transcellular

Salcaprozate sodium (SNAC), an oral absorption promoter, enhances passive transcellular permeation through small intestinal epithelia, making it a potent delivery agent for oral heparin and insulin by increasing lipophilicity via non-covalent macromolecule complexation.

VSWRAPTA is a promoter of neuronal branching via transcellular activation of the focal adhesion kinase (FAK) and the ERK1/2 signaling pathway in vitro.

Lipoxin A4 methyl ester (LXA4 methyl ester) is a more lipid soluble, prodrug formulation of the transcellular metabolite LXA4. LXA4 is a trihydroxy fatty acid containing a conjugated tetraene, produced by the metabolism of 15-HETE or 15-HpETE with human leukocytes.[1] LXA4 is equipotent to leukotriene B4 (LTB4) in inducing superoxide generation in human neutrophils at 0.1 μM.[2] LXA4 is associated with several other biological functions including leukocyte activation, chemotaxis effects, natural killer cell inhibition, and monocyte migration and adhesion.[2],[3],[4]

Leukotriene C4 (LTC4) is the parent cysteinyl-leukotriene produced by the LTC4 synthase-catalyzed conjugation of glutathione to LTA4. LTC4 is produced by neutrophils, macrophages, and mast cells, and by transcellular metabolism in platelets. It is one of the constituents of slow-reacting substance of anaphylaxis (SRS-A) and exhibits potent smooth muscle contracting activity. LTC4-induced bronchoconstriction and enhanced vascular permeability contribute to the pathogenesis of asthma and acute allergic hypersensitivity. The concentration of LTC4 required to produce marked contractions of lung parenchymal strips and isolated tracheal rings is about 1 nM. LTC4 methyl ester is a more lipid soluble form of LTC4. The biological activity of LTC4 methyl ester has not been reported.

N-methyl Leukotriene C4 (250 μg/ml solution in ethanol) is a metabolically stable synthetic analogue of Leukotriene C4 that resists enzymatic conversion into LTD4 and LTE4. N-methyl Leukotriene C4 is a valuable experimental tool for investigations involving leukotriene signaling, inflammatory mediator biology, eicosanoid metabolism, and receptor-associated inflammatory pathways.

Resolvin E4 (RvE4) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acid by 15-lipoxygenase (15-LO)via15(S)-HpEPE and 15S-hydroxy, 5S-HpEPE intermediatesin vitroand by isolated human M2 macrophages or polymorphonuclear (PMN) neutrophils under normoxic or hypoxic conditions. RvE4 synthesis is enhanced in M2 macrophage and neutrophil co-cultures, indicating transcellular biosynthesis by a potential 15-LO and 5-LO mechanism. It has been found in mouse inflammatory exudates. RvE4 (10 nM) increases efferocytosis of apoptotic neutrophils or senescent red blood cells (sRBCs) by human M2 macrophages under hypoxic conditionsin vitro. Intraperitoneal administration of RvE4 (100 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of hemorrhagic peritonitis induced by zymosan A and thrombin. It also increases inflammatory exudate macrophage infiltration and efferocytosis of apoptotic neutrophils and/or RBCs in the same model. 1.Norris, P.C., Libreros, S., and Serhan, C.N.Resolution metabolomes activated by hypoxic environmentSci. Adv.5(10)eaax4895(2019)

Lipoxin B4 (LXB4) methyl ester is a lipid-soluble prodrug form of the transcellular metabolite LXB4, which is a positional isomer of LXA4 produced by the metabolism of 15-HETE or 15-HpETE by human leukocytes. At 100 nM, LXB4 inhibits polymorphonuclear leukocyte (PMN) migration stimulated by leukotriene B4 and inhibits LTB4-induced adhesion of PMNs with an IC50 of 0.3 nM.

PBT434 methanesulfonate is an orally active, potent α-synuclein aggregation inhibitor with the ability to cross the blood-brain barrier. Acting as an iron chelator, it modulates transcellular iron trafficking, inhibits iron-mediated redox activity, and prevents iron-mediated aggregation of α-synuclein. PBT434 methanesulfonate also safeguards against the loss of substantia nigra pars compacta neurons (SNpc), showing promise for Parkinson's disease (PD) research.

pTH-Related Protein (1-40) (human, mouse, rat) enhances calcium absorption in rat intestinal cells by activating the PTHR1 receptor and the PKCα/β signaling pathways. This compound also increases the expression of the parathyroid hormone 1 receptor (PTHR1) and four key proteins involved in transcellular calcium transport: potential vanillin member 6 (TRPV6), calcium-binding protein-D9K (CaBP-D9k), sodium-calcium exchanger 1 (NCX1), and plasma membrane calcium ATPase 1 (PMCA1) [1].

Oleoyl 3-carbacyclic Phosphatidic Acid are naturally occurring lysophosphatidic acid (LPA) analogs characterized by a five-membered ring formed between the sn-2 hydroxy group and the sn-3 phosphate moiety. Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1) contains the 18:1 fatty acid oleate at the sn-1 position of the glycerol backbone and functions as a cyclic lysophosphatidic acid analog. At a concentration of 25 μM, Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1) inhibits MM1 cell transcellular migration through mesothelial cell monolayers induced by fetal bovine serum by 90.1% and by lysophosphatidic acid by 99.9%, without affecting cell proliferation. Furthermore, Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1), at concentrations ranging from 0.1 to 1.0 μM, markedly suppresses autotaxin, a key regulator of cancer cell survival, growth, migration, invasion, and metastasis. These findings support the application of Oleoyl 3-Carbacyclic Phosphatidic Acid (3-ccPA 18:1) in studies of lysophospholipid signaling, cancer cell biology, cell migration, and autotaxin-mediated molecular mechanisms.

15(R)-HETE, a monohydroxy fatty acid, is synthesized from arachidonic acid via aspirin-acetylated COX-2, leading to the formation of specialized pro-resolving mediators 15(R)-lipoxin A4 and B4 through a transcellular mechanism involving 5-lipoxygenase (5-LO). Additionally, this compound is produced by the cytochrome P450 (CYP) isoform CYP2C9 and can be generated from arachidonic acid by COX-1 in human mast cells, where it accumulates due to its resistance to conversion into 15-KETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). As an agonist of PPARβ/δ, 15(R)-HETE induces the expression of a target gene in NIH3T3 cells, demonstrating its biological significance.