO:0042910), L-arginine transmembrane transporter activity (GO:0061459), transmembrane transporter activity (GO:0022857)

GO Cellular Component (7): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transmission across Chemical Synapses	2
SLC-mediated transmembrane transport	2
Neurotransmitter release cycle	1
Abacavir ADME	1
Neuronal System	1
Drug ADME	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transporter activity	7
nitrogen compound transport	5
plasma membrane region	3
transport	2
polyamine transport	2
pyrimidine-containing compound transmembrane transport	2
polyamine transmembrane transporter activity	2
cellular anatomical structure	2
monoatomic ion transport	1
secretion	1
regulation of body fluid levels	1
fatty acid transport	1
icosanoid transport	1
acetate ester transport	1
organic hydroxy compound transport	1
neurotransmitter reuptake	1
neurotransmitter uptake	1
histamine transport	1
catecholamine uptake	1
thiamine transport	1
vitamin transmembrane transport	1
azole transmembrane transport	1
amine transport	1
neurotransmitter transmembrane transporter activity	1
acetate ester transmembrane transporter activity	1
neurotransmitter transport	1
active transmembrane transporter activity	1
prostaglandin transport	1
icosanoid transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
carboxylic acid transmembrane transporter activity	1
L-alpha-amino acid transmembrane transport	1
nucleoside transmembrane transporter activity	1
choline transport	1
thiamine transmembrane transport	1
vitamin transmembrane transporter activity	1
azole transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
putrescine transport	1
spermidine transmembrane transport	1

Protein interactions and networks

STRING

1462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A2	SLC47A1	Q96FL8	888
SLC22A2	IGF2R	P11717	884
SLC22A2	SLC47A2	Q86VL8	881
SLC22A2	EHMT2	Q96KQ7	733
SLC22A2	SLC31A1	O15431	706
SLC22A2	SLC6A2	P23975	690
SLC22A2	YRDC	Q86U90	686
SLC22A2	SLCO1B1	Q9Y6L6	672
SLC22A2	SLCO1B3	Q9NPD5	671
SLC22A2	Q92681	Q92681	658
SLC22A2	SLC29A4	Q7RTT9	632
SLC22A2	SLC15A2	Q16348	622
SLC22A2	ABCG2	Q9UNQ0	608
SLC22A2	ABCC2	Q92887	595
SLC22A2	ABCB1	P08183	593

IntAct

11 interactions, top by confidence:

A	B	Type	Score
EXT2	SLC22A2	psi-mi:“MI:0915”(physical association)	0.550
SLC22A2	ETV5	psi-mi:“MI:0915”(physical association)	0.370
GTF2B	SLC22A2	psi-mi:“MI:0915”(physical association)	0.370
SUMO2	SLC22A2	psi-mi:“MI:0915”(physical association)	0.370
HYAL3	SLC22A2	psi-mi:“MI:0915”(physical association)	0.370
SLC22A2	LSM4	psi-mi:“MI:0915”(physical association)	0.370
SLC22A2	CST9L	psi-mi:“MI:0915”(physical association)	0.370
SLC22A2	AGO3	psi-mi:“MI:0915”(physical association)	0.370
SLC22A2	FADS1	psi-mi:“MI:0914”(association)	0.350
SLC22A2	RAB27B	psi-mi:“MI:0914”(association)	0.350

BioGRID (110): SLC22A2 (Synthetic Lethality), CCL2 (PCA), CD63 (PCA), CD9 (PCA), CYB5R3 (PCA), FIS1 (PCA), HNRNPH3 (PCA), LAPTM4A (PCA), LAPTM4B (PCA), PDIA6 (PCA), PDZK1IP1 (PCA), SERP1 (PCA), SPCS1 (PCA), TMEM134 (PCA), TMEM176B (PCA)

ESM2 similar proteins: A6NK97, A6QLW8, A7MBE0, A9CB25, B2GV36, O02713, O08966, O15244, O15245, O35956, O57379, O70577, O70594, O75751, O76082, O77504, O88446, O88909, Q1RPP5, Q3YAW7, Q4W8A2, Q5R540, Q5R5H7, Q5R9C4, Q5RLM2, Q63089, Q66J54, Q6A4L0, Q6DFR1, Q6NUB3, Q6NYN7, Q70BM6, Q80UJ1, Q863T6, Q86VW1, Q8HY24, Q8MJI6, Q8TCC7, Q8VC69, Q91WU2

