PMID- 26881476
OWN - NLM
STAT- MEDLINE
DCOM- 20161031
LR  - 20181113
IS  - 1744-7674 (Electronic)
IS  - 1354-3776 (Print)
IS  - 1354-3776 (Linking)
VI  - 26
IP  - 3
DP  - 2016
TI  - Factor XIa inhibitors: A review of the patent literature.
PG  - 323-45
LID - 10.1517/13543776.2016.1154045 [doi]
AB  - INTRODUCTION: Anticoagulants are the mainstay for prevention and/or treatment of 
      thrombotic disorders. Each clinically used anticoagulant is associated with 
      significant adverse consequences, especially bleeding. Factor XIa (FXIa), a key 
      factor involved in the amplification of procoagulation signal, has been suggested 
      as a major target for anticoagulant drug discovery because of reduced risk of 
      bleeding. AREAS COVERED: Our literature search uncovered dozens of industrial and 
      academic patents on the discovery of novel FXIa/FXI inhibitors. Small 
      peptidomimetics, sulfated glycosaminoglycan mimetics, polypeptides, antisense 
      oligonucleotides, and monoclonal antibodies have been developed as inhibitors of 
      FXIa. Although many agents are in early discovery/development phases, the 
      activity and safety of a few have been evaluated in various animal models and in 
      humans. EXPERT OPINION: FXIa is a promising drug target for development of 
      effective anticoagulants with limited bleeding complications. Literature reveals 
      a major trend in the number of patent applications over the last three years. 
      These inhibitors exploit different approaches for target inhibition. Allosteric 
      modulation of FXIa and biosynthetic inhibition of FXI are mechanistically unique. 
      Despite initial results in patients undergoing knee anthroplasty as with 
      antisense oligonucleotides, major advances should be realized, particularly with 
      respect to pharmacokinetics, for FXI/FXIa inhibitors to enter the clinic.
FAU - Al-Horani, Rami A
AU  - Al-Horani RA
AD  - a Department of Medicinal Chemistry & Institute for Structural Biology , Drug 
      Discovery and Development, Virginia Commonwealth University , Richmond , VA 23219 
      , USA.
FAU - Desai, Umesh R
AU  - Desai UR
AD  - a Department of Medicinal Chemistry & Institute for Structural Biology , Drug 
      Discovery and Development, Virginia Commonwealth University , Richmond , VA 23219 
      , USA.
LA  - eng
GR  - R01 HL090586/HL/NHLBI NIH HHS/United States
GR  - HL090586/HL/NHLBI NIH HHS/United States
GR  - R25 HL128639/HL/NHLBI NIH HHS/United States
GR  - P01 HL107152/HL/NHLBI NIH HHS/United States
GR  - HL128639/HL/NHLBI NIH HHS/United States
GR  - HL107152/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - England
TA  - Expert Opin Ther Pat
JT  - Expert opinion on therapeutic patents
JID - 9516419
RN  - 0 (Anticoagulants)
RN  - EC 3.4.21.27 (Factor XIa)
SB  - IM
MH  - Animals
MH  - Anticoagulants/adverse effects/pharmacokinetics/*pharmacology
MH  - *Drug Design
MH  - Factor XIa/*antagonists & inhibitors
MH  - Hemorrhage/chemically induced
MH  - Humans
MH  - Patents as Topic
MH  - Thrombosis/drug therapy
PMC - PMC4941829
MID - NIHMS799442
OTO - NOTNLM
OT  - FXI/FXIa
OT  - active site inhibitors
OT  - allosteric inhibitors
OT  - antisense oligonucleotides
OT  - drug discovery
OT  - enzyme inhibition
OT  - monoclonal antibodies
OT  - polypeptides
OT  - safe anticoagulant
OT  - thrombosis
EDAT- 2016/02/18 06:00
MHDA- 2016/11/01 06:00
PMCR- 2017/01/01
CRDT- 2016/02/17 06:00
PHST- 2016/02/17 06:00 [entrez]
PHST- 2016/02/18 06:00 [pubmed]
PHST- 2016/11/01 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.1517/13543776.2016.1154045 [doi]
PST - ppublish
SO  - Expert Opin Ther Pat. 2016;26(3):323-45. doi: 10.1517/13543776.2016.1154045.