Imperial College London
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DR COEN WIEGMAN

Faculty of Medicine, National Heart & Lung Institute

Senior Teaching Fellow
 
 
 
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Contact

 

+44 (0)20 7594 1980c.wiegman

 
 
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Location

 

305Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@inproceedings{Wiegman:2015:10.1089/jamp.2015.ab01.abstracts,
author = {Wiegman, CH and Adcock, IM and Rothaul, A and Main, M and Morgan, F},
doi = {10.1089/jamp.2015.ab01.abstracts},
pages = {A23--A23},
publisher = {Mary Ann Liebert},
title = {IN VITRO EVALUATION OF A NEW POTENT, SELECTIVE PAN-JANUS KINASE (JAK) INHIBITOR VR588},
url = {http://dx.doi.org/10.1089/jamp.2015.ab01.abstracts},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - CPAPER
AB  - Rationale: VR588 is promising pan-JAK inhibitor suited to inhalationdelivery. These studies were designed to characterise the invitrokinase inhibition profile of VR588 and to determine its selectivityversus non-JAK kinases.Methods: Kinase activity was assessed in a non-cell (Z’Lyte Florescence assay) and in cell based assays using stimulation of humanwhole blood (IL-2 stimulated INFc production and JAK1/JAK3and pSTATa/b activation and IL-6 stimulated pSTAT3 to assessJAK1, JAK2 and Tyk2 activity). Selectivity of VR588 (1 mM) againsta panel of 93 human kinases was also assessed.Results: VR588 potently inhibited JAK 1, 2, 3 and Tyk2 kinases(IC50 4.2, 0.7, 2.1 & 6 nM respectively) in the non-cell based assay andshowed poor inhibitory activity against non –JAK kinases FLT3,PDGFB, JNK2 and Syk (IC50 247, 2350,4000, 8900 nM respectively).JAK inhibition was confirmed in the cell based assays with inhibition ofIL-2 stimulated INFc, IL-2 stimulated pSTATa/b & IL-6 stimulatedpSTAT3 demonstrating IC50 values of 209, 29 & 62 nM respectively.Selectivity versus human kinases revealed no relevant off- target effects.Conclusions: VR588 represents a potent, selective and balancedpan-JAK inhibitor, suggesting VR588 may have utility as a treatmentfor asthma and COPD.
AU  - Wiegman,CH
AU  - Adcock,IM
AU  - Rothaul,A
AU  - Main,M
AU  - Morgan,F
DO  - 10.1089/jamp.2015.ab01.abstracts
EP  - 23
PB  - Mary Ann Liebert
PY  - 2015///
SN  - 1941-2711
SP  - 23
TI  - IN VITRO EVALUATION OF A NEW POTENT, SELECTIVE PAN-JANUS KINASE (JAK) INHIBITOR VR588
UR  - http://dx.doi.org/10.1089/jamp.2015.ab01.abstracts
UR  - http://hdl.handle.net/10044/1/29984
ER  -
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