1. Immunology/Inflammation Cytoskeleton
  2. Toll-like Receptor (TLR) Cdc42-binding kinase Galectin
  3. 4A-MPLA ammonium

4A-MPLA ammonium is an orally active TLR4 agonist. 4A-MPLA ammonium induces TLR4 endocytosis dependent on Cdc42 and galectin-3, triggering TRIF-mediated signaling and sustained IFN-β production. 4A-MPLA ammonium promotes lipid droplet formation, upregulates interferon-stimulated genes and type I IFN signaling genes, downregulates lysosome/phagosome function genes, and modulates tolerogenic dendritic cell function. 4A-MPLA ammonium can be used for the research of colitis.

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4A-MPLA ammonium

4A-MPLA ammonium Chemical Structure

CAS No. : 2260669-09-6

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Description

4A-MPLA ammonium is an orally active TLR4 agonist. 4A-MPLA ammonium induces TLR4 endocytosis dependent on Cdc42 and galectin-3, triggering TRIF-mediated signaling and sustained IFN-β production. 4A-MPLA ammonium promotes lipid droplet formation, upregulates interferon-stimulated genes and type I IFN signaling genes, downregulates lysosome/phagosome function genes, and modulates tolerogenic dendritic cell function. 4A-MPLA ammonium can be used for the research of colitis[1][2][3].

IC50 & Target[1]

TLR4

 

Galectin-3

 

In Vitro

4A-MPLA (1.0 μg/mL; 24 h) ammonium induces a distinct cytokine profile in mouse bone-marrow-derived dendritic cells, with lower overall cytokine induction than 6A-DPLA but enhanced IFN-β production in MyD88-deficient mBMDCs[1].
4A-MPLA (10-1000 nM) ammonium binds to the human TLR4-MD2 complex with high affinity, comparable to 6A-DPLA and significantly stronger than 3A-MPLA (HY-N16231) and 5A-MPLA[1].
4A-MPLA ammonium drives a distinct transcriptomic signature in mouse bone-marrow-derived dendritic cells, strongly upregulating type I IFN and interferon-stimulated gene pathways[1].
4A-MPLA (3-48 h post-treatment) ammonium induces a sustained Ifnb mRNA response in mouse bone-marrow-derived dendritic cells, with elevated expression remaining through 36 h post-treatment[1].
4A-MPLA (15-90 min post-treatment) ammonium promotes robust TLR4 endocytosis in mouse bone-marrow-derived dendritic cells, inducing a ~30% loss of monomeric surface TLR4 by 30 min post-treatment[1].
4A-MPLA (3-24 h post-treatment) ammonium induces sustained intracellular lipid droplet formation in mouse bone-marrow-derived dendritic cells; this formation is dependent on TLR4 and TRIF signaling and persists up to 24 h post-treatment[1].
4A-MPLA ammonium-induced IFN-β production and TLR4 endocytosis in mouse bone-marrow-derived dendritic cells are dependent on Cdc42 and galectin-3 activity, as shown by dose-dependent inhibition with CASIN (HY-12874) (5-1000 nM) and anti-mGal-3 mAb (0.5-10 μg/mL)[1].
4A-MPLA ammonium preferentially engages endosomal TLR4 in mouse bone marrow-derived dendritic cells, signals through TRIF, and induces a sustained IFNβ response[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

4A-MPLA (20 μg/day; p.o.; daily; 4 days) ammonium pre-treatment potently protects against DSS (HY-116282)-induced colitis, reducing colitogenic IL-17A+ and IFN-γ+ CD4+ T cell populations in the colon[1].
4A-MPLA (100 μg/mouse; p.o.; single dose) ammonium induces a sustained IFN-β response in colonic pDCs, with elevated production persisting for at least 18 hours in naive B6 SPF IFNβ1-EYFP reporter mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: B6 SPF WT C57BL/6J mice (male or female, 6-8 weeks old)[1]
Dosage: 20 μg/day; 80 μg/mouse total
Administration: p.o.; daily; 4 days
Result: Reduced weight loss relative to control.
Reduced the proportion of IL-17A+ colonic lamina propria CD4+ T cells from 11% (control) to 3%.
Reduced the proportion of IFN-γ+ colonic lamina propria CD4+ T cells from 6% (control) to 3%.
Animal Model: Naive B6 SPF IFNβ1-EYFP reporter mice (male or female, 6-8 weeks old)[1]
Dosage: 100 μg/mouse
Administration: p.o.; single dose
Result: Increased IFN-β-producing colonic pDC proportions from a baseline of 25% to 35% at 6 hours post-treatment.
Peaked at 40% at 12 hours post-treatment.
Remained elevated at 38% at 18 hours post-treatment.
Molecular Weight

1326.76

Formula

C68H132N3O19P

CAS No.
SMILES

O[C@@H]([C@@H]([C@H]([C@H](O1)O)NC(C[C@@H](CCCCCCCCCCC)O)=O)OC(C[C@H](O)CCCCCCCCCCC)=O)[C@H]1CO[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)OP(O)(O)=O)O)NC(C[C@@H](CCCCCCCCCCC)OC(CCCCCCCCCCCCC)=O)=O.N

Structure Classification
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Room temperature in continental US; may vary elsewhere.

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Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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4A-MPLA ammonium
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HY-N16021
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