Nature - USA (2020-02-13)

Article

N N

O O

O O

HO OH

N N

O O

O O

MMV009085

MMV009085derivative

O O

HO CH 2 OH

HO OH

HN

OH

H

O

O

OH

O

Cytochalasin B

C3361

Extended Data Fig. 7 | Small-molecule-inhibition analysis of Pf HT1.
a, Surface transversal cross-sections through the membrane of the Pf HT1
structure in the occluded conformation with d-glucose shown as sticks, and a
side vestibule accessible to the C3- and C4-hydoxyl groups that—in human
GLUT3—was occupied by a monoolein lipid. b, The competitive uptake of
[^14 C]d-glucose (black bars) by Pf HT1 wild type and the mutant W412A in
proteoliposomes in the absence and presence of cytochalasin B (Cyb) (120 μM),

MMV009085 (MMV) (100 μM) or C3361 (100 μM). Error bars represent s.e.m. of

n = 3 biologically independent experiments (left). Cytochalasin B and the

inhibitor C3361 (which is d-glucose with a undec-10-en chain at the C3-hydroxyl

position) are shown (right). c, IC 50 curves for MMV009085 (blue filled circles)

and derivative lacking the butanol tails (grey filled circles). Error bars represent

s.e.m. of n = 3 biologically independent experiments (left). Structures of

MMV009085 and derivative are shown on the right.