Target Information

Target General Information

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Target ID

T06569 (Former ID: TTDR00210)

Target Name

Carbonic anhydrase VI (CA-VI)

Synonyms

Secreted carbonic anhydrase; Salivary carbonic anhydrase; Carbonic anhydrase 6; Carbonate dehydratase VI

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Gene Name

CA6

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Seborrhoeic dermatitis [ICD-11: EA81]

Function

Its role in saliva is unknown. Reversible hydration of carbon dioxide.

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BioChemical Class

Alpha-carbonic anhydrase

UniProt ID

CAH6_HUMAN

EC Number

EC 4.2.1.1

Sequence

MRALVLLLSLFLLGGQAQHVSDWTYSEGALDEAHWPQHYPACGGQRQSPINLQRTKVRYN
PSLKGLNMTGYETQAGEFPMVNNGHTVQISLPSTMRMTVADGTVYIAQQMHFHWGGASSE
ISGSEHTVDGIRHVIEIHIVHYNSKYKSYDIAQDAPDGLAVLAAFVEVKNYPENTYYSNF
ISHLANIKYPGQRTTLTGLDVQDMLPRNLQHYYTYHGSLTTPPCTENVHWFVLADFVKLS
RTQVWKLENSLLDHRNKTIHNDYRRTQPLNHRVVESNFPNQEYTLGSEFQFYLHKIEEIL
DYLRRALN

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3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

Salicyclic acid

Drug Info

Approved

Seborrhoeic dermatitis

[2], [3], [4]

Sulfamylon

Drug Info

Approved

Bacterial infection

[4], [5]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

Curcumin

Drug Info

Phase 3

Solid tumour/cancer

[6], [7]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 36 Inhibitor drugs

Salicyclic acid

Drug Info

[10]

Sulfamylon

Drug Info

[1]

Curcumin

Drug Info

[11]

PARABEN

Drug Info

[12]

FERULIC ACID

Drug Info

[12]

SPERMINE

Drug Info

[13]

2,4-Disulfamyltrifluoromethylaniline

Drug Info

[1]

2-Amino-benzenesulfonamide

Drug Info

[1]

2-hydrazinylbenzenesulfonamide

Drug Info

[1]

4-(2-aminopyrimidin-4-ylamino)benzenesulfonamide

Drug Info

[1]

4-(2-Hydroxy-ethyl)-benzenesulfonamide

Drug Info

[1]

4-(hydroxymethyl)benzenesulfonamide

Drug Info

[1]

4-Amino-3-bromo-benzenesulfonamide

Drug Info

[1]

4-Amino-3-fluoro-benzenesulfonamide

Drug Info

[1]

4-Amino-3-iodo-benzenesulfonamide

Drug Info

[1]

4-CYANOPHENOL

Drug Info

[10]

4-Hydrazino-benzenesulfonamide

Drug Info

[1]

6-(aminomethyl)-2H-chromen-2-one

Drug Info

[14]

6-(hydroxymethyl)-2H-chromen-2-one

Drug Info

[14]

6-Hydroxy-benzothiazole-2-sulfonic acid amide

Drug Info

[1]

7-butoxy-2H-chromen-2-one

Drug Info

[14]

7-propoxy-2H-chromen-2-one

Drug Info

[14]

BENZOLAMIDE

Drug Info

[1]

Carzenide

Drug Info

[1]

COUMARIN

Drug Info

[14]

Decane-1,10-diyl disulfamate

Drug Info

[15]

Decyl sulfamate

Drug Info

[15]

ELLAGIC ACID

Drug Info

[12]

Ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate

Drug Info

[14]

Hexane-1,6-diamine

Drug Info

[13]

N1-(2-aminoethyl)ethane-1,2-diamine

Drug Info

[13]

Octane-1,8-diyl disulfamate

Drug Info

[15]

Octyl sulfamate

Drug Info

[15]

P-Coumaric Acid

Drug Info

[12]

Pentane-1,5-diamine

Drug Info

[13]

Syringic Acid

Drug Info

[12]

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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). 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 Tissue Distribution 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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

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 Tissue Distribution

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Nitrogen metabolism	hsa00910	Affiliated Target
Class: Metabolism => Energy metabolism	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 Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Nitrogen metabolism

Reactome

[+] 1 Reactome Pathways

Reversible hydration of carbon dioxide

WikiPathways

[+] 1 WikiPathways

Reversible Hydration of Carbon Dioxide

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV. J Med Chem. 2009 Feb 12;52(3):646-54.

REF 2

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: 4306).

REF 3

Drug information of Salicyclic acid, 2008. eduDrugs.

REF 4

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

REF 5

ClinicalTrials.gov (NCT00634166) Prospective Evaluation of the Effects of Topical Therapy With Sulfamylon For 5% Topical Solution on Autograft Healing in Subjects With Thermal Injuries Requiring Meshed Autografts: A Comparison to a Historical Control Group. U.S. National Institutes of Health.

REF 6

REF 7

Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68.

REF 8

Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer. Expert Rev Anticancer Ther. 2011 Feb;11(2):179-83.

REF 9

ClinicalTrials.gov (NCT02984683) Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer. U.S. National Institutes of Health.

REF 10

Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.

REF 11

Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.

REF 12

Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.

REF 13

Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22.

REF 14

Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. J Med Chem. 2010 Jan 14;53(1):335-44.

REF 15

Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-sulfamate adducts with isozymes II and IX as a platform for designing tight-bi... J Med Chem. 2009 Oct 8;52(19):5990-8.

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