Selectin
Selectins are vascular adhesion molecules that mediate physiological responses such as inflammation, immunity and hemostasis. The selectins are a family of three C-type lectins expressed by bone-marrow-derived cells and endothelial cells. These vascular cell adhesion molecules are identified as L-selectin expressed on leukocytes, E-selectin expressed on endothelial cells ad P-selectin expressed on platelet and endothelial cells. All three selectins have a similar structure consisting of an amino-terminal lectin domain, one EGF-like domain, several consensus repeats, a single transmembrane domains and a carboxy-terminal cytoplasmic domain. The main physiological function of all selectins is to mediate leukocyte recruitment to sites of inflammation or to lymphoid tissues.
P-selectin is found in secretory granules of platelets (α-granules) and endothelial cells (Weibel-Palade bodies) and upon activation is present on the surface of platelets and endothelial cells. E-selectin expression on activated endothelial cells requires de novo transcription, thus occurs several hours after stimulation and persists for a longer time period as observed in chronic inflammation. L-selectin is expressed by all myeloid-derived cells, naïve T cells, and some memory T cells. Selectins promote tumor cell-endothelial interaction and the recruitment of leukocytes. a: Platelet binding to tumor cells and to the endothelium promote tumor cell adhesion. The intracellular signaling in leukocytes is initiated through selectin-binding to PSGL-1 on leukocytes resulting in 1: activation of MAPK and src kinase pathways; 2: activation of integrins; 3: activation of NF-κB pathways and secretion of cytokines (e.g. CCL2, IL-8 or TNF-α; 4: shedding of cell surface L-selectin.
References
1.Lubor Borsig. Glycobiology. 2018 Aug 31; 28(9): 648–655.
P-selectin is found in secretory granules of platelets (α-granules) and endothelial cells (Weibel-Palade bodies) and upon activation is present on the surface of platelets and endothelial cells. E-selectin expression on activated endothelial cells requires de novo transcription, thus occurs several hours after stimulation and persists for a longer time period as observed in chronic inflammation. L-selectin is expressed by all myeloid-derived cells, naïve T cells, and some memory T cells. Selectins promote tumor cell-endothelial interaction and the recruitment of leukocytes. a: Platelet binding to tumor cells and to the endothelium promote tumor cell adhesion. The intracellular signaling in leukocytes is initiated through selectin-binding to PSGL-1 on leukocytes resulting in 1: activation of MAPK and src kinase pathways; 2: activation of integrins; 3: activation of NF-κB pathways and secretion of cytokines (e.g. CCL2, IL-8 or TNF-α; 4: shedding of cell surface L-selectin.
References
1.Lubor Borsig. Glycobiology. 2018 Aug 31; 28(9): 648–655.
Cytoskeleton/Cell Adhesion Molecules
Selectin
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GMI-1070
catalog no : M16645
cas no: 927881-99-0
GMI-1070 (Rivipansel, PF-06460031)?is a novel small molecule glycomimetic pan-Selectin antagonist with IC50 of 4.3 uM, 423 uM and 337 uM for E-selectin, P-selectin and L-selectin, respectively. -
HMCEF
catalog no : M13124
cas no: 2002363-68-8
A novel P-selectin inhibitor that directly binds to P-selectin. -
GMI-1271
catalog no : M13000
cas no: 1914993-95-5
A novel specific glycomimetic E-Selectin antagonist with Kd of 0.46 uM, IC50 of 1.75 uM. -
Rivipansel sodium
catalog no : M10649
cas no: 1189037-60-2
Rivipansel sodium (GMI-1070, PF-06460031)?is a novel small molecule glycomimetic pan-Selectin antagonist with IC50 of 4.3 uM, 423 uM and 337 uM for E-selectin, P-selectin and L-selectin, respectively. -
PSI-421
catalog no : M10287
cas no: 1067186-56-4
A potent, orally bioavailable P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury.