ML324 is the first potent and cell permeable JMJD2E inhibitor with IC50 value of 920nM. In contrast to previously reported inhibitors of the JMJD proteins, ML324 displays excellent cell permeability. It demonstrated potent anti-viral activity against both herpes simplex virus (HSV) and human cytomegalovirus (hCMV) infection via inhibition viral IE gene expression at 50μM. ML324 suppressed the formation of HSV plaques, even at high MOI, and blocked HSV-1 reactivation in a mouse ganglia explant model of latently infected mice[4].
1-hour pretreatment followed by 24 hours Aa-LPS stimulation
To investigate the mechanism of KDM4B inhibition-induced immunosuppression. Results showed ML324 pretreatment significantly increased H3K4me levels, reversing the Aa-LPS-induced decrease in H3K4me.
Epigenetics. 2018;13(5):557-572.
Bone marrow-derived osteoclast progenitors
10 µM
1-hour pretreatment followed by 72 hours Aa-LPS or RANK-L stimulation
To evaluate the effect of ML324 on Aa-LPS or RANK-L-induced osteoclastogenesis. Results showed ML324 pretreatment significantly reduced osteoclast formation.
Epigenetics. 2018;13(5):557-572.
Primary murine macrophages
50 µM
1-hour pretreatment followed by 8 and 24 hours Aa-LPS stimulation
To evaluate the effect of ML324 on Aa-LPS-induced inflammatory cytokine release. Results showed ML324 significantly reduced IL-6 and TNF-α transcription and translation.
ML324 also showed inhibitory activity against early-stage gametocytes, though slightly less potent than against late-stage gametocytes
Nat Commun. 2021 Jan 11;12(1):269.
Plasmodium falciparum stage IV/V gametocytes
0.077 µM
48 hours
ML324 significantly inhibited the viability of stage IV/V gametocytes by preventing histone demethylation, leading to aberrant gene expression and death in gametocytes
ML324 exhibited lower inhibitory activity against asexual blood stage parasites, indicating selectivity towards gametocytes
Nat Commun. 2021 Jan 11;12(1):269.
Human MIBC organoids
5-40 µM
ML324 inhibited human MIBC organoids growth in a dose-dependent manner with an estimated IC50 of 10 μM
Redox Biol. 2024 Nov;77:103407.
ML324 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Inflammation model
Intravenous injection
0.2 mg/kg
Single injection, lasting 24 hours
To investigate the blocking effect of ML324 on TNF-α-mediated neutrophil adhesion, results showed ML324 could block TNF-α-mediated neutrophil adhesion.
Sci Rep. 2017 Mar 22;7:45005
Koi
CyHV-3 infection model
Immersion bath
20 µM
Daily for 3–4 h, within the first 5 days post-infection
Significantly reduced CyHV-3 replication and mortality
Viruses. 2023 Jan 5;15(1):163.
Nude mice
Orthotopic bladder cancer model
Intraperitoneal injection
25 mg/kg
Once daily for 9 days
ML324 significantly inhibited bladder tumor growth, as evidenced by fluorescence intensity monitoring
Redox Biol. 2024 Nov;77:103407.
Mice
Depression model
Intraperitoneal injection
30 mg/kg
Once daily for 5 consecutive days
ML324 treatment led to increased immobility time in the forced swim test, indicating depression-like behavior, and an increase in the transcriptionally repressive histone methylation mark H3K9me2 in NAc.
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