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, B2GV36, G1SZD9, O15244, O35956, O57379, O70577, O70594, O75751, O77504, O88446, O88909, P55705, Q1RPP5, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5EXK5, Q5R540, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63ZE4, Q66J52, Q66J54, Q6A4L0, Q6NYN7, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q864Z3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1766 predictions. Top by Δscore:

Variant	Effect	Δscore
6:160224700:CCTA:C	donor_loss	1.0000
6:160224701:CTAC:C	donor_loss	1.0000
6:160224702:TACC:T	donor_loss	1.0000
6:160224703:A:AG	donor_loss	1.0000
6:160224704:C:CG	donor_loss	1.0000
6:160224801:ACGCC:A	acceptor_loss	1.0000
6:160224802:CGC:C	acceptor_gain	1.0000
6:160224802:CGCCT:C	acceptor_loss	1.0000
6:160224803:GCCT:G	acceptor_loss	1.0000
6:160224805:CTGAA:C	acceptor_loss	1.0000
6:160224806:T:A	acceptor_loss	1.0000
6:160241468:TCTTA:T	donor_loss	1.0000
6:160241469:CTTA:C	donor_loss	1.0000
6:160241470:TTA:T	donor_loss	1.0000
6:160241471:TACC:T	donor_loss	1.0000
6:160241472:A:AC	donor_gain	1.0000
6:160241472:A:AG	donor_loss	1.0000
6:160241473:C:CC	donor_gain	1.0000
6:160241473:C:CT	donor_loss	1.0000
6:160241584:TTC:T	acceptor_gain	1.0000
6:160241584:TTCCT:T	acceptor_loss	1.0000
6:160241585:TCC:T	acceptor_loss	1.0000
6:160241586:CCT:C	acceptor_loss	1.0000
6:160241587:C:CC	acceptor_gain	1.0000
6:160241588:T:G	acceptor_loss	1.0000
6:160245437:A:AC	donor_gain	1.0000
6:160245438:C:CC	donor_gain	1.0000
6:160245544:CG:C	acceptor_gain	1.0000
6:160245546:C:CC	acceptor_gain	1.0000
6:160247169:AAGGC:A	donor_gain	1.0000

AlphaMissense

3618 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:160258563:C:A	W65C	0.995
6:160258563:C:G	W65C	0.995
6:160249272:C:A	W262C	0.994
6:160249272:C:G	W262C	0.994
6:160258380:C:A	W126C	0.993
6:160258380:C:G	W126C	0.993
6:160258606:C:G	C51S	0.992
6:160258607:A:T	C51S	0.992
6:160258632:G:C	F42L	0.992
6:160258632:G:T	F42L	0.992
6:160258634:A:G	F42L	0.992
6:160242294:C:A	R463M	0.991
6:160256715:A:C	F139L	0.990
6:160256715:A:T	F139L	0.990
6:160256717:A:G	F139L	0.990
6:160258470:C:A	W96C	0.990
6:160258470:C:G	W96C	0.990
6:160241565:A:C	C470W	0.989
6:160241578:C:T	G466D	0.989
6:160256704:C:G	C143S	0.989
6:160256705:A:T	C143S	0.989
6:160242320:A:C	N454K	0.988
6:160242320:A:T	N454K	0.988
6:160242312:A:G	L457P	0.987
6:160247272:A:G	L290P	0.987
6:160250590:C:G	G211R	0.987
6:160250590:C:T	G211R	0.987
6:160241579:C:G	G466R	0.986
6:160243777:G:C	S358R	0.986
6:160243777:G:T	S358R	0.986

dbSNP variants (sampled 300 via entrez): RS1000063370 (6:160256007 T>C), RS1000271424 (6:160222397 C>T), RS1000329175 (6:160238858 A>G), RS1000496628 (6:160223921 G>A,T), RS1000531499 (6:160233463 C>A,T), RS1000554457 (6:160232945 T>G), RS1000641815 (6:160229438 T>C,G), RS1000696100 (6:160218040 A>G), RS1000883192 (6:160220922 A>G), RS1001029492 (6:160226401 G>A), RS1001205922 (6:160257044 G>T), RS1001223721 (6:160243646 C>A,G,T), RS1001239639 (6:160227525 C>A), RS1001249756 (6:160227275 A>G), RS1001256503 (6:160233736 C>T)

