Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages

Jonah E Zarrow, Abdul-Musawwir Alli-Oluwafuyi, Cristina M Youwakim, Kwangho Kim, Andrew N Jenkins, Isabelle C Suero, Margaret R Jones, Zahra Mashhadi, Ken Mackie, Alex G Waterson, Amanda C Doran, Gary A Sulikowski, Sean S Davies. ACS Chem Biol. 2023 Aug 18;18(8):1891-1904.

Laboratory studyOther animals

Design

Laboratory study

Subjects

Mouse and human NAPE-PLD enzyme assays and bone marrow derived macrophages from wild-type and Napepld knockout mice

Dose used in the study

Not applicable; palmitoylethanolamide was not given

Duration

Not stated in the abstract

What was measured

High-throughput screening for NAPE-PLD activators and their effect on macrophage efferocytosis (clearance of dead cells)

What the authors reported

The study found:

• A series of benzothiazole phenylsulfonyl-piperidine carboxamides increased mouse and human NAPE-PLD activity.
• Two activators, VU534 and VU533, increased efferocytosis by wild-type mouse macrophages, while efferocytosis fell in knockout cells or after enzyme inhibition.
• The authors note NAPE-PLD products such as PEA and OEA have been shown to enhance efferocytosis.

Limits of this study

A drug-discovery cell study; it cannot show effect in people or animals. PEA is background, not the tested agent. Six authors are inventors on a patent application for these activators; NIH and AHA funding.

Source

PubMed 37531659 · doi:10.1021/acschembio.3c00401

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.