Target Information

Target General Information

Target ID

T70680 (Former ID: TTDS00504)

Target Name

Solute carrier family 22 member 8 (SLC22A8)

Synonyms

hROAT1; hPAHT; hOAT1; Solute carrier family 22 member 6; SLC22A8; SLC22A6; Renal organic anion transporter 1; PAHT; PAH transporter; OAT1

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Gene Name

SLC22A8

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Gout [ICD-11: FA25]

Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55]

Ocular disease [ICD-11: N.A.]

Function

Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc).

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BioChemical Class

Major facilitator superfamily

UniProt ID

S22A8_HUMAN

Sequence

MTFSEILDRVGSMGHFQFLHVAILGLPILNMANHNLLQIFTAATPVHHCRPPHNASTGPW
VLPMGPNGKPERCLRFVHPPNASLPNDTQRAMEPCLDGWVYNSTKDSIVTEWDLVCNSNK
LKEMAQSIFMAGILIGGLVLGDLSDRFGRRPILTCSYLLLAASGSGAAFSPTFPIYMVFR
FLCGFGISGITLSTVILNVEWVPTRMRAIMSTALGYCYTFGQFILPGLAYAIPQWRWLQL
TVSIPFFVFFLSSWWTPESIRWLVLSGKSSKALKILRRVAVFNGKKEEGERLSLEELKLN
LQKEISLAKAKYTASDLFRIPMLRRMTFCLSLAWFATGFAYYSLAMGVEEFGVNLYILQI
IFGGVDVPAKFITILSLSYLGRHTTQAAALLLAGGAILALTFVPLDLQTVRTVLAVFGKG
CLSSSFSCLFLYTSELYPTVIRQTGMGVSNLWTRVGSMVSPLVKITGEVQPFIPNIIYGI
TALLGGSAALFLPETLNQPLPETIEDLENWSLRAKKPKQEPEVEKASQRIPLQPHGPGLG
SS

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3D Structure

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AlphaFold

HIT2.0 ID

T50PQ4

Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

FLUORESCEIN

Drug Info

Approved

Ocular disease

[2]

Probenecid

Drug Info

Approved

Hyperuricaemia

[2], [3], [4]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

Buproprion+zonisamide

Drug Info

Phase 2

Obesity

[5]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 6 Inhibitor drugs

FLUORESCEIN

Drug Info

[6]

3R14S-OCHRATOXIN A

Drug Info

[6]

ADIPATE

Drug Info

[6]

AMINOHIPPURIC ACID

Drug Info

[6]

GLUTARATE

Drug Info

[6]

HEPTANOATE

Drug Info

[6]

Blocker

[+] 2 Blocker drugs

Probenecid

Drug Info

[1], [7]

Buproprion+zonisamide

Drug Info

[8]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Pathway Affiliation

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Organic anion transporter 7 (SLC22A9)	PF07690	38.182 (210/550)	3.07E-120
Solute carrier family 22 member 25 (SLC22A25)	PF07690	35.897 (196/546)	2.80E-112
Solute carrier family 22 member 7 (SLC22A7)	PF07690	37.615 (205/545)	6.45E-108
Organic cation transporter 3 (OCT3)	PF07690	32.496 (181/557)	1.97E-83

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Bile secretion	hsa04976	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Affiliated Biological Pathways

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Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Kidney Function

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 3

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4357).

REF 4

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 007898.

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024638)

REF 6

Structural variation governs substrate specificity for organic anion transporter (OAT) homologs. Potential remote sensing by OAT family members. J Biol Chem. 2007 Aug 17;282(33):23841-53.

REF 7

Interactions of organic anions with the organic cation transporter in renal BBMV. Am J Physiol. 1988 Jan;254(1 Pt 2):F56-61.

REF 8

Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.

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