Disease associations

OMIM: gene MIM:602608 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000649_9	Chronic kidney disease	6.000000e-12
GCST000651_5	Creatinine levels	7.000000e-10
GCST002783_178	Body mass index	5.000000e-07
GCST002783_282	Body mass index	2.000000e-06
GCST002944_56	Prostate cancer	1.000000e-19
GCST003127_13	Lipoprotein (a) levels	2.000000e-34
GCST003335_3	Waist circumference	3.000000e-08
GCST003335_8	Waist circumference	2.000000e-07
GCST003372_18	Glomerular filtration rate (creatinine)	4.000000e-19
GCST003401_15	Glomerular filtration rate in non diabetics (creatinine)	5.000000e-11
GCST003790_21	Glomerular filtration rate	1.000000e-09
GCST004292_18	Glomerular filtration rate (creatinine)	1.000000e-15
GCST005950_13	Body mass index x sex x age interaction (4df test)	3.000000e-07
GCST005951_54	Body mass index	4.000000e-06
GCST005952_6	Body mass index (age>50)	2.000000e-08
GCST005984_31	Glomerular filtration rate	7.000000e-12
GCST005985_49	Creatinine levels	1.000000e-11
GCST006088_12	Familial squamous cell lung carcinoma	2.000000e-06
GCST006249_79	Serum metabolite levels	2.000000e-72
GCST007344_104	Estimated glomerular filtration rate	2.000000e-09
GCST007344_77	Estimated glomerular filtration rate	6.000000e-07
GCST007344_8	Estimated glomerular filtration rate	3.000000e-25
GCST007344_88	Estimated glomerular filtration rate	4.000000e-22
GCST007876_126	Estimated glomerular filtration rate	6.000000e-32
GCST007877_9	Creatinine levels	1.000000e-14
GCST008058_196	Estimated glomerular filtration rate	3.000000e-92
GCST008059_108	Estimated glomerular filtration rate	1.000000e-82
GCST008064_45	Chronic kidney disease	1.000000e-10
GCST008433_4	Lipoprotein (a) levels in coronary artery disease (percutaneous coronary intervention)	7.000000e-08
GCST008745_61	Estimated glomerular filtration rate in non-diabetics	2.000000e-27

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006925	lipoprotein A measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006953	family history of lung cancer
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1743122 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

47 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 637,952 (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
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1106	EPINASTINE	4	8,530
CHEMBL1200629	VECURONIUM BROMIDE	4	5,399
CHEMBL1229211	DOLUTEGRAVIR	4	3,337
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1502	PANTOPRAZOLE	4	14,689
CHEMBL163	RITONAVIR	4	53,773
CHEMBL170	QUININE	4	108,216
CHEMBL170988	PHENFORMIN	4	37,492
CHEMBL1732	DIHYDROERGOTAMINE	4	12,897
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL219916	DOMPERIDONE	4	18,305
CHEMBL289469	GRANISETRON	4	431
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL30	CIMETIDINE	4	47,191
CHEMBL339427	TUBOCURARINE	4	4,123
CHEMBL364713	NOSCAPINE	4	14,987
CHEMBL3989866	BICTEGRAVIR	4	1,306
CHEMBL46	ONDANSETRON	4	41,386
CHEMBL481	IRINOTECAN	4
CHEMBL49	BUSPIRONE	4
CHEMBL517	DISOPYRAMIDE	4
CHEMBL55	PENTAMIDINE	4
CHEMBL58	MITOXANTRONE	4
CHEMBL603	ZAFIRLUKAST	4
CHEMBL640	PROCAINAMIDE	4
CHEMBL660	AMANTADINE	4
CHEMBL691	ETHINYL ESTRADIOL	4
CHEMBL72	DESIPRAMINE	4

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs316019	Other	3	l-tryptophan
rs316019	Other	3	metformin
rs316019	Toxicity	3	cisplatin	Neoplasms
rs316019	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma
rs316019	Toxicity	3	cisplatin	Ototoxicity
rs316019	Toxicity	4	anthracyclines and related substances	Neoplasms

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs316019	SLC22A2	3	5.00	6	anthracyclines and related substances;metformin;l-tryptophan;cisplatin;Platinum compounds
rs8177516	SLC22A2		0.00	0
rs145450955	SLC22A2		0.00	0
rs316003	SLC22A2		0.00	0
rs316009	SLC22A2		0.00	0
rs315978	SLC22A2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Organic cation transporters (OCT)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
decynium 22	Inhibition	7.0	pKi

