Human Kinases Annotated Library

Description

•Kinases are enzymatic proteins that phosphorylate other functional proteins

•Physiologically the kinase enzymatic activity can be modulated by

- Catalytic ATP site binders
- Allosteric binders that cause conformational changes within the catalytic ATP site

•Kinases are well recognized as important therapeutic targets for

- Oncology, e.g. cancer immunotherapy
- Inflammatory diseases, e.g. fibrosis, rheumatoid arthritis
- Cardiovascular system, e.g. cerebral vasospasm, pulmonary arterial hypertension

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

• Annotated activities : 249 kinase targets
• Express Delivery : 640 compounds
• Complete Version : 2585 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
8008-7025	Q7L7X3	Serine/threonine-protein kinase TAO1	IC50	<	50	nM			US-20070208166-A1	Serine/threonine-protein kinase TAO1	Inhibition of human KIAA1361 kinase domain
5122-1774	P43250	G protein-coupled receptor kinase 6	IC50	=	1030	nM			US-20140309185-A1	G protein-coupled receptor kinase 6	Inhibition of human recombinant full-length GST-tagged human GRK6
0073-0059	O75460	Serine/threonine-protein kinase/endoribonuclease IRE1	IC50	=	170	nM			US-8614253-B2	Serine/threonine-protein kinase/endoribonuclease IRE1	In Vitro Enzyme Assays: IRE-1 alpha T1 RNase and RNase A assays
S553-1690	Q00535	Cyclin-dependent kinase 5	Ki	=	50.12	nM				Cyclin-dependent-like kinase 5	PUBCHEM_BIOASSAY: Navigating the Kinome.
Y031-8414	P50613	Cyclin-dependent kinase 7/ cyclin H	IC50	=	400	nM	20627564	10.1016/j.bmcl.2010.05.039		Cyclin-dependent kinase 7	Inhibition of human CDK7/Cyclin H/MAT1
L785-0049	P49336	CDK8/Cyclin C	IC50	=	9	nM	28231524	10.1016/j.ejmech.2017.02.020		Cyclin-dependent kinase 8	Inhibition of Alexa647 tracer binding to full length recombinant human His-tagged CDK8/Cyclin C
H025-3231	Q2M2I8	Adaptor-associated kinase	Kd	=	1200	nM	22037378	10.1038/nbt.1990		AP2-associated protein kinase 1	Binding constant for AAK1 kinase domain
8012-7305	Q5S007	Leucine-rich repeat serine/threonine-protein kinase 2	IC50	=	100	nM	28774425	10.1016/j.bmcl.2017.07.052		Leucine-rich repeat serine/threonine-protein kinase 2	Inhibition of LRRK2 (unknown origin) by HTRF assay

Publications

1.J Med Chem 2017 60(14):6337-6352. Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers. Sun QZ Lin GF Li LL Jin XT Huang LY Zhang G Yang W Chen K Xiang R Chen C Wei YQ Lu GW Yang SY.

2.Bioorg Med Chem Lett 2017 27(11):2617-2621. Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus. Shaw SJ Goff DA Lin N Singh R Li W McLaughlin J Baltgalvis KA Payan DG Kinsella TM.

3.J Med Chem 2017 60(16):7099-7107. Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models. Yamada K Levell J Yoon T Kohls D Yowe D Rigel DF Imase H Yuan J Yasoshima K DiPetrillo K Monovich L Xu L Zhu M Kato M Jain M Idamakanti N Taslimi P Kawanami T Argikar UA Kunjathoor V Xie X Yagi YI Iwaki Y Robinson Z Park HM.

4.J. Med. Chem. 2015 58(3):1563-1568. A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinases. Sharma LK Leonardi R Lin W Boyd VA Goktug A Shelat AA Chen T Jackowski S Rock CO.

5.ACS Med. Chem. Lett. 2014 5(9):963-967. Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4. Schmitt C Miralinaghi P Mariano M Hartmann RW Engel M.

6.J. Med. Chem. 2014 57(6):2755-2772. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. Salado IG Redondo M Bello ML Perez C Liachko NF Kraemer BC Miguel L Lecourtois M Gil C Martinez A Perez DI.

7.Nat. Biotechnol. 2011 29(11):1046-1051. Comprehensive analysis of kinase inhibitor selectivity. Davis MI Hunt JP Herrgard S Ciceri P Wodicka LM Pallares G Hocker M Treiber DK Zarrinkar PP.

8.Bioorg. Med. Chem. Lett. 2011 21(13):4108-4114. Identification of new inhibitors of protein kinase R guided by statistical modeling. Bryk R Wu K Raimundo BC Boardman PE Chao P Conn GL Anderson E Cole JL Duffy NP Nathan C Griffin JH.

9.ACS Med. Chem. Lett. 2011 2(2):154-159. Synthesis and Structure-Activity Relationships of Benzothienothiazepinone Inhibitors of Protein Kinase D. Bravo-Altamirano K George KM Frantz MC Lavalle CR Tandon M Leimgruber S Sharlow ER Lazo JS Wang QJ Wipf P.