Human Ion Channels Annotated Library
Description
• Physiologically the Ion Channels are regulated by
– voltage, e.g. most Na, K, Ca and some Cl channels are “voltage-gated ion channels”– intracellular and/or extracellular mediators, e.g. some K and Cl channels, TRP channels, GABA(A) andP2X receptors are “ligand-gated ion channels”
– the central nervous system (CNS), e.g. sleep disorders, anxiety, epilepsy, pain– the peripheral nervous system, e.g. anticonvulsant, analgesic, anti-inflammatory– the cardiovascular system, e.g. ischemia, hypoxic conditions, stroke
❑ Annotated activities : 86 ion channels targets❑ Express Delivery : 320 compounds❑ Complete Version : 394 compounds
Library Composition
Data sources of annotations : Pharos, ChEMBL 25, PubChem, PubMed, Current Patent Literature (CAS, Integrity)
IDNUMBER – ChemDiv Catalog ID (in some instances the same IDNUMBER might have multiple annotation entries due to multiple data sources or because having activity against multiple similar targets);
UNIPROT – SwissProt and ChEMBL Target accesion ID;
Type – character of the measured activity;
Value – Active compounds selection criteria, included only compounds with reported activities < 5 µM;
pubmed_id – PubMed record entry;
doi, patent_id – journal or patent reference to a publication of original data;
For screening data extracted from PubChem, see column assay_description for entry names PUBCHEM_BIOASSAY
Example of Annotations - an Excel file structure
|
IDNUMBER |
UNIPROT |
Target Name |
Type |
Relation |
Value |
Units |
pubmed_id |
doi |
patent_id |
Target Description |
assay_description |
|
8005-3627 |
P36544 |
Neuronal acetylcholine receptor protein alpha-7 subunit |
Ki |
= |
120 |
nM |
|
|
US-8541447-B2 |
Neuronal acetylcholine receptor subunit alpha-7 |
Binding Assay: Binding assay using alpha 7 nAChR. |
|
3882-1710 |
Q14654 |
Sulfonylurea receptor 2 Kir6.2 |
Ki |
= |
130 |
nM |
9464357 |
10.1021/jm970762d |
|
ATP-sensitive inward rectifier potassium channel 11 |
Binding affinity was determined by displacement of [3H]P1075 from its binding sites in canine cardiac membranes |
|
4120-0157 |
P14867 |
GABA-A receptor; alpha-1/beta-2/gamma-2 |
EC50 |
= |
1200 |
nM |
12646036 |
10.1021/jm020465v |
|
Gamma-aminobutyric acid receptor subunit alpha-1 |
Ability to enhance currents from alpha-1-beta-2-gamma-2L-subunit of GABA receptor elicited by low concentrations of GABA |
|
6264-0421 |
Q05586 |
Glutamate [NMDA] receptor |
IC50 |
= |
600 |
nM |
1433216 |
10.1021/jm00100a019 |
|
Glutamate receptor ionotropic NMDA 1 |
Inhibition of [3H]1 binding to dextromethorpin binding site of guinea pig microsomal pellet P3 N-methyl-D-aspartate glutamate receptor |
|
6264-0421 |
Q12809 |
HERG |
IC50 |
= |
1470 |
nM |
21300721 |
10.1093/cvr/cvr044 |
|
Potassium voltage-gated channel subfamily H member 2 |
Inhibition of hERG K channel |
|
R090-0022 |
P46098 |
Serotonin 3 (5-HT3) receptor |
Ki |
= |
2500 |
nM |
8831767 |
10.1021/jm9603936 |
|
5-hydroxytryptamine receptor 3A |
Compound was tested for the inhibition of [3H]GR-65630 binding to 5-hydroxytryptamine 3 receptor expressed in NG 108-15 cells |
|
0106-0141 |
Q99572 |
P2X purinoceptor 7 |
Kd |
= |
79.43 |
nM |
14592505 |
10.1016/j.bmcl.2003.08.034 |
|
P2X purinoceptor 7 |
Antagonistic activity against the P2X7 ion channel |
|
3389-0874 |
Q8TDD5 |
MCOLN3 protein |
EC50 |
= |
1450 |
nM |
|
|
|
Mucolipin-3 |
PUBCHEM_BIOASSAY: Dose response cell-based high-throughput screening assay for agonists of the transient receptor potential channel ML3 (TRPML3). |
Publications
1.Bioorg Med Chem Lett. 2010 20(23):7076-9. 5-benzyloxytryptamine as an antagonist of TRPM8. DeFalco J, Steiger D, Dourado M, Emerling D, Duncton MA.
2.J Med Chem. 2005 48(1):71-90. Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides. Doherty EM, Fotsch C, Bo Y, Chakrabarti PP, Chen N, Gavva N, Han N, Kelly MG, Kincaid J, Klionsky L, Liu Q, Ognyanov VI, Tamir R, Wang X, Zhu J, Norman MH, Treanor JJ.
3.J Med Chem. 2006 49(8):2526-33. 4-quinolone derivatives: high-affinity ligands at the benzodiazepine site of brain GABA A receptors. synthesis, pharmacology, and pharmacophore modeling. Lager E, Andersson P, Nilsson J, Pettersson I, Nielsen EØ, Nielsen M, Sterner O, Liljefors T.
4.J Med Chem. 1996 39(20):4017-26. Structure-activity relationships for the binding of arylpiperazines and arylbiguanides at 5-HT3 serotonin receptors. Dukat M, Abdel-Rahman AA, Ismaiel AM, Ingher S, Teitler M, Gyermek L, Glennon RA.
5.Bioorg Med Chem Lett. 2017 27(16):3931-3938. Discovery and development of a novel class of phenoxyacetyl amides as highly potent TRPM8 agonists for use as cooling agents. Noncovich A, Priest C, Ung J, Patron AP, Servant G, Brust P, Servant N, Faber N, Liu H, Gonsalves NS, Ditschun TL.
6.J Med Chem. 2015 58(7):2958-2966. Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor α1 for the treatment of pain. Wells MM, Tillman TS, Mowrey DD, Sun T, Xu Y, Tang P.
7.J Med Chem. 2005 48(23):7496-9. Random chemistry as a new tool for the generation of small compound libraries: development of a new acetylcholinesterase inhibitor. Kapková P, Heller E, Unger M, Folkers G, Holzgrabe U.
8.J Med Chem. 2016 59(18):8398-411. Preparation, Antiepileptic Activity, and Cardiovascular Safety of Dihydropyrazoles as Brain-Penetrant T-Type Calcium Channel Blockers. Remen L, Bezençon O, Simons L, Gaston R, Downing D, Gatfield J, Roch C, Kessler M, Mosbacher J, Pfeifer T, Grisostomi C, Rey M, Ertel EA, Moon R.