Binding affinities (BindingDB)

33 measured of 33 human assays (33 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R,5S,13aR)-N-(2-chloro-4-fluorobenzyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][3]oxazepine-10-carboxamide	IC50	42 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2R,5S,13aR)—N-(2-chloro-4-fluorobenzyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	42 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-(2,4,5-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	94 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(13aS)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	137 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(13aS)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	137 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(2R,3S,5R,3aS)-N-(2,4-difluorobenzyl)-8-hydroxy-3-methyl-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	204 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,11R,13S)-N-[(2,4-difluorophenyl)methyl]-5-hydroxy-14-methyl-3,6-dioxo-12-oxa-2,9-diazatetracyclo[11.2.1.02,11.04,9]hexadeca-4,7-diene-7-carboxamide	IC50	204 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(2R,5S,13aR)-N-(2,4-difluorobenzyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	240 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2S,5R,13aS)-N-(2,4-difluorobenzyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	250 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1R,11R,13S)-N-[(2,4-difluorophenyl)methyl]-5-hydroxy-3,6-dioxo-12-oxa-2,9-diazatetracyclo[11.2.1.02,11.04,9]hexadeca-4,7-diene-7-carboxamide	IC50	250 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,11S,13R)-N-[(2,4-difluorophenyl)methyl]-5-hydroxy-14-methyl-3,6-dioxo-12-oxa-2,9-diazatetracyclo[11.2.1.02,11.04,9]hexadeca-4,7-diene-7-carboxamide	IC50	358 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-ethanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	450 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1R,4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-ethanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	450 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,4S,12aS)-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	476 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2, 1-b][1,3]oxazepine-10-carboxamide	IC50	487 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	487 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(2S,5R,13aS)-N—((S)-1-(2,4-difluorophenyl)ethyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	610 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1R,3R,11aS)-6-hydroxy-5,7-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,5,7,11,11a-hexahydro-1H-1,3-methanopyrido[1,2-a]pyrrolo[1,2-d]pyrazine-8-carboxamide	IC50	1360 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1R,3R,11aS)-6-hydroxy-5,7-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,5,7,11,11a-hexahydro-1H-1,3-methanopyrido[1,2-a]pyrrolo[1,2-d]pyrazine-8-carboxamide	IC50	1360 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,3S,4R,12aR)-7-hydroxy-3-methyl-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	1510 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(4R,12aS)-N-(1-(2,4-difluorophenyl)cyclopropyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxamide	IC50	2230 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(3S,7R)-N-[1-(2,4-difluorophenyl)cyclopropyl]-11-methoxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-13-carboxamide	IC50	2230 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,4S,12aR)-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	2820 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,4R,12aR)-3,3-difluoro-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	3730 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1R,4S,12aR)-7-hydroxy-6,8-dioxo-N—((R)-1-(2,4,6-trifluorophenyl)ethyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	3830 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	4910 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,4R,12aS)—N-(2,4-difluorobenzyl)-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	4910 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections
(1R,4S,12aR)-N-(2,4-difluorobenzyl)-7-hydroxy-6,8-dioxo-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	6200 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2S,5R,13aS)-N—((R)-1-(2,4-difluorophenyl)ethyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide	IC50	10000 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(2S,5R)-N—((S)-1-(2,4-difluorophenyl)-2,2,2-trifluoroethyl)-8-hydroxy-7,9-dioxo-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1′,2′:4,5]pyrazino[2, 1-b][1,3]oxazepine-10-carboxamide	IC50	10000 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,3R,4R,12aR)-3-fluoro-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	10000 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,4R,12aS)-3,3-difluoro-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	10000 nM	US-9663528: Substituted 1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1’,2’-d]pyrazines and methods for treating viral infections
(1S,3R,4R,12aR)-3-fluoro-7-hydroxy-6,8-dioxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4,6,8,12,12a-octahydro-1,4-methanodipyrido[1,2-a:1′,2′-d]pyrazine-9-carboxamide	IC50	10000 nM	US-9732092: Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections

