Table 1.
Cell adhesion molecules (CAMs) P-, E-, and L-selectin, VCAM-1, ICAM-1 and their implications in human diseases; natural ligands, and low Mw inhibitors/monoclonal antibody drug candidates.
| CAM | P-selectin | E-selectin | L-selectin | VCAM-1 | ICAM-1 |
|---|---|---|---|---|---|
| Implication in human diseases | CVS diseases, sickle cell disease (vaso-occlusive crisis), different types of cancer | CVS disease, rheumatoid arthritis, COPD and asthma, psoriasis, vaso-occlusive crisis in SCD, cancer | Sepsis, multiple organ failure | CVS disease, rheumatoid arthritis, asthma, transplant rejection, and cancer | Atherosclerosis and other CVS diseases, Breast cancer |
| Natural ligands | PSGL-1 sulfated polysaccharides (heparin) |
Structures with sLeX and sLeA ESL-1 PSGL-1 CD44 Enforced hematopoietic cell E- and L-selectin ligand (HCELL) |
PSGL-1 sulfated polysaccharides E-selectin Enforced hematopoietic cell E- and L-selectin ligand (HCELL) |
VLA-4 (integrin α4β1) MAC1 |
Lymphocyte function-associated antigen 1 (LFA1, or αLβ2 integrin) |
| Small molecule inhibitor | Bimosiamose (pan-selectin inhibitor) Sevuparin-failed in CTs for Sickle Cell disease | Cylexin (CY-1053) Rivipansel (GMI-1070) Uproleselan (s.c. version- GMI-1687) Efomycine M-failed in CTs Bimosiamose (pan-selectin inhibitor) |
Sevuparin-failed in CTs for SCD Bimosiamose (pan-selectin inhibitor) | / | / |
| Monoclonal antibodies and recombinant proteins | Crizanlizumab-approved (FDA Nov 2019) for VOC in SCD Inclacumab-in CTs for SCD diseases, after failing in CTs for CVS diseases YSPSL (rPSGL-Ig) -renal allograft-failed in clinical trials | / | Aselizumab-failed in CTs for severely injured patients | / | Enlimomab-failed in CTs, acute stroke, kidney allograft and multiple myeloma |
CTs, clinical trials; COPD, chronic obstructive pulmonary disease; CVS, cardiovascular disease; SCD, sickle cell disease; VOC, vaso-occlusive crisis.