Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26934697
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2016 ; 11
(3
): e0149996
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against
14,000 Cell-Active Compounds
#MMPMID26934697
Crowther GJ
; Hillesland HK
; Keyloun KR
; Reid MC
; Lafuente-Monasterio MJ
; Ghidelli-Disse S
; Leonard SE
; He P
; Jones JC
; Krahn MM
; Mo JS
; Dasari KS
; Fox AM
; Boesche M
; El Bakkouri M
; Rivas KL
; Leroy D
; Hui R
; Drewes G
; Maly DJ
; Van Voorhis WC
; Ojo KK
PLoS One
2016[]; 11
(3
): e0149996
PMID26934697
show ga
In 2010 the identities of thousands of anti-Plasmodium compounds were released
publicly to facilitate malaria drug development. Understanding these compounds'
mechanisms of action--i.e., the specific molecular targets by which they kill the
parasite--would further facilitate the drug development process. Given that
kinases are promising anti-malaria targets, we screened ~14,000 cell-active
compounds for activity against five different protein kinases. Collections of
cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos
Antimalarial Set, or TCAMS), St. Jude Children's Research Hospital (260
compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box)
were screened in biochemical assays of Plasmodium falciparum calcium-dependent
protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2
(MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent
inhibitors (IC50 < 1 ?M) were discovered for three of the kinases: CDPK1, CDPK4,
and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme
and deserve further scrutiny. Additionally, kinome-wide competition assays
revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases,
and several related compounds that inhibit CDPK1 and CDPK4 yet have limited
cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple
Plasmodium kinase targets without harming human cells is challenging but
feasible.