ML348 | CAS#899713-86-1 | LYPLA1 inhibitor

MedKoo Cat#: 406957 | Name: ML348

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ML348, also known as CID 3238952; SID 160654487, is a reversible LYPLA1 inhibitor with an IC50 value of 210 nM. Multiple oncogenes, including HRAS and SRC, require palmitoylation for malignant transformation. Lysophospholipase 1 (LYPLA1) has been identified as a candidate protein palmitoyl thioesterase responsible for HRAS depalmitoylation in mammalian cells.

Chemical Structure

ML348

CAS#899713-86-1

Theoretical Analysis

MedKoo Cat#: 406957

Name: ML348

CAS#: 899713-86-1

Chemical Formula: C18H17ClF3N3O3

Exact Mass: 415.0911

Molecular Weight: 415.80

Elemental Analysis: C, 52.00; H, 4.12; Cl, 8.53; F, 13.71; N, 10.11; O, 11.54

Price and Availability

Size	Price	Availability
100mg	USD 650.00	2 Weeks
200mg	USD 950.00	2 Weeks
500mg	USD 1,650.00	2 Weeks
1g	USD 2,750.00	2 Weeks
2g	USD 4,250.00	2 Weeks

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Synonym

ML348; ML-348; ML 348; CID 3238952; SID 160654487.

IUPAC/Chemical Name

N-[2-chloro-5-(trifluoromethyl)phenyl]-4-(2-furanylcarbonyl)-1-piperazineacetamide

InChi Key

OXKNHBBDOIMFFQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H17ClF3N3O3/c19-13-4-3-12(18(20,21)22)10-14(13)23-16(26)11-24-5-7-25(8-6-24)17(27)15-2-1-9-28-15/h1-4,9-10H,5-8,11H2,(H,23,26)

SMILES Code

O=C(NC1=CC(C(F)(F)F)=CC=C1Cl)CN2CCN(C(C3=CC=CO3)=O)CC2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

ML348 (GNF-Pf-1127) is a selective and reversible acyl-protein thioesterase 1 (APT1)/lysophospholipase 1 (LYPLA1) inhibitor with an IC50 of 210 nM, and barely inhibits LYPLA2.

In vitro activity:

To determine whether ML348 is neurotoxic, this study first treated WT primary cortical neuron cultures for 50 hours at increasing concentrations and found no overt toxicity for concentrations up to 10 μM (fig. S6B). This study also treated cortical neurons daily for 10 days with 1 μM ML348, a concentration chosen on the basis of the ML348 IC50 for APT1 (230 nM). ML348 treatment restored the anterograde and retrograde velocities as well as the number of vesicles moving in both directions to control levels (Fig. 4, D and E). The linear flow rate was similar to that of controls, indicating that ML348 fully restored BDNF axonal flow to the synapse in HD neurons (Fig. 4F). Reference: Sci Adv. 2021 Mar 31;7(14):eabb0799. https://pubmed.ncbi.nlm.nih.gov/33789888/

In vivo activity:

This study assessed motor coordination using the horizontal ladder test. CAG140 mice showed significant deficits in this task, with a high error rate and longer average time to cross the ladder (Fig. 5C), but ML348 treatment restored their performance to the level of WT mice (Fig. 5C and movie S1). ML348 significantly improved the motor coordination of CAG140 mice (Fig. 5, C and D). Reference: Sci Adv. 2021 Mar 31;7(14):eabb0799. https://pubmed.ncbi.nlm.nih.gov/33789888/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	72.15
	DMSO	44.9	107.97
	Ethanol	15.0	36.08
	PBS (pH 7.2)	10.0	24.05

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 415.80 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

Virlogeux A, Scaramuzzino C, Lenoir S, Carpentier R, Louessard M, Genoux A, Lino P, Hinckelmann MV, Perrier AL, Humbert S, Saudou F. Increasing brain palmitoylation rescues behavior and neuropathology in Huntington disease mice. Sci Adv. 2021 Mar 31;7(14):eabb0799. doi: 10.1126/sciadv.abb0799. PMID: 33789888; PMCID: PMC8011966.

In vitro protocol:

In vivo protocol:

1: Won SJ, Davda D, Labby KJ, Hwang SY, Pricer R, Majmudar JD, Armacost KA, Rodriguez LA, Rodriguez CL, Chong FS, Torossian KA, Palakurthi J, Hur ES, Meagher JL, Brooks CL 3rd, Stuckey JA, Martin BR. Molecular Mechanism for Isoform-Selective Inhibition of Acyl Protein Thioesterases 1 and 2 (APT1 and APT2). ACS Chem Biol. 2016 Oct 31. [Epub ahead of print] PubMed PMID: 27748579. 2: Vujic I, Sanlorenzo M, Esteve-Puig R, Vujic M, Kwong A, Tsumura A, Murphy R, Moy A, Posch C, Monshi B, Rappersberger K, Ortiz-Urda S. Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitors palmostatin B, ML348 and ML349 have different effects on NRAS mutant melanoma cells. Oncotarget. 2016 Feb 9;7(6):7297-306. doi: 10.18632/oncotarget.6907. PubMed PMID: 26771141; PubMed Central PMCID: PMC4872786. 3: Hulce JJ, Joslyn C, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. An in Vivo Active Carbamate-based Dual Inhibitor of Lysophospholipase 1 (LYPLA1) and Lysophospholipase 2 (LYPLA2). 2013 Dec 9 [updated 2014 Sep 18]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK259193/ PubMed PMID: 25506974. 4: Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. Characterization of a Selective, Reversible Inhibitor of Lysophospholipase 2 (LYPLA2). 2013 Apr 8 [updated 2014 Sep 18]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK189927/ PubMed PMID: 24624468. 5: Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Cravatt BF, Hodder P, Rosen H. Characterization of a Selective, Reversible Inhibitor of Lysophospholipase 1 (LYPLA1). 2013 Apr 8 [updated 2014 Jan 13]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK189924/ PubMed PMID: 24624465.