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CaCC

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Target id: 708

Nomenclature: CaCC

Family: Calcium activated chloride channel (CaCC)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 10 986 11q13.3 ANO1 anoctamin 1
Mouse 10 960 7 F5 Ano1 anoctamin 1, calcium activated chloride channel
Rat - - 1q42 Ano1 anoctamin 1
Previous and Unofficial Names Click here for help
DOG1 | ORAOV2 | TAOS2 | TMEM16A | oral cancer overexpressed 2 | transmembrane protein 16A | anoctamin 1, calcium activated chloride channel | anoctamin 1
Database Links Click here for help
Alphafold Q5XXA6 (Hs), Q8BHY3 (Mm)
ChEMBL Target CHEMBL2046267 (Hs), CHEMBL4105874 (Mm)
DrugBank Target Q5XXA6 (Hs)
Ensembl Gene ENSG00000131620 (Hs), ENSMUSG00000031075 (Mm), ENSRNOG00000020865 (Rn)
Entrez Gene 55107 (Hs), 101772 (Mm), 309135 (Rn)
Human Protein Atlas ENSG00000131620 (Hs)
KEGG Gene hsa:55107 (Hs), mmu:101772 (Mm), rno:309135 (Rn)
OMIM 610108 (Hs)
Pharos Q5XXA6 (Hs)
UniProtKB Q5XXA6 (Hs), Q8BHY3 (Mm)
Wikipedia ANO1 (Hs)
Functional Characteristics Click here for help
γ = 0.5-5 pS; permeability sequence, SCN- > NO3 -> I- > Br- > Cl- > F-; relative permeability of SCN-:Cl- ~8. I-:Cl- ~3, aspartate:Cl- ~0.15, outward rectification (decreased by increasing [Ca2+]i); sensitivity to activation by [Ca2+]i decreased at hyperpolarized potentials; slow activation at positive potentials (accelerated by increasing [Ca2+]i); rapid deactivation at negative potentials, deactivation kinetics modulated by anions binding to an external site; modulated by redox status
Natural/Endogenous Ligands Click here for help
Ca2+
Ins(3,4,5,6)P4

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
PAM_16A Small molecule or natural product Hs Activation 8.4 pEC50 - no 1
⤷ pEC50 8.4 (EC50 3.6x10-9 M) [1]
Not voltage dependent
intracellular Ca2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Activation - - - no
⤷
Not voltage dependent
Eact Small molecule or natural product Hs Activation - - - no 9
⤷ [9]
Not voltage dependent
Activator Comments
As a positive allosteric modulator PAM_16A can be considered as a CaCC 'activator'.
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
TMinh-23 Small molecule or natural product Hs Inhibition 7.5 pIC50 - no 8
⤷ pIC50 7.5 (IC50 3x10-8 M) [8]
Not voltage dependent
MONNA Small molecule or natural product Hs Inhibition 7.1 pIC50 - no 2,4,8
⤷ pIC50 7.1 (IC50 8x10-8 M) [2,4,8]
Not voltage dependent
Description: Inhibition of TMEM16A current in Xenopus laevis oocytes by voltage-clamp assay.
Ani9 Small molecule or natural product Hs Inhibition 7.0 pIC50 - no 6
⤷ pIC50 7.0 (IC50 1.07x10-7 M) [6]
Not voltage dependent
Description: Inhibition of activator-induced current via human ANO1 stably expressed in Fischer rat thyroid (FRT) cells.
T16Ainh-A01 Small molecule or natural product Hs Inhibition ~6.0 pIC50 - no 2,5
⤷ pIC50 ~6.0 (IC50 ~1x10-6 M) [2,5]
Not voltage dependent
Description: Inhibition of TMEM16A-mediated chloride current in FRT cells
crofelemer Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.2 pIC50 - no 7
⤷ pIC50 5.2 (IC50 6.5x10-6 M) [7]
Not voltage dependent
fluoxetine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition - - - no
⤷
Not voltage dependent
niflumic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition - - - no
⤷
Not voltage dependent
flufenamic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition - - - no
⤷
Not voltage dependent
mibefradil Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition - - - no
⤷
Not voltage dependent
9-anthroic acid Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - - no
⤷
Not voltage dependent
DCDPC Small molecule or natural product Hs Inhibition - - - no
⤷
Not voltage dependent
DIDS Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - - no
⤷
Not voltage dependent
Ins(3,4,5,6)P4 Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Hs Inhibition - - - no
⤷
Not voltage dependent
NPPB Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition - - - no
⤷
Not voltage dependent
SITS Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - - no
⤷
Not voltage dependent
tannic acid Small molecule or natural product Hs Inhibition - - - no
⤷
Not voltage dependent
CaCCinh-A01 Small molecule or natural product Hs Inhibition - - - no 2-3
⤷ [2-3]
Not voltage dependent

References

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1. Al-Hosni R, Agostinelli E, Ilkan Z, Scofano L, Kay R, Dinsdale RL, Acheson K, MacDonald A, Rivers D, Biosa A et al.. (2025) Pharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function. BJP,. DOI: 10.1111/bph.17383

2. Boedtkjer DM, Kim S, Jensen AB, Matchkov VM, Andersson KE. (2015) New selective inhibitors of calcium-activated chloride channels - T16A(inh) -A01, CaCC(inh) -A01 and MONNA - what do they inhibit?. Br J Pharmacol, 172 (16): 4158-72. [PMID:26013995]

3. De La Fuente R, Namkung W, Mills A, Verkman AS. (2008) Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel. Mol Pharmacol, 73 (3): 758-68. [PMID:18083779]

4. Oh SJ, Hwang SJ, Jung J, Yu K, Kim J, Choi JY, Hartzell HC, Roh EJ, Lee CJ. (2013) MONNA, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1. Mol Pharmacol, 84 (5): 726-35. [PMID:23997117]

5. Piechowicz KA, Truong EC, Javed KM, Chaney RR, Wu JY, Phuan PW, Verkman AS, Anderson MO. (2016) Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1. J Enzyme Inhib Med Chem, 31 (6): 1362-8. [PMID:26796863]

6. Seo Y, Lee HK, Park J, Jeon DK, Jo S, Jo M, Namkung W. (2016) Ani9, A Novel Potent Small-Molecule ANO1 Inhibitor with Negligible Effect on ANO2. PLoS One, 11 (5): e0155771. [PMID:27219012]

7. Tradtrantip L, Namkung W, Verkman AS. (2010) Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol, 77 (1): 69-78. [PMID:19808995]

8. Truong EC, Phuan PW, Reggi AL, Ferrera L, Galietta LJV, Levy SE, Moises AC, Cil O, Diez-Cecilia E, Lee S et al.. (2017) Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A). J Med Chem, 60 (11): 4626-4635. [PMID:28493701]

9. Verkman AS, Namkung W. (2017) Small molecule activators of calcium-activated chloride channels and methods of use. Patent number: US9790218B2. Assignee: University of California. Priority date: 03/08/2012. Publication date: 17/10/2017.

Contributors

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