GMI-1271 is designed to block E-selectin
, an adhesion molecule on cells in the bone marrow, from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment.
Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin
The ED biomarkers include: intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), P- and E-selectin
, vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) .
Blood sampling for plasma thiobarbituric acid-reactive substances (TBARS), vitamin C, soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin
was done on enrolment and thereafter daily until vasoconstrictor cessation and on the 7th day following cessation of vasoconstrictors.
Two ml were collected on trisodium citrate to measure prothrombin time (PT) using Thromborel S reagent (Behring werke AG) and serum endothelial markers including: TM, vWF, and E-selectin
using enzyme linked immunosorbent assay (ELISA) technique.
Total protein expression of CAMs such as E-selectin
, ICAM-1, VCAM-1 and PECAM-1 as well as phosphorylation of LvB-a were determined using western blot.
These in vitro investigations were followed by a comparative ex vivo analysis of both groups of sera with respect to the level of eight arbitrarily selected mediators of vascular inflammation (ICAM-1, VCAM-1, E-selectin
, P-selectin, uPA, PAI-1, ET-1, and TFPI) and by studies in which a concentration of these molecules in the sera was correlated with the calendar age of the serum donors.
GlycoMimetics, a United States-based biotechnology company, has commenced dosing in a Phase I/II clinical trial of its new and proprietary E-selectin
antagonist, GMI-1271, it was reported on Wednesday.
reported that E-selectin
levels were higher in an active BD group compared to controls and inactive BD (16).
Circulating inflammatory biomarkers such as CRP, IL-6, TNF-[alpha], monocyte chemotactic protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin
have been associated with a variety of metabolic disorders and associated outcomes (Goldberg 2009).
Cell adhesion molecules (CAMs)--intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin
are endothelial stress markers involved in the early atherosclerotic processes [1, 2].
P- and E-selectin
, which occur on inflamed endothelium, and their ligand, P-selectin glycoprotein ligand 1, are critical for the migration of Th1 cells to inflamed skin and peritoneum.