BEIJING, July 8, 2024
/PRNewswire/ -- DP Technology, an "AI for Science" paradigm-driven
company, today announced the nomination of DPT0416, a novel CNS
penetrable small molecule targeting Lp-PLA2, as a preclinical
candidate for the treatment of Alzheimer's disease (AD).
AD is the most frequent cause of dementia (60%~70%), affecting
approximately 57 million people worldwide. Neurovascular
dysfunction is an early and predominant event in AD development,
independent of classic amyloid pathology. Lp-PLA2 is a
phospholipase secreted primarily by inflammatory cells, including
peripheral macrophages and CNS microglia. It hydrolyzes oxidized
phospholipids typically on low-density lipoprotein (LDL), producing
lysophosphatidylcholine (lysoPC) and other potent proinflammatory
factors. LysoPC is a key inflammatory mediator on vascular
endothelial cells, causing vascular pathology including vessel
leakage and BBB damage. The inhibition of Lp-PLA2 by Rilapladib
significantly slowed down AD progression and repaired BBB damage
in a Phase IIa trial.
DPT0416 is a novel CNS-penetrable Lp-PLA2 inhibitor,
exhibiting higher potency, better ADME and physicochemical
properties than Rilapladib. In animal models, DPT0416 showed
improvement in BBB integrity and a reduction in brain inflammation.
The IND-enabling studies are ongoing.
"Alzheimer's disease imposes increasing burdens on the world.
Approvals of three anti-amyloid β (Aβ) antibodies mark a pivotal
moment in the fight against AD, but the modest clinical efficacy
and side effects highlight the complexity of AD and call for more
novel interventions with better efficacy. The future treatment of
AD should address multiple aspects of the disease, including
anti-oxidants, anti-inflammation, and enhancing brain resilience,
among others," said Xiaomin
Zhang, Head of Drug Discovery at DP Technology.
"Targeting Lp-PLA2 is a novel therapy that addresses multiple
factors beyond amyloid. Given rilapladib's positive clinical
results, the better molecule DPT0416 is expected to bring more
benefits to AD and dementia patients."
"DP Technology is revolutionizing the AI for Science landscape
by integrating 'AI + Simulation + Experiments' into our processes
to address significant medical needs," said Weijie Sun, Founder and CEO of DP
Technology. "The successful identification of DPT0416
highlights the power of our RiDYMO® platform, particularly the
contributions of the Uni-FEP and Uni-QSAR modules in enhancing
molecular interactions, drug-like characteristics, and BBB
penetration. These real-world applications of our cutting-edge
algorithms signify an important progression towards our envisioned
future. We look forward to forging partnerships with trusted
collaborators to advance this initiative to the next pivotal
stage."
The RiDYMO® drug design platform integrates various AI and
physical algorithms, dedicated to the development of drugs for
"undruggable" targets and "best-in-class" molecules. As one of its
core algorithms, Reinforced Dynamics (RiD) has a significant
advantage in the sampling efficiency of molecular dynamics
simulation. By fully leveraging the high-dimensional representation
capabilities of neural networks, RiD can efficiently capture
dynamic conformational changes in complicated biomolecular
systems.
The RiDYMO® platform is dedicated to studying the dynamics of
biological systems and revealing cryptic binding sites,
encompassing a range of challenging systems including
protein-protein interactions (PPIs), intrinsically disordered
proteins (IDPs), membrane proteins, RNA, and others. Its
effectiveness has been confirmed through validation on challenging
targets, including the c-Myc protein, c-Myc RNA, GPX4 protein,
Kv1.3 protein, and others.
About DP Technology
DP Technology, an "AI for Science" new paradigm-driven company,
dedicated to applying Artificial Intelligence and Molecular
Simulation algorithms to solve important scientific problems by
combining advanced computational methods.
Relying on DP Technology's Dynamics-based drug design platform,
RiDYMO®, we have set up a world-leading hit discovery platform. The
team has established external collaborations and built up strong
internal pipeline, focusing on three areas of CNS, oncology and
autoimmune diseases.
For collaboration and further information,please contact Dr.
Xiaomin Zhang
(zhangxm@dp.tech).
References:
[1] Alzheimers. Dement. 17(Suppl 10),
e051496 (2021).
[2] Nat. Med. 25, 270-276 (2019).
[3] Med. Res. Rev. 40, 79-134 (2020).
[4] Alzheimers. Dement. 1, 131-140 (2015).
[5] Diab. Vasc. Dis. Res. 14, 200-213 (2017).
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SOURCE DP Technology