PXD069894-1

PXD069894 is an original dataset announced via ProteomeXchange.

Title	Suppression of pain transmission and behavior by inhibition of peripheral diacylglycerol metabolism
Description	This submission includes MS data for the paper titled "Suppression of pain transmission and behavior by inhibition of peripheral diacylglycerol metabolism", submitted to Cell Chemical Biology. Summary: Diacylglycerol lipase (DAGL) produce 2-arachidonoylglycerol (2-AG) and other proinflammatory lipids. Inactivation of DAGLs reduces the production of 2-AG, arachidonic acid (AA) and eicosanoids and elicits antinociceptive and anti-(neuro)inflammatory effects in rodents. However, inhibitors that enter the brain can cause significant central nervous system (CNS) side effects. Using activity-based protein profiling (ABPP), we report the discovery of A1480LS, a potent, in vivo active, small molecule dual inhibitor of DAGLα/β that is functionally biased to the periphery. We demonstrate that A1480LS reduces pain in animal models of both inflammatory and neuropathic pain. Moreover, A1480LS accomplishes this by reducing 2-AG and other lipids in peripheral tissues, all without causing adverse CNS effects of seizures. Overall, we show that inhibiting DAG metabolism in the periphery elicits antinociceptive effects that can be functionally dissected from adverse central effects and provide preclinical validation for a non-narcotic strategy to treat pain. Raw files for the selectivity experiment profiling of A1480LS in THP1 cells are listed below. Search and quantification results bearing the same file stem are also provided, as well as the fasta database that was used: uniprot_HumanComplete_121105_cdhit98_plus_Reverse_wContaminants150305.fasta. - RAH-NB1-208_A_03.raw Raw files for the in vivo time course experiment in rat kidneys are listed below. A Skyline export bearing the same name is also provided, as well as the fasta database that was used: uniprot_6organism_constructs_contaminants_20190213_forPRMJOB.fasta. - NN-NB2-213_A1.raw: 0h, Vehicle - NN-NB2-213_A2.raw: 0h, Vehicle - NN-NB2-213_A3.raw: 0h, Vehicle - NN-NB2-213_A4.raw: 0h, Vehicle - NN-NB2-213_B1.raw: 1h, A1480LS - NN-NB2-213_B2.raw: 1h, A1480LS - NN-NB2-213_B3.raw: 1h, A1480LS - NN-NB2-213_B4.raw: 1h, A1480LS - NN-NB2-213_B5.raw: 4h, A1480LS - NN-NB2-213_B6.raw: 4h, A1480LS - NN-NB2-213_B7.raw: 4h, A1480LS - NN-NB2-213_B8.raw: 4h, A1480LS - NN-NB2-213_B9.raw: 8h, A1480LS - NN-NB2-213_B10.raw: 8h, A1480LS - NN-NB2-213_B11.raw: 8h, A1480LS - NN-NB2-213_B12.raw: 12h, A1480LS - NN-NB2-213_C1.raw: 12h, A1480LS - NN-NB2-213_C2.raw: 12h, A1480LS - NN-NB2-213_C3.raw: 12h, A1480LS - NN-NB2-213_C4.raw: 24h, A1480LS - NN-NB2-213_C5.raw: 24h, A1480LS - NN-NB2-213_C6.raw: 24h, A1480LS - NN-NB2-213_C7.raw: 24h, A1480LS - NN-NB2-213_C8.raw: 32h, A1480LS - NN-NB2-213_C9.raw: 32h, A1480LS - NN-NB2-213_C10.raw: 32h, A1480LS - NN-NB2-213_C11.raw: 32h, A1480LS
HostingRepository	PRIDE
AnnounceDate	2026-01-16
AnnouncementXML	Submission_2026-01-15_16:29:10.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Radu Suciu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	2x(13)C; monohydroxylated residue; dimethylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-24 20:56:13	ID requested
⏵ 1	2026-01-15 16:29:11	announced

10.1016/J.CHEMBIOL.2025.12.008;

submitter keyword: None

Jason R.
contact affiliation	Lundbeck La Jolla Research, San Diego, USA
contact email	JACP@lundbeck.com
lab head
Radu Suciu
contact affiliation	Lundbeck La Jolla Research Center
contact email	radusuciu@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069894
     1. Label: PRIDE project
     2. Name: Suppression of pain transmission and behavior by inhibition of peripheral diacylglycerol metabolism