. Author manuscript; available in PMC: 2019 Aug 1.

Published in final edited form as: Nat Rev Drug Discov. 2019 Feb;18(2):139–158. doi: 10.1038/s41573-018-0003-2

Table 5 |.

Anti-adhesive agents

Therapeutic agent	Properties	Comments
Rivipansel	Small molecule pan-selectin inhibitor with strongest activity against E selectin	Successful phase 2 (NCT01119833)¹⁴⁹; currently in phase 3 trial (NCT02187003)
Crizanlizumab	Humanized monoclonal antibody that inhibits P selectin.	Successful phase 2 study showing safety and efficacy (NCT01895361)¹⁵⁰
Sevuparin	Heparinoid that blocks P selectin and other adhesive ligands	Inhibited RBC and leukocyte adhesion to endothelial cells in vitro and in SCD mice¹⁵¹
Nonsulfated heparins	Blocks P-selectin and possibly other adhesive ligands	Blocked RBC adhesion in vitro and pretreatment of both erythrocytes and decreases ICAM-1 and sP-SEL in SCD mice¹⁵³
Anti-selectin aptamers	Blocks P selectin-mediated adhesion	Blocks adhesion in vitro and in animal studies ^277,278
αvβ3 inhibition	Blocks adhesion of RBC via ICAM-4 to endothelial cell αvβ3	Blocked RBC and WBC adhesion to endothelial cells in vitro and in animal models ^17,154,155
MAST-188 (Poloxamer 188)	Non-specific inhibition of cell adhesion	Unsuccessful in repeated phase 3 studies (NCT00004408, NCT01737814)
Beta blockers	Prevents activation of RBC adhesion receptors ICAM-4, BCAM/Lu, and CD44	Prevented vaso-occlusion in SCD mice; tolerated in phase 1 and 2 human studies, with decrease in biomarkers of vasculopathy.^157,158
Phosphodiesterase-9 inhibitors (BAY73–6691, PF-04447943, IMR-687)	Vasodilates, anti-oxidant, anti- inflammatory	Decreased TNF and MPO, and increased SOD and NOX in sickle polymorphonuclear leukocytes²⁷⁹; decreased microvascular stasis in response to hypoxia/ reoxygenation in SCD mice^{111, 112}. Phase 1 completed (NCT02114203), no results available.
MEK inhibitors	Prevents activation of RBC and leukocyte adhesion molecules	Showed efficacy in animal models¹⁶⁰