TY - JOUR
T1 - Designing selective inhibitors for calcium-dependent protein kinases in apicomplexans
AU - Hui, Raymond
AU - El Bakkouri, Majida
AU - Sibley, L. David
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/6/26
Y1 - 2015/6/26
N2 - Apicomplexan parasites cause some of the most severe human diseases, including malaria (caused by Plasmodium), toxoplasmosis, and cryptosporidiosis. Treatments are limited by the lack of effective drugs and development of resistance to available agents. By exploiting novel features of protein kinases in these parasites, it may be possible to develop new treatments. We summarize here recent advances in identifying small molecule inhibitors against a novel family of plant-like, calcium-dependent kinases that are uniquely expanded in apicomplexan parasites. Analysis of the 3D structure, activation mechanism, and sensitivity to small molecules had identified several attractive chemical scaffolds that are potent and selective inhibitors of these parasite kinases. Further optimization of these leads may yield promising new drugs for treatment of these parasitic infections.
AB - Apicomplexan parasites cause some of the most severe human diseases, including malaria (caused by Plasmodium), toxoplasmosis, and cryptosporidiosis. Treatments are limited by the lack of effective drugs and development of resistance to available agents. By exploiting novel features of protein kinases in these parasites, it may be possible to develop new treatments. We summarize here recent advances in identifying small molecule inhibitors against a novel family of plant-like, calcium-dependent kinases that are uniquely expanded in apicomplexan parasites. Analysis of the 3D structure, activation mechanism, and sensitivity to small molecules had identified several attractive chemical scaffolds that are potent and selective inhibitors of these parasite kinases. Further optimization of these leads may yield promising new drugs for treatment of these parasitic infections.
KW - ATP-binding pocket
KW - chemotherapy
KW - gatekeeper
KW - orthogonal inhibitors
KW - parasites
KW - serine-threonine protein kinases
UR - http://www.scopus.com/inward/record.url?scp=84932194861&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2015.04.011
DO - 10.1016/j.tips.2015.04.011
M3 - Review article
C2 - 26002073
AN - SCOPUS:84932194861
VL - 36
SP - 452
EP - 460
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
SN - 0165-6147
IS - 7
ER -