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Chemical Structure| 19992-50-8 Chemical Structure| 19992-50-8

Structure of ML329
CAS No.: 19992-50-8

Chemical Structure| 19992-50-8

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ML329 is a small molecule inhibitor of MITF which inhibits TRPM-1 promoter activity with an IC50 of 1.2 μM.

Synonyms: ML329

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Sundaramurthi, Husvinee ; Garcia-Mulero, Sandra ; Tonelotto, Valentina ; Slater, Kayleigh ; Marcone, Simone ; Piulats, Josep M. , et al.

Abstract: Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying mol. mechanisms. A significant (p = 0.0001) dose-dependent reduction in surviving clones of the primary ocular UM cells, Mel270, was observed upon treatment with increasing doses of ACY-1215. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo attenuation of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0001) following 24 h of treatment, and significant apoptosis was triggered in a time- and dose-dependent manner (p < 0.0001). Addnl., ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome profiling, the attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacol. inhibition of MITF signaling with ML329 significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and reduced OMM2.5 cells in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of OMM2.5 MUM cells.

Keywords: metastatic uveal melanoma ; HDAC inhibitor ; ACY-1215 ; MITF ; p-ERK ; ML329 ; zebrafish xenografts

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Husvinee Sundaramurthi ; Sandra García-Mulero ; Kayleigh Slater ; Simone Marcone ; Josep M.Piulats ; R. William Watson , et al.

Abstract: Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase 6 inhibitor (HDAC6i), to attenuate MUM cell growth in vitro and in vivo, and elucidate the underlying molecular mechanisms. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo regression of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry analysis revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0006) following 24 hours of treatment and significant apoptosis was triggered in a time- and dose-dependent manner (p = <0.0001). Additionally, ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome-profiling, attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacological inhibition of MITF signaling with ML329, significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of MUM cells and are potential therapeutic options for MUM. Simple Summary Uveal melanoma (UM) is the most common adult eye cancer. UM originates in the iris, ciliary body, or choroid (collectively known as the uvea), in the middle layer of the eye. This first or primary UM is treated by targeting the cancer cells using ocular radiation implants or by surgical removal of the eye. However, when UM spreads to the liver and other parts of the body, patients have a poor survival prognosis. Unfortunately, there are no effective treatment options for UM that has spread. Our aim is to help identify effective treatments for UM cancer that has spread. In our study, we identified that the drug ACY-1215 prevents the growth of UM cells from the liver. Our study has found a promising treatment approach for advanced UM.

Keywords: Metastatic uveal melanoma ; HDAC6 inhibitor ; ACY-1215 ; MITF ; p-ERK ; ML329 ; Zebrafish xenografts

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Product Details of ML329

CAS No. :19992-50-8
Formula : C16H12N2O4S
M.W : 328.34
SMILES Code : O=S(C1=CC=C(NC(C2=O)=CC(C3=C2C=CC=C3)=O)C=C1)(N)=O
Synonyms :
ML329
MDL No. :MFCD30579194
InChI Key :CSYFFQVEQXEIAB-UHFFFAOYSA-N
Pubchem ID :12387471

Safety of ML329

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

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.05mL

0.61mL

0.30mL

15.23mL

3.05mL

1.52mL

30.46mL

6.09mL

3.05mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

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