Benevolent Platform Precision Medicine
PDE10 inhibition: potential to normalise dysregulated
mechanisms in IBD
Th1
IFNY
Dendritic Cell
TNF-KB-
IL-12
IL-6
Macrophage
IL-18
M1
M2
IL-1ẞ
IL-23
TNF
PGE2
TNFOX
IL-2
ILC3
↑IL-17A
IL-22
Th17
↑ IL-17A
IL-17F
IL-21
IL-22
IL-23
• Reduced inflammatory cytokine release
from intestinal epithelia via ↓ NFkb (1)
• Reduced tissue-resident macrophage
activation
Reduced intestinal inflammation
Source: (1) doi:10.1371/journal.pone.0079180: (2) doi:10.1371/journal.pone.0016139; (3)
doi:10.3109/00365521.2015.1038849
Na Nutrients
PDE10 inhibition
↑ CGMP ↑ CAMP
fluid
claudins
PAMR
ZO-1
occludin
MLCK
MLCK
Nutrients
TNF
• Improved TJ assembly via
PKG/PKA-mediated pMLC (2)
• Improved fluid/mucus homeostasis.
via PKG phosphorylation of
intestinal CFTR (3)
Improved barrier integrity
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