M-118, a novel, low-molecular-weight heparin for the potential treatment of cardiovascular disorders.
Safe inhibition of thrombosis is a key therapeutic strategy in modern cardiovascular medicine, and both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are commonly used in clinical practice. However, both have several drawbacks, such as the unpredictable pharmacokinetics of UFH and the non-reversibility of LMWH. M-118, being developed by Momenta Pharmaceuticals Inc, is a novel LMWH that has been engineered to overcome the drawbacks of UFH and currently available LMWHs, while maintaining their beneficial attributes. In preclinical studies and phase I clinical trials, M-118 demonstrated potent activity against thrombin and Factor Xa, which could be reversed with protamine; M-118 also demonstrated a high and predictable bioavailability, and a short half-life. Promising results were observed in a phase II clinical trial in patients undergoing coronary interventions, although phase III clinical trials are required to establish the role for M-118 in contemporary medicine.
Shah
Hriday
H
University of Michigan, Division of Cardiovascular Medicine, 2A394, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5853, USA.
Gurm
Hitinder S
HS
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011817:Rabbits; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000188:drug therapy
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; C555479:M-118 compound; D013917:Thrombin