| Efficacy |
Autism spectrum disorder (ASD) model: SERT
Ala56 mouse (ip
injection daily for 7 d) |
MW150 repeat administration
mitigates SERT Ala56-mediated 5-HT
receptor hypersensitivities and altered social interaction; reverses
SERT Ala56-mediated reductions in intestinal motility |
| |
APP/PS1 transgenic (oral gavage daily for 1–2
mos) |
Improved performance in contextual fear memory
and radial arm
water maze (RAWM) with no effect on sensory, motor, and motivational
mechanisms; no effects on open field tasks; dose-dependent efficacy
at 0.5–2.5 mM |
| |
APPNlh/Nlh/PS1P264L/P264L knock-in (KI)
(ip injection daily for 14 d) |
Improved performance in
RAWM |
| |
Tauopathy model: infusion
of synthetic 4R/2N human tau into
dorsal hippocampus (single ip injection of MW150) |
Attenuates
defects in associative memory (contextual fear learning
paradigm); attenuates defects in short-term spatial memory (RAWM);
no effect on sensory, motor, and motivational mechanisms; no effects
on open field tasks |
| |
Tauopathy
model: rTg4510 (human tau, P301L mutation) (oral
gavage daily for 45 d) |
Attenuates defects in associative
memory (contextual fear learning
paradigm); attenuates defects in short-term spatial memory (RAWM) |
| Pharmacodynamic end points |
Autism
spectrum disorder (ASD) model: SERT Ala56 mouse |
MW150
repeat administration normalizes 5-HT clearance in SERT
Ala56 mice; no effects on SERT protein levels; no effects on brain
5-HT levels or turnover |
| |
Anisomycin-treated
CHO cell line |
Decrease in anisomycin-induced 5-HT uptake |
| |
LPS treated BV2 microglia cell line |
Endogenous kinase inhibition measuring phosphorylated substrate
pMK2: IC50 = 332 nM. Inhibition of IL-1β overproduction:
IC50 = 936 nM |
| |
BV2
microglia cell line |
No effect on cell proliferation,
migration, or phagocytosis |
| |
APPNlh/Nlh/PS1P264L/P264L KI |
Cortex IL-1β and TNFα levels decreased in mice
showing improved performance in RAWM |
| |
APP/PS1 transgenic |
No effect on Aβ plaque
burden |
| |
APPNlh/Nlh/PS1P264L/P264L KI |
No effect on Aβ
plaque levels or volume; no effect on
levels of PBS-soluble or formic acid-soluble Aβ40 or Aβ42 |
| |
p38αMAPKT106M KI |
Cortex IL-1β and TNFα levels did not change with
MW150 treatment of drug resistant mice |
