Human Receptors Annotated Library

Description

•Receptors regulate various biological phenomena, including growth, development, metabolism, the immune system, and homeostasis.

•Physiologically the receptor signaling engagement can be modulated by small molecules that mimic and/or compete with natural ligands of receptors, e.g. steroids, retinoic acid, vitamin D

•Receptors are well recognized as important therapeutic targets for

-Oncology, e.g. Breast cancer, prostate cancer, acute propyelocytic leukemia (APL)
-CNS, e.g. Sleep disorders, addiction, Alzheimer’s disease, retinal degeneration
-Cardiovascular system, e.g. Pulmonary hypertension, fibrosis, cholestatic regulation

A unique collection of small molecule compounds with annotated activities for Receptors targets

• Annotated activities : 51 receptors targets (excluded GPCRs, Ion Channels, Kinases, Phosphatases, and Proteases)
• Express Delivery : 640 compounds
• Complete Version : 5600 compounds

Related

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
Y042-7692	Q92731	Estrogen receptor beta	IC50	=	98.7	nM			US-8552057-B2	Estrogen receptor beta	Binding Assay: The binding affinity and selectivity of candidate molecules (PanVera Corp.).
Y040-0960	P03372	Estrogen receptor alpha	IC50	=	2320	nM			US-8552057-B2	Estrogen receptor	Binding Assay: The binding affinity and selectivity of candidate molecules (PanVera Corp.).
3882-1710	O60706	Sulfonylurea receptor 2 Kir6.2	Ki	=	130	nM	9464357	10.1021/jm970762d		ATP-binding cassette sub-family C member 9	Binding affinity was determined by displacement of [3H]P1075 from its binding sites in canine cardiac membranes
3882-1710	O60706	Sulfonylurea receptor 2 Kir6.2	IC50	=	220	nM	11356099	10.1021/jm000484+		ATP-binding cassette sub-family C member 9	Inhibition of human SUR2A/Kir6.2 expressed in Xenopus oocytes
8017-2388	P35869	Aryl hydrocarbon receptor	EC50	=	583.2	nM				Aryl hydrocarbon receptor	PUBCHEM_BIOASSAY: Luminescence-based cell-based high throughput dose response assay for activators of the Aryl Hydrocarbon Receptor (AHR).
2361-0083	P10275	Androgen Receptor	IC50	=	3.9	nM	15456242	10.1021/jm0342515		Androgen receptor	Inhibition of human androgen receptor expressed in Escherichia coli
7165-0212	P24468	COUP transcription factor 2	IC50	=	2750	nM				COUP transcription factor 2	PubChem BioAssay. Luminescence-based cell-based high throughput dose response assay to identify inhibitors of COUP-TFII (NR2F2).   (Class of assay: confirmatory)
6550-0048	Q9NR96	Toll-like receptor 9	IC50	=	3122	nM				Toll-like receptor 9	PUBCHEM_BIOASSAY: Fluorescence-based cell-based high throughput dose response assay for inhibitors of TLR9-MyD88 binding.

Publications

1.J. Med. Chem. 2003 46(24):5258-5270 Rational design and synthesis of androgen receptor-targeted nonsteroidal anti-androgen ligands for the tumor-specific delivery of a doxorubicin-formaldehyde conjugate. Cogan PS Koch TH.

2.Proc. Natl. Acad. Sci. U.S.A. 2007 104(29):11927-11932 Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Bisson WH Cheltsov AV Bruey-Sedano N Lin B Chen J Goldberger N May LT Christopoulos A Dalton JT Sexton PM Zhang XK Abagyan R.

3.J. Med. Chem. 2014 57(3):849-860 Glucocorticoid receptor modulators informed by crystallography lead to a new rationale for receptor selectivity function and implications for structure-based design. Carson MW Luz JG Suen C Montrose C Zink R Ruan X Cheng C Cole H Adrian MD Kohlman DT Mabry T Snyder N Condon B Maletic M Clawson D Pustilnik A Coghlan MJ.

4.Bioorg. Med. Chem. Lett. 2016 26(10):2459-2463 Discovery of biaryls as RORγ inverse agonists by using structure-based design. Enyedy IJ Powell NA Caravella J van Vloten K Chao J Banerjee D Marcotte D Silvian L McKenzie A Hong VS Fontenot JD.

5.ACS Med. Chem. Lett. 2012 3(12):1054-1058 From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design. Yu LF Zhang HK Gunosewoyo H Kozikowski AP.

6.Bioorg. Med. Chem. Lett. 2014 24(9):2021-2032 Antagonists of the kappa opioid receptor. Urbano M Guerrero M Rosen H Roberts E.

7.MedChemComm 2013 4(5):764-776 Synthetic modulators of the retinoic acid receptor-related orphan receptors. Kamenecka TM Lyda B Chang MR Griffin PR.

8.MedChemComm 2013 4(11):1439-1442 The A-CD analogue of 1617-estriol is a potent and highly selective estrogen receptor agonist. Sauvee C Schafer A Sunden H Ma J Gustavsson A Burstein ES Olsson R

9.J. Med. Chem. 2008 51(8):2481-2491 Virtual fragment linking: an approach to identify potent binders from low affinity fragment hits. Crisman TJ Bender A Milik M Jenkins JL Scheiber J Sukuru SC Fejzo J Hommel U Davies JW Glick M.

10.Bioorg. Med. Chem. Lett. 2015 25(2):270-275 Biological evaluation and structural insights for design of subtype-selective peroxisome proliferator activated receptor-α (PPAR-α) agonists. Gangwal RP Damre MV Das NR Sharma SS Sangamwar AT.