ML348

Catalog No.S6564 Batch:S656401

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Technical Data

Formula

C18H17ClF3N3O3
Molecular Weight 415.79 CAS No. 899713-86-1
Solubility (25°C)* In vitro DMSO 83 mg/mL (199.62 mM)
Ethanol 10 mg/mL (24.05 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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

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]
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]

Protocol (from reference)

Cell Assay:

[2]
  • 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.

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.