ChEMBL bioactivities

106 potent at pChembl≥5 of 150 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.38	IC50	42	nM	CHEMBL5864617
7.38	IC50	42	nM	CHEMBL5995971
7.03	IC50	94	nM	CHEMBL5870848
7.00	IC50	100	nM	CHEMBL2074900
7.00	Ki	100	nM	CHEMBL1197556
6.86	IC50	137	nM	CHEMBL6000266
6.86	IC50	137	nM	CHEMBL6056512
6.86	IC50	137	nM	CHEMBL5962549
6.69	IC50	204	nM	CHEMBL6049097
6.69	IC50	204	nM	CHEMBL5830493
6.68	Ki	210	nM	Cyanine-863
6.62	IC50	240	nM	CHEMBL5819083
6.60	IC50	250	nM	CHEMBL6066002
6.60	IC50	250	nM	CHEMBL5761245
6.45	IC50	358	nM	CHEMBL6049097
6.45	IC50	358	nM	CHEMBL5841931
6.40	IC50	400	nM	CHLORHEXIDINE
6.35	IC50	450	nM	CHEMBL5843001
6.35	IC50	450	nM	CHEMBL6047421
6.35	IC50	450	nM	CHEMBL5823398
6.32	IC50	476	nM	CHEMBL5792941
6.31	IC50	487	nM	BICTEGRAVIR
6.31	IC50	487	nM	CHEMBL6028654
6.22	IC50	600	nM	IMIPRAMINE
6.21	IC50	610	nM	CHEMBL5882513
6.17	IC50	680	nM	TACRINE
6.05	IC50	890	nM	ONDANSETRON
6.05	IC50	900	nM	GABEXATE
5.95	IC50	1130	nM	CHEMBL1197556
5.92	IC50	1200	nM	PENTAMIDINE
5.87	IC50	1357	nM	CHEMBL5792941
5.87	IC50	1357	nM	CHEMBL6013817
5.87	IC50	1357	nM	CHEMBL5977043
5.82	Ki	1500	nM	TETRAPENTYLAMMONIUM
5.82	IC50	1500	nM	PANTOPRAZOLE
5.82	IC50	1506	nM	CHEMBL5916318
5.77	IC50	1700	nM	ONDANSETRON
5.72	IC50	1900	nM	BITHIONOL
5.72	IC50	1900	nM	DOLUTEGRAVIR
5.66	IC50	2200	nM	ETHINYL ESTRADIOL
5.65	IC50	2230	nM	CHEMBL5827479
5.65	IC50	2230	nM	CHEMBL5769471
5.62	Ki	2400	nM	CHEMBL311617
5.60	IC50	2500	nM	ORPHENADRINE
5.58	IC50	2600	nM	DIPYRIDAMOLE
5.58	IC50	2600	nM	NOSCAPINE
5.57	IC50	2700	nM	IRINOTECAN
5.55	IC50	2823	nM	CHEMBL5932213
5.54	IC50	2900	nM	DISOPYRAMIDE
5.47	Ki	3400	nM	QUININE

