Home Metabolism Phospholipase (e.g. PLA) inhibitor ML348 For research use only.

ML348

Synonyms: GNF-Pf-1127

ML348 (GNF-Pf-1127) is a potent and selective APT1 (Acyl protein thioesterase 1)/lysophospholipase 1 (LYPLA1) inhibitor with Ki values of 280 nM and >10 μM for APT1 and APT2, respectively.

ML348 Chemical Structure

ML348 Chemical Structure

CAS No. 899713-86-1

Purity & Quality Control

ML348 Related Products

Signaling Pathway

Phospholipase (e.g. PLA) Signaling Pathways

Phospholipase (e.g. PLA) Signaling Pathway

Biological Activity

Description ML348 (GNF-Pf-1127) is a potent and selective APT1 (Acyl protein thioesterase 1)/lysophospholipase 1 (LYPLA1) inhibitor with Ki values of 280 nM and >10 μM for APT1 and APT2, respectively.
Targets
APT1 [1]
280 nM(Ki)
In vitro
In vitro

ML348 increases brain palmitoylation and inhibits the palmitate-removing enzyme acyl-protein thioesterase 1 (APT1), restores axonal transport, synapse homeostasis, and survival signaling to wild-type levels without toxicity, also increases BDNF trafficking in human HD induced pluripotent stem cell-derived cortical neurons.[2]
Cell Research Cell lines STHdh cells, human HD patient iPSC-derived cortical neurons, CAG140 neurons
Concentrations 10, 1 μM
Incubation Time 1, 4h
Method

ML348, palmostatin B, and ML349 are diluted in 100% dimethyl sulfoxide (DMSO) for primary concentration. For STHdh cells and immunofluorescence of neurons plated on coverslips, we administered acute treatment with 10 μM for 1 hour before and during the acquisition time. For the fractionation experiments, we plated cortical neurons on 10-cm dishes and we treated cells for 4 hours with 1 μM ML348 before lysis. For neurons within microchambers, 1 μM ML348 is administered within each compartment of the microfluidic device beginning on days in vitro (DIV)2 and continuing daily until DIV12, while for BDNF pHluorin analysis, compartments are treated for 4 hours with 1 μM ML348 before acquisition.
In Vivo
In vivo

In HD knock-in mice, ML348 efficiently crosses the blood-brain barrier to restore palmitoylation levels and reverse neuropathology, locomotor deficits, and anxio-depressive behaviors.[2]

Chemical Information & Solubility

Molecular Weight 415.79 Formula

C18H17ClF3N3O3
CAS No. 899713-86-1 SDF --
Smiles C1CN(CCN1CC(=O)NC2=C(C=CC(=C2)C(F)(F)F)Cl)C(=O)C3=CC=CO3
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 83 mg/mL ( (199.62 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 21 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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