CNS Annotated Library

Description

•Library of compounds acting on central nervous system (CNS) targets

•In CNS drug discovery the drug targets are used for targeting CNS and neurological related diseases like Parkinson’s disease, Alzheimer’s disease, schizophrenia, drug dependence, etc.

•Activity of drug target as a nucleic acid or a protein (e.g. an enzyme, a receptor) can be modulated by a small-molecular-weight chemical compound.

•As the discovery, identification, characterization and validation of novel human drug targets for CNS disease biology, and the emergence of new mechanisms and targets for misfolded proteins, tau, GCPRs, kinase inhibitors, neuroinflammation, etc. continues to grow; this library is a valuable tool for the neurological and CNS drug discovery.

A unique collection of small molecule compounds with annotated activities for protein targets relevant for the CNS therapeutic area

• Annotated activities : 72 CNS related protein targets
• Express Delivery : 480 compounds
• Complete Version : 733 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	assay_description	Relation	Value	Units	Type	pubmed_id	UNIPROT	Entry name	Protein names
H025-4101C	Displacement of [3H]N-alpha-methylhistamine from human H3 receptor expressed in HEK-293 cell membrane	=	11.48	nM	Ki	24650714	Q9Y5N1	HRH3_HUMAN	Histamine H3 receptor (H3R) (HH3R) (G-protein coupled receptor 97)
H025-3052	Antagonist activity at human recombinant 5HT6 receptor expressed in HEK293 cells	=	11.75	nM	Ki	21277782	P50406	5HT6R_HUMAN	5-hydroxytryptamine receptor 6 (5-HT-6) (5-HT6) (Serotonin receptor 6)
Y021-1623	Binding affinity towards 5-hydroxytryptamine 3 receptor	=	12	nM	Ki	12217367	P46098	5HT3A_HUMAN	5-hydroxytryptamine receptor 3A (5-HT3-A) (5-HT3A) (5-hydroxytryptamine receptor 3) (5-HT-3) (5-HT3R) (Serotonin receptor 3A) (Serotonin-gated ion channel receptor)
8016-5188	Displacement of [3H]Flumazenil from human GABA-Aalpha1 receptor plus beta-2-gamma-2 expressed in HEK293 cells	=	12	nM	Ki	16610795	P18507	GBRG2_HUMAN	Gamma-aminobutyric acid receptor subunit gamma-2 (GABA(A) receptor subunit gamma-2)
G229-0078	Positive allosteric modulation of human mGluR5 expressed in HEK293A cells	=	12.5	nM	EC50	22832311	P41594	GRM5_HUMAN	Metabotropic glutamate receptor 5 (mGluR5)
8016-5188	Binding affinity to the benzodiazepine receptor assayed using 0.5 nM [3H]flunitrazapam as radioligand in guinea pig cerebellum	=	14.1	nM	IC50		P14867	GBRA1_HUMAN	Gamma-aminobutyric acid receptor subunit alpha-1 (GABA(A) receptor subunit alpha-1)
1000-0591	Displacement of [3H]-CP-55940 from human CB2 receptor expressed in HEK293 cell membranes	=	16.8	nM	Ki	27448919	P34972	CNR2_HUMAN	Cannabinoid receptor 2 (CB-2) (CB2) (hCB2) (CX5)
H025-0190C	Binding affinity to adrenergic alpha1A receptor by radioligand displacement assay	=	19.05	nM	Ki	19945877	P35348	ADA1A_HUMAN	Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c)
H025-3231	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LRRK2	=	19.95	nM	Ki		Q5S007	LRRK2_HUMAN	Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin)

Publications

1.Eur. J. Med. Chem. 2010(45)2:782-789. 8-Sulfonyl-substituted tetrahydro-1H-pyrido[43-b]indoles as 5-HT6 receptor antagonists. Ivachtchenko AV Mitkin OD Tkachenko SE Okun IM Kysil VM.

2.Bioorg. Med. Chem. Lett. 2010(20)1:78-82. Synthesis and biological activity of 5-styryl and 5-phenethyl-substituted 2345-tetrahydro-1H-pyrido[43-b]indoles. Ivachtchenko AV Frolov EB Mitkin OD Tkachenko SE Okun IM Khvat AV.

3.Bioorg. Med. Chem. Lett. 2005(15)22:4889-4897. 35-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Coe JW Brooks PR Wirtz MC Bashore CG Bianco KE Vetelino MG Arnold EP Lebel LA Fox CB Tingley FD Schulz DW Davis TI Sands SB Mansbach RS Rollema H O'Neill BT.

4.Bioorg. Med. Chem. Lett. 2010(20)16:4749-4752. A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists. Lowe JA DeNinno SL Coe JW Zhang L Mente S Hurst RS Mather RJ Ward KM Shrikhande A Rollema H Johnson DE Horner W Gorczyca R Tingley FD Kozak R Majchrzak MJ Tritto T Sadlier J Shaffer CL Ellerbrock B Osgood SM MacDougall MC McDowell LL.

5.J. Med. Chem. 2009(52)13:3855-3868. 5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity. Pierson PD Fettes A Freichel C Gatti-McArthur S Hertel C Huwyler J Mohr P Nakagawa T Nettekoven M Plancher JM Raab S Richter H Roche O Rodríguez Sarmiento RM Schmitt M Schuler F Takahashi T Taylor S Ullmer C Wiegand R.

6.J. Med. Chem. 2008(51)21:6889-6901. Synthesis and evaluation of structurally constrained quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists. Nagase T Mizutani T Sekino E Ishikawa S Ito S Mitobe Y Miyamoto Y Yoshimoto R Tanaka T Ishihara A Takenaga N Tokita S Sato N.

7.Substituted cycloalcano[e and d] pyrazolo [15-a]pyrimidines/antagonists of serotonin 5-HT6 receptors and methods for production and the use thereof US-8629154-B2 2014

8.Bioorg. Med. Chem. Lett. 2009(19)12:3214-3216. Identification of a novel series of 3-piperidinyl-5-sulfonylindazoles as potent 5-HT6 ligands. Liu KG Lo JR Comery TA Zhang GM Zhang JY Kowal DM Smith DL Di L Kerns EH Schechter LE Robichaud AJ.

9.J. Med. Chem. 2011(54)23:8161-8173. Synthesis and structure-activity relationship (SAR) of (57-disubstituted 3-phenylsulfonyl-pyrazolo[15-a]pyrimidin-2-yl)-methylamines as potent serotonin 5-HT(6) receptor (5-HT(6)R) antagonists. Ivachtchenko AV Golovina ES Kadieva MG Kysil VM Mitkin OD Tkachenko SE Okun IM.