title: Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates.
abstract: Bloodfeeding (hematophagous) parasites have evolved effective means of inhibiting mammalian thrombosis, thereby facilitating the acquisition and digestion of a bloodmeal. To date, specific inhibitors of coagulation and platelet function have been identified from numerous invertebrate species, representing an impressive array of convergent functional strategies. These parasite antithrombotics, in addition to playing a critical role in the diseases caused or transmitted by bloodfeeding invertebrates, may also serve as potentially useful therapeutic agents for the treatment of a variety of conditions associated with activation of thrombosis. A number of naturally occurring anticoagulants and platelet inhibitors have been evaluated in vivo, with some currently in varying stages of preclinical and clinical development. Because of the unique specificity and potency of parasite antithrombotics, these invertebrate natural products hold great promise for improving the treatment of a variety of human illnesses, including heart disease, stroke, and cancer.
authors.affiliation: L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06520, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Ledizet
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Harrison
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Koskia
authors.forename: Michael
authors.initials: M
authors.lastname: Cappello
mesh_terms: D000723:Ancylostomatoidea / Q000737:chemistry; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000627:therapeutic use; D001688:Biological Products / Q000302:isolation & purification* / Q000627:therapeutic use; D019774:Blood Coagulation Factor Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000627:therapeutic use; D006801:Humans; D007448:Invertebrates / Q000737:chemistry* / Q000502:physiology; D007865:Leeches / Q000737:chemistry; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control; D013987:Ticks / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D001688:Biological Products; D019774:Blood Coagulation Factor Inhibitors; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors