| DC60795 |
Boscalid
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Boscalid is a broad-spectrum fungicide widely used in agriculture to protect crops from fungal diseases. Its bioactivity stems from its ability to inhibit fungal respiration by targeting succinate dehydrogenase (Complex II) in the mitochondrial electron transport chain. By binding to this enzyme, Boscalid blocks electron transfer, disrupting ATP synthesis and energy production in fungal cells, ultimately leading to their death. This mechanism makes Boscalid highly effective against a wide range of fungal pathogens, including Botrytis, Alternaria, Sclerotinia, and powdery mildew species. |
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| DC67295 |
Lipid MK16
Featured
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MK16 is a novel blood-brain barrier (BBB)-crossing lipid nanoparticle (BLNP) platform developed for efficient mRNA delivery to the central nervous system (CNS). Designed through structure-guided optimization, MK16 lipids integrate a γ-secretase inhibitor-derived BBB-penetrating module (MK-0752) with ionizable amino lipids, enabling systemic mRNA transport into the brain.MK16 was selected from a library of 72 BBB-crossing lipids synthesized by conjugating small-molecule BBB transporters (e.g., L-DOPA, D-serine, MK-0752) with lipid tails. Structural refinements, including acetal-functionalized alkyl chains and optimized lipid-to-mRNA ratios (12.5:1 w/w), enhanced brain delivery efficiency. MK16 BLNPs exhibit a particle size of ~137 nm, 85% mRNA encapsulation, and a pKa of 6.7–6.9, facilitating endosomal escape.MK16 BLNPs cross the BBB via caveolae- and γ-secretase-mediated transcytosis, as validated by inhibitor studies. In mice, intravenous MK16 BLNPs delivered mRNA broadly to neurons (7.4% GFP+), astrocytes (9.7% GFP+), and brain endothelial cells (9.2% GFP+), outperforming FDA-approved LNPs (MC3, SM-102) by 6–8-fold in brain luminescence. Functional studies in Ai14 mice demonstrated Cre mRNA-mediated tdTomato activation across the hippocampus, thalamus, and cortex, with triple dosing doubling transfection efficiency.Cocaine Addiction: MK16-delivered ΔFosb mRNA enhanced cocaine-conditioned place preference in mice, mimicking addiction-related neural plasticity.
Glioblastoma (GBM): Systemic MK16-Pten mRNA inhibited orthotopic U-118MG tumor growth, achieving 70% survival at 120 days vs. controls.
Human Translation: Ex vivo human brain slices showed ΔFOSB expression in neurons (4.0%) and astrocytes (6.5%), confirming clinical potential.MK16 BLNPs exhibited minimal toxicity in multi-dose regimens, with normal blood biomarkers, cytokine levels, and histopathology. Unlike MK-0752, MK16 did NOT alter NOTCH pathway genes, mitigating off-target risks. |
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| DC60796 |
HIFN
Featured
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HIFN (2-fluoro-N-(2-(5-hydroxy-1H-indol-3-yl)ethyl)nicotinamide) is a synthetic small-molecule agonist of the tropomyosin-related kinase B (TrkB) receptor, designed to mimic brain-derived neurotrophic factor (BDNF) signaling. Structurally, HIFN replaces the six-membered lactam ring of its parent compound HIOC with a fluoropyridine moiety, rendering it achiral and configurationally stable. This modification enhances binding affinity and pharmacokinetic properties.
HIFN activates TrkB by inducing receptor dimerization and phosphorylation, triggering downstream survival pathways (PI3K/Akt, MAPK/Erk). In vitro, HIFN outperforms HIOC in TrkB activation (10 nM concentration) in primary neurons and NIH-3T3-TrkB cells. In vivo, systemic administration of HIFN (30–40 mg/kg) mitigates blast-induced retinal ganglion cell (RGC) degeneration and preserves visual function (contrast sensitivity, acuity) in mice for up to 8 weeks post-injury. Its effects are TrkB-dependent, as co-treatment with the TrkB antagonist ANA-12 abolishes neuroprotection.
HIFN exhibits a critical therapeutic window of ≤3 hours post-injury and dose-dependent efficacy, with no toxicity observed at 600 mg/kg (acute) or 40 mg/kg/day (40-day chronic). Safety assessments reveal no histopathological or biochemical abnormalities in vital organs.
By combining potent TrkB activation, blood-retina barrier penetration, and a robust safety profile, HIFN emerges as a promising therapeutic candidate for traumatic optic neuropathy and broader CNS disorders involving TrkB dysregulation. |
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| DC67296 |
Galnac GLS-15
Featured
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GLS-15 is a novel GalNAc-derived small molecule structure designed for siRNA delivery. |
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| DC67297 |
SM6.1 (αvβ6 ligand)
Featured
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SM-6.1 is a small molecule delivery vehicle developed by Arrowhead, targeting αvβ6, which selectively delivers therapeutic siRNA to lung epithelial cells and mediates durable gene silencing post-inhalation. |
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