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Chemical Structure| 1991986-30-1 Chemical Structure| 1991986-30-1

Structure of ML364
CAS No.: 1991986-30-1

Chemical Structure| 1991986-30-1

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CAS No.: 1991986-30-1

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ML364 is a USP2 inhibitor with IC50=1.1 μM, which directly binds to USP2 (Kd=5.2 μM) and promotes the degradation of cyclin D1, leading to cell cycle arrest.

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Product Details of ML364

CAS No. :1991986-30-1
Formula : C24H18F3N3O3S2
M.W : 517.54
SMILES Code : O=C(NC1=NC(C2=CC=CC=C2)=CS1)C3=CC=C(C(F)(F)F)C=C3NS(=O)(C4=CC=C(C)C=C4)=O
MDL No. :MFCD30718174
InChI Key :QZUGMNXETPARLI-UHFFFAOYSA-N
Pubchem ID :70789348

Safety of ML364

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
SH-SY5Y cells 10 μM 2 hours To evaluate the effect of ML364 on AMPK phosphorylation in neural cells. ML364 treatment increased AMPK phosphorylation, decreased intracellular ATP content, and disrupted the activities of mitochondrial respiratory chain complexes I, II, and IV. PMC9186793
Caki-1 cells 2 μM 24 hours ML364 induces survivin downregulation and enhances TRAIL-mediated apoptosis in cancer cells. PMC10454696
Pseudomonas aeruginosa PAO1 64–256 μg/ml 24 hours ML364 significantly inhibited pyocyanin production, reducing it to 46% and 34% in PAO1 and CRPA 16-2 respectively at 256 μg/ml PMC9813848
Mino cells 10 μM 4 hours ML364 reduced cyclin D1 protein levels in a time-, dose-, and proteasome-dependent manner. PMC5114414
HCT116 cells 10 μM 4 hours ML364 reduced cyclin D1 protein levels in a time-, dose-, and proteasome-dependent manner. PMC5114414
Calu-3 4 μM 48 hours ML364 treatment significantly reduced the replication of SARS-CoV-2 WT, Beta, and Delta variants. PMC10787358
HepG2 10 μM 48 hours ML364 treatment led to a reduction in ACE2 protein abundance and inhibited SARS-CoV-2 pseudovirus entry into cells. PMC10787358
Staphylococcus aureus ATCC 29213 16–64 μg/ml 48 hours ML364 significantly inhibited staphyloxanthin production, reducing it to 59% and 52% in ATCC 29213 and MRSA 08-50 respectively at 64 μg/ml PMC9813848
Vibrio campbellii MM32 0.25–64 μg/ml 6 hours ML364 significantly inhibited DPD/AI-2 signaling response, with 0.5 μg/ml ML364 showing maximum inhibition for AI-2 stimulation PMC9813848
AU565 10 μM various time points ML364 accelerates ErbB2 turnover by inducing its ubiquitylation and enhances the pro-degradation effects of HSP90 inhibitors on ErbB2. PMC7429833
HCC1954 10 μM various time points ML364 accelerates ErbB2 turnover by inducing its ubiquitylation and enhances the pro-degradation effects of HSP90 inhibitors on ErbB2. PMC7429833
SKBR3 10 μM various time points ML364 accelerates ErbB2 turnover by inducing its ubiquitylation and enhances the pro-degradation effects of HSP90 inhibitors on ErbB2. PMC7429833
A549 cells 2 μM 24 hours ML364 induces survivin downregulation in A549 cells. PMC10454696
DU145 cells 2 μM 24 hours ML364 induces survivin downregulation in DU145 cells. PMC10454696
ACHN cells 2 μM 24 hours ML364 induces survivin downregulation in ACHN cells. PMC10454696
NHBE 10 μM 48 hours ML364 treatment inhibited SARS-CoV-2 WT infection in NHBE cells. PMC10787358

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Male C57BL/6N mice VMH cannulation model Intra-VMH injection 20 ng/head Single injection, observed for 120 minutes To investigate the effect of ML364 on blood glucose levels. ML364 injection into the VMH significantly increased blood glucose levels within 30 minutes, along with increased serum norepinephrine concentration and hepatic glycogen phosphorylase activity, indicating that USP2 suppresses glucose mobilization by modulating sympathetic nervous activity. PMC9186793
ICR mice Systemic infection model Intraperitoneal injection 3 mg/kg Administered at 0, 12, and 24 hours post-infection, monitored for 4 days ML364 significantly improved survival rates of systemically infected mice and reduced bacterial loads in organs PMC9813848
Nude mice HCC1954 xenograft model Intraperitoneal injection 5 mg/kg Daily for 3 weeks The combination of ML364 and 17-AAG significantly inhibited the growth of HCC1954 xenografts and reduced ErbB2 expression levels. PMC7429833
K18-hACE2 transgenic mice SARS-CoV-2 infection model Intraperitoneal injection 50 mg/kg Once daily for 4 days ML364 treatment significantly reduced viral loads in the lungs and ameliorated lung pathology. PMC10787358

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.66mL

1.93mL

0.97mL

19.32mL

3.86mL

1.93mL

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