PubChem BioAssay actives

37 with measured affinity, of 259 total; 35 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
N-(2-chloroethyl)-N-methyl-9H-fluoren-9-amine	681561: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT2-expressing HEK293 cells	ic50	0.1000	uM
(2E)-1-ethyl-2-[(1-ethylquinolin-1-ium-2-yl)methylidene]quinoline	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	0.1000	uM
2-[(3,6-dimethyl-2-phenyl-4H-pyrimidin-4-yl)methyl]-1-ethylquinolin-1-ium chloride	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	0.2100	uM
Chlorhexidine	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	0.4000	uM
Imipramine	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	0.6000	uM
1,2,3,4-tetrahydroacridin-9-amine	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	0.6800	uM
Ondansetron	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	0.8900	uM
ethyl 4-[6-(diaminomethylideneamino)hexanoyloxy]benzoate	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	0.9000	uM
Pentamidine	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	1.2000	uM
tetrapentylazanium	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	1.5000	uM
Pantoprazole	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	1.5000	uM
2,4-dichloro-6-(3,5-dichloro-2-hydroxyphenyl)sulfanylphenol	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	1.9000	uM
Dolutegravir	1211974: Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis	ic50	1.9000	uM
ethinyl estradiol	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	2.2000	uM
1-methyl-4-phenylpyridin-1-ium	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	2.4000	uM
Orphenadrine	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	2.5000	uM
(3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3H-2-benzofuran-1-one	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	2.6000	uM
Dipyridamole	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	2.6000	uM
Irinotecan	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	2.7000	uM
Disopyramide	692192: Inhibition of human OCT2 expressed in HEK-293-Flp-In cells incubated for 3 mins by ASP+ substrate uptake assay	ic50	2.9000	uM
Quinine	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	3.4000	uM
Vecuronium Bromide	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	3.5000	uM
Imatinib	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	4.2000	uM
Epinastine	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	4.3000	uM
1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	4.3000	uM
2-(4-iodophenyl)guanidine	1463535: Inhibition of human OCT2 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	4.4000	uM
Rimantadine	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	4.4000	uM
Dabigatran	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	4.7000	uM
5-methyl-1-(1-methylpiperidin-1-ium-1-yl)-4-phenylhexan-3-ol bromide	681171: TP_TRANSPORTER: inhibition of TEA uptake in Xenopus laevis oocytes	ki	4.8000	uM
Phenoxybenzamine	681561: TP_TRANSPORTER: inhibition of MPP+ uptake (MPP+: 0.25 uM) in OCT2-expressing HEK293 cells	ic50	4.9000	uM
Carvedilol	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	7.5000	uM
Domperidone	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	7.9000	uM
2-(4-tert-butylphenyl)guanidine	1463535: Inhibition of human OCT2 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	8.3000	uM
2-(4-methylphenyl)guanidine	1463535: Inhibition of human OCT2 expressed in HEK293 cells assessed as decrease in uptake of substrate [3H]MPP+ after 1 min by liquid scintillation counting method	ic50	9.3000	uM
Zafirlukast	721751: Inhibition of human OCT2-mediated ASP+ uptake expressed in HEK293 cells after 3 mins by fluorescence assay	ic50	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetraethylammonium	increases uptake, increases reaction, affects transport, decreases activity, decreases uptake (+2 more)	13
1-Methyl-4-phenylpyridinium	decreases reaction, increases uptake, increases transport, decreases uptake, increases import	11
Amitriptyline	decreases activity, decreases reaction, increases import, increases uptake	5
Cimetidine	decreases reaction, increases uptake, affects transport, decreases response to substance	5
Metformin	decreases reaction, increases uptake, affects transport, decreases transport	5
Quinine	increases uptake, decreases activity, decreases reaction, increases transport	5
Famotidine	affects transport, decreases reaction, increases uptake	4
Atropine	increases transport, increases uptake, decreases reaction	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation, increases mutagenesis	3
Phenoxybenzamine	affects transport, decreases reaction, increases uptake, decreases activity	3
Ranitidine	decreases reaction, increases transport, increases uptake	3
4-(4-dimethylaminostyryl)-1-methylpyridinium	decreases reaction, increases uptake	2
Oxaliplatin	decreases reaction, increases uptake, increases import, increases response to substance	2
Resveratrol	affects cotreatment, decreases expression	2
Carvedilol	decreases reaction, increases uptake	2
Clonidine	increases uptake, decreases reaction, increases transport	2
Diphenhydramine	decreases reaction, increases transport, increases uptake	2
Nicotine	decreases reaction, increases uptake, affects response to substance	2
Quinidine	increases uptake, decreases reaction	2
Tobacco Smoke Pollution	decreases reaction, increases import, decreases activity, increases expression	2
Ondansetron	increases uptake, decreases reaction	2
GSK-J4	increases expression	1
bisphenol F	increases reaction, increases uptake	1
AB-FUBINACA	decreases activity	1
parthenolide	decreases reaction, increases uptake	1
nimetazepam	decreases reaction, increases uptake	1
trospium chloride	decreases activity	1
3,3’,4’,5-tetrachlorosalicylanilide	decreases reaction, increases uptake	1
clorprenaline	decreases reaction, increases uptake	1
clomacran	decreases reaction, increases uptake	1

ChEMBL screening assays

101 unique, capped per target: 62 functional, 21 admet, 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743149	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, OCT2	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL1771933	Binding	Inhibition of human OCT2	Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. — J Med Chem
CHEMBL2075992	Functional	TP_TRANSPORTER: uptake in Xenopus laevis oocytes	Carriers involved in targeting the cytostatic bile acid-cisplatin derivatives cis-diammine-chloro-cholylglycinate-platinum(II) and cis-diammine-bisursodeoxycholate-platinum(II) toward liver cells. — Mol Pharmacol

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5ZR	SA7K OCT2 KO	Transformed cell line	Female
CVCL_RM66	RPTEC/TERT1 OCT2	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

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